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Xu R, Ooi HS, Bian L, Ouyang L, Sun W. Dynamic hydrogels for biofabrication: A review. Biomaterials 2025; 320:123266. [PMID: 40120174 DOI: 10.1016/j.biomaterials.2025.123266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 03/06/2025] [Accepted: 03/17/2025] [Indexed: 03/25/2025]
Abstract
Reversibly crosslinked dynamic hydrogels have emerged as a significant material platform for biomedical applications owing to their distinctive time-dependent characteristics, including shear-thinning, self-healing, stress relaxation, and creep. These physical properties permit the use of dynamic hydrogels as injectable carriers or three-dimensional printable bioinks. It is noteworthy that matrix dynamics can serve as physical cues that stimulate cellular processes. Therefore, dynamic hydrogels are preferred for tissue engineering and biofabrication, which seek to create functional tissue constructs that require regulation of cellular processes. This review summarizes the critical biophysical properties of dynamic hydrogels, various cellular processes and related mechanisms triggered by hydrogel dynamics, particularly in three-dimensional culture scenarios. Subsequently, we present an overview of advanced biofabrication techniques, particularly 3D bioprinting, of dynamic hydrogels for the large-scale production of tissue and organ engineering models. This review presents an overview of the strategies that can be used to expand the range of applications of dynamic hydrogels in biofabrication, while also addressing the challenges and opportunities that arise in the field. This review highlights the importance of matrix dynamics in regulating cellular processes and elucidates strategies for leveraging them in the context of biofabrication.
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Affiliation(s)
- Runze Xu
- Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base), Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China
| | - Hon Son Ooi
- Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base), Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China
| | - Liming Bian
- School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 511442, China
| | - Liliang Ouyang
- Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base), Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China; State Key Laboratory of Tribology in Advanced Equipment, Tsinghua University, Beijing, 100084, China.
| | - Wei Sun
- Biomanufacturing and Engineering Living Systems Innovation International Talents Base (111 Base), Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China; Department of Mechanical Engineering and Mechanics, Drexel University, Philadelphia, PA, 19104, USA
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2
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Wang Y, Chen S, Lu Z, Liu Y, Hu J, Zhou D. Inferring absolute cell numbers from relative proportion in stochastic models with cell plasticity. J Theor Biol 2025; 608:112133. [PMID: 40280232 DOI: 10.1016/j.jtbi.2025.112133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 04/13/2025] [Accepted: 04/18/2025] [Indexed: 04/29/2025]
Abstract
Quantifying dynamic changes in cell populations is crucial for a comprehensive understanding of biological processes such as cell proliferation, injury repair, and disease progression. However, compared to directly measuring the absolute cell numbers of specific subpopulations, relative proportion data demonstrate greater reproducibility and yield more stable, reliable outcomes. Therefore, inferring absolute cell numbers from relative proportion data may present a novel approach for effectively predicting changes in cell population sizes. To address this, we establish two mathematical mappings between cell proportions and population sizes using moment equations derived from stochastic cell-plasticity models. Notably, our findings indicate that one of these mappings does not require prior knowledge of the initial population size, highlighting the value of incorporating variance information into cell proportion data. We evaluated the robustness of our methods from multiple perspectives and extended their application to various biological mechanisms within the context of cell plasticity models. These methods help mitigate the limitations associated with the direct measurement of absolute cell counts through experimental techniques. Moreover, they provide new insights into leveraging the stochastic dynamics of cell populations to quantify interactions between different biomasses within the system.
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Affiliation(s)
- Yuman Wang
- School of Mathematical Sciences, Xiamen University, Xiamen, 361005, PR China; National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, 361005, PR China
| | - Shuli Chen
- School of Mathematics, Sun Yat-sen University, Guangdong, 510275, PR China
| | - Zhaolian Lu
- Shenzhen Institute of Advanced Technology, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Chinese Academy of Sciences, Shenzhen, PR China
| | - Yu Liu
- Department of Systems Science, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, 519087, PR China; International Academic Center of Complex Systems, Beijing Normal University, Zhuhai, 519087, PR China
| | - Jie Hu
- School of Mathematical Sciences, Xiamen University, Xiamen, 361005, PR China; National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, 361005, PR China.
| | - Da Zhou
- School of Mathematical Sciences, Xiamen University, Xiamen, 361005, PR China; National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, 361005, PR China.
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3
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Fazeli MA, Amiri M, Rostaminasab G, Akbaripour V, Mikaeili A, Othman M, Rezakhani L. Application of decellularized tissues in ear regeneration. J Tissue Viability 2025; 34:100870. [PMID: 39970482 DOI: 10.1016/j.jtv.2025.100870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 01/15/2025] [Accepted: 02/07/2025] [Indexed: 02/21/2025]
Abstract
More than 5 % of people worldwide suffer from hearing disorders. Ototoxic drugs, aging, exposure to loud sounds, rupture, subperichondrial hematoma, perichondritis, burns and frostbite and infections are the main causes of hearing loss, some of which can destroy the cartilage and lead to deformation. On the other hand, disorders of the external ear are diverse and can range from dangerous neoplasms to defects that are not acceptable from a cosmetic standpoint. These issues include injuries, blockages, dermatoses, and infections, and any or all of them may be bothersome to the busy doctor. Using an implant or hearing aid is one of the treatment strategies for deafness. However, these medical devices are not useful for every eligible patient. With the right therapy, many of these issues are not life-threatening and can be treated with confidence in a positive outcome. As medical research and treatment have advanced dramatically in the past ten years, tissue engineering (TE) has emerged as a promising method to regenerate damaged tissue, raising the prospect of a permanent cure for deafness. Decellularization is now seen as a promising development for regenerative medicine, and an increasing number of applications are being found for acellular matrices. Studies on decellularization show that natural scaffolds made from decellularized tissues can serve as a suitable platform while preserving the main components, and the preparation of such scaffolds will be an important part of future bioscience research. It can have wide applications in regenerative medicine and TE. This review intends to give an overview of the status of research and alternative scaffolds in inner and outer ear regenerative medicine from both a preclinical and clinical perspective for ear disorders in order to show how ongoing TE research has the potential to advance and enhance novel disease treatments.
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Affiliation(s)
- Manouchehr Avatef Fazeli
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Masoumeh Amiri
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Gelavizh Rostaminasab
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Vahid Akbaripour
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Abdolhamid Mikaeili
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Othman
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Leila Rezakhani
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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4
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Canosa S, Silvestris E, Carosso AR, Ruffa A, Evangelisti B, Gennarelli G, Cormio G, Loizzi V, Rolfo A, Benedetto C, Revelli A. Ovarian Stem Cells: Will the Dream of Neo-Folliculogenesis After Birth Become Real? Obstet Gynecol Surv 2025; 80:112-120. [PMID: 39924337 DOI: 10.1097/ogx.0000000000001360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2025]
Abstract
Importance Ovarian stem cells (OSCs) represent a promising tool in reproductive medicine, particularly for the treatment of premature ovarian failure and fertility preservation. Objectives Herein, we summarize the main characteristics of adult stem cells, their status, needs, and new challenges in the application in reproductive medicine. Evidence Acquisition Clinical studies have shown that OSCs transplantation can restore ovarian function and stimulate neo-folliculogenesis in patients with premature ovarian failure, enabling them to conceive naturally or through in vitro fertilization techniques. Moreover, OSCs gained increasing interest as a chance to preserve fertility in cancer patients undergoing gonadotoxic treatments affecting their fertility, as chemotherapy or radiotherapy. Results The recruitment of OSCs from fresh or thawed ovarian fragments coupled with their capability to differentiate in vitro to mature oocytes could provide a novel opportunity to verify their suitability to be expanded in vitro as oocyte like cells. Conclusions and Relevance Research into OSCs and their applications in reproductive medicine is still in its infancy, but the results so far are promising and offer new possibilities for patients suffering from premature ovarian failure or cancer.
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Affiliation(s)
- Stefano Canosa
- Obstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, Department of Surgical Sciences, Sant'Anna Hospital, University of Turin, Turin, Italy
| | - Erica Silvestris
- Gynecologic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II," Bari, Italy
| | - Andrea Roberto Carosso
- Obstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, Department of Surgical Sciences, Sant'Anna Hospital, University of Turin, Turin, Italy
| | - Alessandro Ruffa
- Obstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, Department of Surgical Sciences, Sant'Anna Hospital, University of Turin, Turin, Italy
| | - Bernadette Evangelisti
- Obstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, Department of Surgical Sciences, Sant'Anna Hospital, University of Turin, Turin, Italy
| | - Gianluca Gennarelli
- Obstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, Department of Surgical Sciences, Sant'Anna Hospital, University of Turin, Turin, Italy
| | - Gennaro Cormio
- Gynecologic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II," Bari, Italy; Department of Interdisciplinary Medicine, University of Bari "Aldo Moro," Bari, Italy
| | - Vera Loizzi
- Gynecologic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II," Bari, Italy; Department of Interdisciplinary Medicine, University of Bari "Aldo Moro," Bari, Italy
| | - Alessandro Rolfo
- Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Chiara Benedetto
- Obstetrics and Gynecology 1U, Physiopathology of Reproduction and IVF Unit, Department of Surgical Sciences, Sant'Anna Hospital, University of Turin, Turin, Italy
| | - Alberto Revelli
- Gynecology and Obstetrics 2U, Department of Surgical Sciences, S. Anna Hospital, University of Turin, Turin, Italy
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Li N, Du X, Zhao Y, Zeng Q, Han C, Xiong D, He L, Zhang G, Liu W. Exploring stem cell technology: Pioneering new pathways for female fertility preservation and restoration. Reprod Biol 2024; 24:100958. [PMID: 39393314 DOI: 10.1016/j.repbio.2024.100958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 09/24/2024] [Accepted: 09/28/2024] [Indexed: 10/13/2024]
Abstract
The fertility of women is crucial for the well-being of individuals and families. However, various factors such as chemotherapy, lifestyle changes, among others, may lead to a decline in female fertility, thus emphasizing the significance of preserving and restoring fertility. Stem cells, with their unique capacity for self-renewal and pluripotent differentiation, have made significant strides in areas such as ovarian tissue cryopreservation, in vitro culture of frozen-thawed ovarian tissue, and construction of ovarian-like organs. This review aims to summarize the latest findings in these fields, highlighting the pivotal role, mechanisms, and future prospects of stem cell technology in preserving and restoring female fertility. Additionally, the importance of interdisciplinary collaboration is underscored, as personalized stem cell therapy regimens tailored through interdisciplinary cooperation between reproductive medicine and stem cell fields hold promise in providing reliable solutions for the preservation and restoration of female fertility.
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Affiliation(s)
- Ningjing Li
- School of Medicine and life sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xinrong Du
- School of Medicine and life sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yuhong Zhao
- College of Laboratory Medicine, Chengdu Medical College, Chengdu 610500, China
| | - Qin Zeng
- Sichuan Provincial Woman's and Children's Hospital / The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu 610045, China
| | - Changli Han
- School of Medicine and life sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Dongsheng Xiong
- Sichuan Provincial Woman's and Children's Hospital / The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu 610045, China
| | - Libing He
- Sichuan Provincial Woman's and Children's Hospital / The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu 610045, China
| | - Guohui Zhang
- Sichuan Provincial Woman's and Children's Hospital / The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu 610045, China.
| | - Weixin Liu
- Sichuan Provincial Woman's and Children's Hospital / The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu 610045, China.
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6
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Nureen L, Di Girolamo N. A Simple Method to Dissect, Orientate, and Visualize the Murine Limbal Stem Cell Niche with Cornea and Conjunctiva Attached. Methods Mol Biol 2024. [PMID: 39570549 DOI: 10.1007/7651_2024_577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2024]
Abstract
The limbus is a narrow tissue intersection between the cornea and conjunctiva which is purported to harbor stem cells (SCs) that replenish the corneal epithelium throughout life. Damage to these cells can result in debilitating visual consequences. To date, various immunohistochemical methods have been employed to investigate limbal morphology and identify SC location to improve their isolation for therapeutic use. However, none of these methods preserve tissue integrity and orientation, nor do they incorporate adjacent conjunctiva as a contiguous ocular surface for analyses. In this chapter, we provide a methodology to overcome these limitations by integrating a unique dissection technique along with a tissue clearing strategy to enable the detection of morphological features within the limbal SC niche in different locations across its circumference. The morphological and biochemical details acquired from such investigations will heighten the current understanding of changes in tissue architecture in healthy and diseased corneas and in those that have been treated with biologicals, pharmacological, and/or surgical interventions.
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Affiliation(s)
- Lamia Nureen
- School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
| | - Nick Di Girolamo
- School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
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7
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Brien H, Lee JC, Sharma J, Hamann CA, Spetz MR, Lippmann ES, Brunger JM. Templated Pluripotent Stem Cell Differentiation via Substratum-Guided Artificial Signaling. ACS Biomater Sci Eng 2024; 10:6465-6482. [PMID: 39352143 PMCID: PMC11480943 DOI: 10.1021/acsbiomaterials.4c00885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 09/20/2024] [Accepted: 09/24/2024] [Indexed: 10/15/2024]
Abstract
The emerging field of synthetic morphogenesis implements synthetic biology tools to investigate the minimal cellular processes sufficient for orchestrating key developmental events. As the field continues to grow, there is a need for new tools that enable scientists to uncover nuances in the molecular mechanisms driving cell fate patterning that emerge during morphogenesis. Here, we present a platform that combines cell engineering with biomaterial design to potentiate artificial signaling in pluripotent stem cells (PSCs). This platform, referred to as PSC-MATRIX, extends the use of programmable biomaterials to PSCs competent to activate morphogen production through orthogonal signaling, giving rise to the opportunity to probe developmental events by initiating morphogenetic programs in a spatially constrained manner through non-native signaling channels. We show that the PSC-MATRIX platform enables temporal and spatial control of transgene expression in response to bulk, soluble inputs in synthetic Notch (synNotch)-engineered human PSCs for an extended culture of up to 11 days. Furthermore, we used PSC-MATRIX to regulate multiple differentiation events via material-mediated artificial signaling in engineered PSCs using the orthogonal ligand green fluorescent protein, highlighting the potential of this platform for probing and guiding fate acquisition. Overall, this platform offers a synthetic approach to interrogate the molecular mechanisms driving PSC differentiation that could be applied to a variety of differentiation protocols.
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Affiliation(s)
- Hannah
J. Brien
- Department
of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States
| | - Joanne C. Lee
- Department
of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States
| | - Jhanvi Sharma
- Department
of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States
| | - Catherine A. Hamann
- Department
of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States
| | - Madeline R. Spetz
- Department
of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States
| | - Ethan S. Lippmann
- Department
of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States
- Center
for Stem Cell Biology, Vanderbilt University, Nashville, Tennessee 37235, United States
| | - Jonathan M. Brunger
- Department
of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States
- Center
for Stem Cell Biology, Vanderbilt University, Nashville, Tennessee 37235, United States
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Sun B, Cheng X, Wu Q. The Endometrial Stem/Progenitor Cells and Their Niches. Stem Cell Rev Rep 2024; 20:1273-1284. [PMID: 38635126 DOI: 10.1007/s12015-024-10725-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/10/2024] [Indexed: 04/19/2024]
Abstract
Endometrial stem/progenitor cells are a type of stem cells with the ability to self-renew and differentiate into multiple cell types. They exist in the endometrium and form niches with their neighbor cells and extracellular matrix. The interaction between endometrial stem/progenitor cells and niches plays an important role in maintaining, repairing, and regenerating the endometrial structure and function. This review will discuss the characteristics and functions of endometrial stem/progenitor cells and their niches, the mechanisms of their interaction, and their roles in endometrial regeneration and diseases. Finally, the prospects for their applications will also be explored.
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Affiliation(s)
- Baolan Sun
- Department of Clinical Laboratory, Affiliated Hospital of Nantong University, Nantong, China.
- The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
| | - Xi Cheng
- Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, China
| | - Qiang Wu
- Department of Clinical Laboratory, Affiliated Hospital of Nantong University, Nantong, China.
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Guo S, Wang D. Novel insights into the potential applications of stem cells in pulmonary hypertension therapy. Respir Res 2024; 25:237. [PMID: 38849894 PMCID: PMC11162078 DOI: 10.1186/s12931-024-02865-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 06/04/2024] [Indexed: 06/09/2024] Open
Abstract
Pulmonary hypertension (PH) refers to a group of deadly lung diseases characterized by vascular lesions in the microvasculature and a progressive increase in pulmonary vascular resistance. The prevalence of PH has increased over time. Currently, the treatment options available for PH patients have limited efficacy, and none of them can fundamentally reverse pulmonary vascular remodeling. Stem cells represent an ideal seed with proven efficacy in clinical studies focusing on liver, cardiovascular, and nerve diseases. Since the potential therapeutic effect of mesenchymal stem cells (MSCs) on PH was first reported in 2006, many studies have demonstrated the efficacy of stem cells in PH animal models and suggested that stem cells can help slow the deterioration of lung tissue. Existing PH treatment studies basically focus on the paracrine action of stem cells, including protein regulation, exosome pathway, and cell signaling; however, the specific mechanisms have not yet been clarified. Apoptotic and afunctional pulmonary microvascular endothelial cells (PMVECs) and alveolar epithelial cells (AECs) are two fundamental promoters of PH although they have not been extensively studied by researchers. This review mainly focuses on the supportive communication and interaction between PMVECs and AECs as well as the potential restorative effect of stem cells on their injury. In the future, more studies are needed to prove these effects and explore more radical cures for PH.
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Affiliation(s)
- Sijia Guo
- Stem Cell Laboratory, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
| | - Dachun Wang
- Stem Cell Laboratory, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
- The Brown Foundation Institute of Molecular Medicine for the prevention of Human Diseases, University of Texas Medical School at Houston, Houston, TX, USA
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Pasquariello R, Bogliolo L, Di Filippo F, Leoni GG, Nieddu S, Podda A, Brevini TAL, Gandolfi F. Use of assisted reproductive technologies (ARTs) to shorten the generational interval in ruminants: current status and perspectives. Theriogenology 2024; 225:16-32. [PMID: 38788626 DOI: 10.1016/j.theriogenology.2024.05.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 05/18/2024] [Accepted: 05/18/2024] [Indexed: 05/26/2024]
Abstract
The challenges posed by climate change and increasing world population are stimulating renewed efforts for improving the sustainability of animal production. To meet such challenges, the contribution of genomic selection approaches, in combination with assisted reproductive technologies (ARTs), to spreading and preserving animal genetics is essential. The largest increase in genetic gain can be achieved by shortening the generation interval. This review provides an overview of the current status and progress of advanced ARTs that could be applied to reduce the generation time in both female and male of domestic ruminants. In females, the use of juvenile in vitro embryo transfer (JIVET) enables to generate offspring after the transfer of in vitro produced embryos derived from oocytes of prepubertal genetically superior donors reducing the generational interval and acceleration genetic gain. The current challenge is increasing in vitro embryo production (IVEP) from prepubertal derived oocytes which is still low and variable. The two main factors limiting IVEP success are the intrinsic quality of prepubertal oocytes and the culture systems for in vitro maturation (IVM). In males, advancements in ARTs are providing new strategies to in vitro propagate spermatogonia and differentiate them into mature sperm or even to recapitulate the whole process of spermatogenesis from embryonic stem cells. Moreover, the successful use of immature cells, such as round spermatids, for intracytoplasmic injection (ROSI) and IVEP could allow to complete the entire process in few months. However, these approaches have been successfully applied to human and mouse whereas only a few studies have been published in ruminants and results are still controversial. This is also dependent on the efficiency of ROSI that is limited by the current isolation and selection protocols of round spermatids. In conclusion, the current efforts for improving these reproductive methodologies could lead toward a significant reduction of the generational interval in livestock animals that could have a considerable impact on agriculture sustainability.
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Affiliation(s)
- Rolando Pasquariello
- Department of Agricultural and Environmental Sciences, University of Milan, Milano, Italy
| | - Luisa Bogliolo
- Department of Veterinary Medicine, University of Sassari, Sassari, Italy
| | - Francesca Di Filippo
- Department of Agricultural and Environmental Sciences, University of Milan, Milano, Italy
| | | | - Stefano Nieddu
- Department of Veterinary Medicine, University of Sassari, Sassari, Italy
| | - Andrea Podda
- Department of Veterinary Medicine, University of Sassari, Sassari, Italy
| | - Tiziana A L Brevini
- Laboratory of Biomedical Embryology and Tissue Engineering, Department of Veterinary Medicine and Animal Science, University of Milan, Lodi, Italy
| | - Fulvio Gandolfi
- Department of Agricultural and Environmental Sciences, University of Milan, Milano, Italy.
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11
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Shi Y, Yang X, Min J, Kong W, Hu X, Zhang J, Chen L. Advancements in culture technology of adipose-derived stromal/stem cells: implications for diabetes and its complications. Front Endocrinol (Lausanne) 2024; 15:1343255. [PMID: 38681772 PMCID: PMC11045945 DOI: 10.3389/fendo.2024.1343255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 03/29/2024] [Indexed: 05/01/2024] Open
Abstract
Stem cell-based therapies exhibit considerable promise in the treatment of diabetes and its complications. Extensive research has been dedicated to elucidate the characteristics and potential applications of adipose-derived stromal/stem cells (ASCs). Three-dimensional (3D) culture, characterized by rapid advancements, holds promise for efficacious treatment of diabetes and its complications. Notably, 3D cultured ASCs manifest enhanced cellular properties and functions compared to traditional monolayer-culture. In this review, the factors influencing the biological functions of ASCs during culture are summarized. Additionally, the effects of 3D cultured techniques on cellular properties compared to two-dimensional culture is described. Furthermore, the therapeutic potential of 3D cultured ASCs in diabetes and its complications are discussed to provide insights for future research.
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Affiliation(s)
- Yinze Shi
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Xueyang Yang
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Jie Min
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Wen Kong
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Xiang Hu
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Jiaoyue Zhang
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
| | - Lulu Chen
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China
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12
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Parigini C, Greulich P. Homeostatic regulation of renewing tissue cell populations via crowding control: stability, robustness and quasi-dedifferentiation. J Math Biol 2024; 88:47. [PMID: 38520536 PMCID: PMC10960778 DOI: 10.1007/s00285-024-02057-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 01/18/2024] [Accepted: 01/28/2024] [Indexed: 03/25/2024]
Abstract
To maintain renewing epithelial tissues in a healthy, homeostatic state, cell divisions and differentiation need to be tightly regulated. Mechanisms of homeostatic regulation often rely on crowding feedback control: cells are able to sense the cell density in their environment, via various molecular and mechanosensing pathways, and respond by adjusting division, differentiation, and cell state transitions appropriately. Here, we determine, via a mathematically rigorous framework, which general conditions for the crowding feedback regulation (i) must be minimally met, and (ii) are sufficient, to allow the maintenance of homeostasis in renewing tissues. We show that those conditions naturally allow for a degree of robustness toward disruption of regulation. Furthermore, intrinsic to this feedback regulation is that stem cell identity is established collectively by the cell population, not by individual cells, which implies the possibility of 'quasi-dedifferentiation', in which cells committed to differentiation may reacquire stem cell properties upon depletion of the stem cell pool. These findings can guide future experimental campaigns to identify specific crowding feedback mechanisms.
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Affiliation(s)
- Cristina Parigini
- School of Mathematical Sciences, University of Southampton, Southampton, UK
- Institute for Life Sciences, University of Southampton, Southampton, UK
- Te Pūnaha Ātea - Space Institute, University of Auckland, Auckland, New Zealand
| | - Philip Greulich
- School of Mathematical Sciences, University of Southampton, Southampton, UK.
- Institute for Life Sciences, University of Southampton, Southampton, UK.
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13
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Smandri A, Al-Masawa ME, Hwei NM, Fauzi MB. ECM-derived biomaterials for regulating tissue multicellularity and maturation. iScience 2024; 27:109141. [PMID: 38405613 PMCID: PMC10884934 DOI: 10.1016/j.isci.2024.109141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2024] Open
Abstract
Recent breakthroughs in developing human-relevant organotypic models led to the building of highly resemblant tissue constructs that hold immense potential for transplantation, drug screening, and disease modeling. Despite the progress in fine-tuning stem cell multilineage differentiation in highly controlled spatiotemporal conditions and hosting microenvironments, 3D models still experience naive and incomplete morphogenesis. In particular, existing systems and induction protocols fail to maintain stem cell long-term potency, induce high tissue-level multicellularity, or drive the maturity of stem cell-derived 3D models to levels seen in their in vivo counterparts. In this review, we highlight the use of extracellular matrix (ECM)-derived biomaterials in providing stem cell niche-mimicking microenvironment capable of preserving stem cell long-term potency and inducing spatial and region-specific differentiation. We also examine the maturation of different 3D models, including organoids, encapsulated in ECM biomaterials and provide looking-forward perspectives on employing ECM biomaterials in building more innovative, transplantable, and functional organs.
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Affiliation(s)
- Ali Smandri
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Maimonah Eissa Al-Masawa
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Ng Min Hwei
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Mh Busra Fauzi
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
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14
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Shivaramu S, Maiti SK, Banu SA, Kalaiselvan E, Sharun K, Mishra M, Mohan D, Palakkara S, Kumar S, Sahoo M, Hescheler J. Synergistic Hepatoprotective Effects of Mesenchymal Stem Cells and Platelet-Rich Plasma in a Rat Model of Bile Duct Ligation-Induced Liver Cirrhosis. Cells 2024; 13:404. [PMID: 38474368 PMCID: PMC10931218 DOI: 10.3390/cells13050404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 02/10/2024] [Accepted: 02/22/2024] [Indexed: 03/14/2024] Open
Abstract
Liver cirrhosis poses a global health challenge marked by significant prevalence and mortality. Current therapeutic options are limited by high costs and immune-mediated rejection, necessitating the exploration of innovative strategies to enhance hepatic self-rehabilitation, and counteract the underlying pathological mechanisms. We evaluated the hepatoprotective activity of rat adipose-derived mesenchymal stem cells (ADMSCs) in combination with platelet-rich plasma (PRP) and recombinant human hepatocyte growth factor (rh-HGF) on a rat model of liver fibrosis/cirrhosis induced by bile duct ligation (BDL). Treatment with PRP or rh-HGF alone did not yield significant hepatoprotection in the BDL-induced liver cirrhosis model. However, ADMSC transplantation alone exhibited the potential to alleviate impaired liver conditions. The combination of PRP and rh-HGF demonstrated superior ameliorative effects compared to either treatment alone. Notably, the combination of ADMSC + PRP or ADMSC + rh-HGF significantly enhanced hepatoprotective capacity compared to individual or combined PRP and rh-HGF therapies. Injection of ADMSC via the tail vein reduced inflammation, hepatocyte damage, and collagen deposition, improving overall liver function. This improvement was more pronounced when ADMSC was administered with PRP and rh-HGF versus monotherapy. Our study concludes that ADMSCs exert antifibrotic effects by inhibiting hepatic stellate cell proliferation, collagen synthesis, and inducing apoptosis. ADMSCs also demonstrate immune-modulatory effects and transdifferentiate into hepatic progenitor cells, secreting trophic factors, cytokines, and chemokines that promote impaired liver regeneration. The observed arrest in liver fibrosis progression highlights the potential therapeutic impact of these interventions.
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Affiliation(s)
- Shivaraju Shivaramu
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Swapan Kumar Maiti
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Shajahan Amitha Banu
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Elangovan Kalaiselvan
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Khan Sharun
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
- Graduate Institute of Medicine, Yuan Ze University, Taoyuan 32003, Taiwan
| | - Mamta Mishra
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Divya Mohan
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Sangeetha Palakkara
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India; (S.S.); (S.A.B.); (E.K.); (K.S.); (M.M.); (D.M.); (S.P.)
| | - Sunil Kumar
- Division of Extension Education, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India;
| | - Monalisa Sahoo
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India;
| | - Jürgen Hescheler
- Institute of Neurophysiology, University of Cologne, 50931 Cologne, Germany;
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15
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Lee G, Han SB, Kim SH, Jeong S, Kim DH. Stretching of porous poly (l-lactide-co-ε-caprolactone) membranes regulates the differentiation of mesenchymal stem cells. Front Cell Dev Biol 2024; 12:1303688. [PMID: 38333594 PMCID: PMC10850303 DOI: 10.3389/fcell.2024.1303688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 01/12/2024] [Indexed: 02/10/2024] Open
Abstract
Background: Among a variety of biomaterials supporting cell growth for therapeutic applications, poly (l-lactide-co-ε-caprolactone) (PLCL) has been considered as one of the most attractive scaffolds for tissue engineering owing to its superior mechanical strength, biocompatibility, and processibility. Although extensive studies have been conducted on the relationship between the microstructure of polymeric materials and their mechanical properties, the use of the fine-tuned morphology and mechanical strength of PLCL membranes in stem cell differentiation has not yet been studied. Methods: PLCL membranes were crystallized in a combination of diverse solvent-nonsolvent mixtures, including methanol (MeOH), isopropanol (IPA), chloroform (CF), and distilled water (DW), with different solvent polarities. A PLCL membrane with high mechanical strength induced by limited pore formation was placed in a custom bioreactor mimicking the reproducible physiological microenvironment of the vascular system to promote the differentiation of mesenchymal stem cells (MSCs) into smooth muscle cells (SMCs). Results: We developed a simple, cost-effective method for fabricating porosity-controlled PLCL membranes based on the crystallization of copolymer chains in a combination of solvents and non-solvents. We confirmed that an increase in the ratio of the non-solvent increased the chain aggregation of PLCL by slow evaporation, leading to improved mechanical properties of the PLCL membrane. Furthermore, we demonstrated that the cyclic stretching of PLCL membranes induced MSC differentiation into SMCs within 10 days of culture. Conclusion: The combination of solvent and non-solvent casting for PLCL solidification can be used to fabricate mechanically durable polymer membranes for use as mechanosensitive scaffolds for stem cell differentiation.
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Affiliation(s)
- Geonhui Lee
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, United States
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States
| | - Seong-Beom Han
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea
| | - Soo Hyun Kim
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, Republic of Korea
| | - Sangmoo Jeong
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, United States
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States
| | - Dong-Hwee Kim
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul, Republic of Korea
- Department of Integrative Energy Engineering, College of Engineering, Korea University, Seoul, Republic of Korea
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16
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Khorasani N, Sadeghi M. A computational model of stem cells' internal mechanism to recapitulate spatial patterning and maintain the self-organized pattern in the homeostasis state. Sci Rep 2024; 14:1528. [PMID: 38233402 PMCID: PMC10794714 DOI: 10.1038/s41598-024-51386-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 01/04/2024] [Indexed: 01/19/2024] Open
Abstract
The complex functioning of multi-cellular tissue development relies on proper cell production rates to replace dead or differentiated specialized cells. Stem cells are critical for tissue development and maintenance, as they produce specialized cells to meet the tissues' demands. In this study, we propose a computational model to investigate the stem cell's mechanism, which generates the appropriate proportion of specialized cells, and distributes them to their correct position to form and maintain the organized structure in the population through intercellular reactions. Our computational model focuses on early development, where the populations overall behavior is determined by stem cells and signaling molecules. The model does not include complicated factors such as movement of specialized cells or outside signaling sources. The results indicate that in our model, the stem cells can organize the population into a desired spatial pattern, which demonstrates their ability to self-organize as long as the corresponding leading signal is present. We also investigate the impact of stochasticity, which provides desired non-genetic diversity; however, it can also break the proper boundaries of the desired spatial pattern. We further examine the role of the death rate in maintaining the system's steady state. Overall, our study sheds light on the strategies employed by stem cells to organize specialized cells and maintain proper functionality. Our findings provide insight into the complex mechanisms involved in tissue development and maintenance, which could lead to new approaches in regenerative medicine and tissue engineering.
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Affiliation(s)
- Najme Khorasani
- School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.
| | - Mehdi Sadeghi
- National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
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17
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Velikic G, Maric DM, Maric DL, Supic G, Puletic M, Dulic O, Vojvodic D. Harnessing the Stem Cell Niche in Regenerative Medicine: Innovative Avenue to Combat Neurodegenerative Diseases. Int J Mol Sci 2024; 25:993. [PMID: 38256066 PMCID: PMC10816024 DOI: 10.3390/ijms25020993] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 11/30/2023] [Accepted: 12/06/2023] [Indexed: 01/24/2024] Open
Abstract
Regenerative medicine harnesses the body's innate capacity for self-repair to restore malfunctioning tissues and organs. Stem cell therapies represent a key regenerative strategy, but to effectively harness their potential necessitates a nuanced understanding of the stem cell niche. This specialized microenvironment regulates critical stem cell behaviors including quiescence, activation, differentiation, and homing. Emerging research reveals that dysfunction within endogenous neural stem cell niches contributes to neurodegenerative pathologies and impedes regeneration. Strategies such as modifying signaling pathways, or epigenetic interventions to restore niche homeostasis and signaling, hold promise for revitalizing neurogenesis and neural repair in diseases like Alzheimer's and Parkinson's. Comparative studies of highly regenerative species provide evolutionary clues into niche-mediated renewal mechanisms. Leveraging endogenous bioelectric cues and crosstalk between gut, brain, and vascular niches further illuminates promising therapeutic opportunities. Emerging techniques like single-cell transcriptomics, organoids, microfluidics, artificial intelligence, in silico modeling, and transdifferentiation will continue to unravel niche complexity. By providing a comprehensive synthesis integrating diverse views on niche components, developmental transitions, and dynamics, this review unveils new layers of complexity integral to niche behavior and function, which unveil novel prospects to modulate niche function and provide revolutionary treatments for neurodegenerative diseases.
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Affiliation(s)
- Gordana Velikic
- Department for Research and Development, Clinic Orto MD-Parks Dr. Dragi Hospital, 21000 Novi Sad, Serbia
- Hajim School of Engineering, University of Rochester, Rochester, NY 14627, USA
| | - Dusan M. Maric
- Department for Research and Development, Clinic Orto MD-Parks Dr. Dragi Hospital, 21000 Novi Sad, Serbia
- Faculty of Stomatology Pancevo, University Business Academy, 26000 Pancevo, Serbia;
| | - Dusica L. Maric
- Department of Anatomy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia
| | - Gordana Supic
- Institute for Medical Research, Military Medical Academy, 11000 Belgrade, Serbia; (G.S.); (D.V.)
- Medical Faculty of Military Medical Academy, University of Defense, 11000 Belgrade, Serbia
| | - Miljan Puletic
- Faculty of Stomatology Pancevo, University Business Academy, 26000 Pancevo, Serbia;
| | - Oliver Dulic
- Department of Surgery, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Danilo Vojvodic
- Institute for Medical Research, Military Medical Academy, 11000 Belgrade, Serbia; (G.S.); (D.V.)
- Medical Faculty of Military Medical Academy, University of Defense, 11000 Belgrade, Serbia
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18
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Nureen L, Di Girolamo N. Limbal Epithelial Stem Cells in the Diabetic Cornea. Cells 2023; 12:2458. [PMID: 37887302 PMCID: PMC10605319 DOI: 10.3390/cells12202458] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/10/2023] [Accepted: 10/11/2023] [Indexed: 10/28/2023] Open
Abstract
Continuous replenishment of the corneal epithelium is pivotal for maintaining optical transparency and achieving optimal visual perception. This dynamic process is driven by limbal epithelial stem cells (LESCs) located at the junction between the cornea and conjunctiva, which is otherwise known as the limbus. In patients afflicted with diabetes, hyperglycemia-induced impairments in corneal epithelial regeneration results in persistent epithelial and other defects on the ocular surface, termed diabetic keratopathy (DK), which progressively diminish vision and quality of life. Reports of delayed corneal wound healing and the reduced expression of putative stem cell markers in diabetic relative to healthy eyes suggest that the pathogenesis of DK may be associated with the abnormal activity of LESCs. However, the precise role of these cells in diabetic corneal disease is poorly understood and yet to be comprehensively explored. Herein, we review existing literature highlighting aberrant LESC activity in diabetes, focusing on factors that influence their form and function, and emerging therapies to correct these defects. The consequences of malfunctioning or depleted LESC stocks in DK and limbal stem cell deficiency (LSCD) are also discussed. These insights could be exploited to identify novel targets for improving the management of ocular surface complications that manifest in patients with diabetes.
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Affiliation(s)
| | - Nick Di Girolamo
- School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia;
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19
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Ghorbani S, Christine Füchtbauer A, Møllebjerg A, Møller Martensen P, Hvidbjerg Laursen S, Christian Evar Kraft D, Kjems J, Meyer RL, Rahimi K, Foss M, Füchtbauer EM, Sutherland DS. Protein ligand and nanotopography separately drive the phenotype of mouse embryonic stem cells. Biomaterials 2023; 301:122244. [PMID: 37459700 DOI: 10.1016/j.biomaterials.2023.122244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 07/09/2023] [Accepted: 07/12/2023] [Indexed: 09/06/2023]
Abstract
Biochemical and biomechanical signals regulate stem cell function in the niche environments in vivo. Current in vitro culture of mouse embryonic stem cells (mESC) uses laminin (LN-511) to provide mimetic biochemical signaling (LN-521 for human systems) to maintain stemness. Alternative approaches propose topographical cues to provide biomechanical cues, however combined biochemical and topographic cues may better mimic the in vivo environment, but are largely unexplored for in vitro stem cell expansion. In this study, we directly compare in vitro signals from LN-511 and/or topographic cues to maintain stemness, using systematically-varied submicron pillar patterns or flat surfaces with or without preadsorbed LN-511. The adhesion of cells, colony formation, expression of the pluripotency marker,octamer-binding transcription factor 4 (Oct4), and transcriptome profiling were characterized. We observed that either biochemical or topographic signals could maintain stemness of mESCs in feeder-free conditions, indicated by high-level Oct4 and gene profiling by RNAseq. The combination of LN-511 with nanotopography reduced colony growth, while maintaining stemness markers, shifted the cellular phenotype indicating that the integration of biochemical and topographic signals is antagonistic. Overall, significantly faster (up to 2.5 times) colony growth was observed at nanotopographies without LN-511, suggesting for improved ESC expansion.
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Affiliation(s)
- Sadegh Ghorbani
- Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus C, 8000, Denmark; The Centre for Cellular Signal Patterns (CELLPAT), Gustav Wieds Vej 14, Aarhus C, 8000, Denmark; Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
| | | | - Andreas Møllebjerg
- Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus C, 8000, Denmark
| | | | - Sara Hvidbjerg Laursen
- Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus C, 8000, Denmark
| | - David Christian Evar Kraft
- Department of Dentistry and Oral Health, Faculty of Health, University of Aarhus, Aarhus C, 8000, Denmark
| | - Jørgen Kjems
- Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus C, 8000, Denmark; The Centre for Cellular Signal Patterns (CELLPAT), Gustav Wieds Vej 14, Aarhus C, 8000, Denmark; Department of Molecular Biology, University of Aarhus, Aarhus C, 8000, Denmark
| | - Rikke Louise Meyer
- Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus C, 8000, Denmark
| | - Karim Rahimi
- Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus C, 8000, Denmark; Department of Molecular Biology, University of Aarhus, Aarhus C, 8000, Denmark
| | - Morten Foss
- Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus C, 8000, Denmark
| | | | - Duncan S Sutherland
- Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, Aarhus C, 8000, Denmark; The Centre for Cellular Signal Patterns (CELLPAT), Gustav Wieds Vej 14, Aarhus C, 8000, Denmark.
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20
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Melamed D, Choi A, Reilein A, Tavaré S, Kalderon D. Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions. PLoS Genet 2023; 19:e1010965. [PMID: 37747936 PMCID: PMC10553835 DOI: 10.1371/journal.pgen.1010965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 10/05/2023] [Accepted: 09/11/2023] [Indexed: 09/27/2023] Open
Abstract
Drosophila ovarian Follicle Stem Cells (FSCs) present a favorable paradigm for understanding how stem cell division and differentiation are balanced in communities where those activities are independent. FSCs also allow exploration of how this balance is integrated with spatial stem cell heterogeneity. Posterior FSCs become proliferative Follicle Cells (FCs), while anterior FSCs become quiescent Escort Cells (ECs) at about one fourth the frequency. A single stem cell can nevertheless produce both FCs and ECs because it can move between anterior and posterior locations. Studies based on EdU incorporation to approximate division rates suggested that posterior FSCs divide faster than anterior FSCs. However, direct measures of cell cycle times are required to ascertain whether FC output requires a net flow of FSCs from anterior to posterior. Here, by using live imaging and FUCCI cell-cycle reporters, we measured absolute division rates. We found that posterior FSCs cycle more than three times faster than anterior FSCs and produced sufficient new cells to match FC production. H2B-RFP dilution studies supported different cycling rates according to A/P location and facilitated live imaging, showing A/P exchange of FSCs in both directions, consistent with the dynamic equilibrium inferred from division rate measurements. Inversely graded Wnt and JAK-STAT pathway signals regulate FSC differentiation to ECs and FCs. JAK-STAT promotes both differentiation to FCs and FSC cycling, affording some coordination of these activities. When JAK-STAT signaling was manipulated to be spatially uniform, the ratio of posterior to anterior division rates was reduced but remained substantial, showing that graded JAK-STAT signaling only partly explains the graded cycling of FSCs. By using FUCCI markers, we found a prominent G2/M cycling restriction of posterior FSCs together with an A/P graded G1/S restriction, that JAK-STAT signaling promotes both G1/S and G2/M transitions, and that PI3 kinase signaling principally stimulates the G2/M transition.
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Affiliation(s)
- David Melamed
- Department of Biological Sciences, Columbia University, New York, New York State, United States of America
| | - Aaron Choi
- Department of Biological Sciences, Columbia University, New York, New York State, United States of America
| | - Amy Reilein
- Department of Biological Sciences, Columbia University, New York, New York State, United States of America
| | - Simon Tavaré
- Department of Biological Sciences, Columbia University, New York, New York State, United States of America
- Irving Institute for Cancer Dynamics & Department of Statistics, Columbia University, New York, New York State, United States of America
| | - Daniel Kalderon
- Department of Biological Sciences, Columbia University, New York, New York State, United States of America
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21
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Cheng C, Zhang S, Gong Y, Wang X, Tang S, Wan J, Ding K, Yuan C, Sun W, Yao LH. Cordycepin inhibits myogenesis via activating the ERK1/2 MAPK signalling pathway in C2C12 cells. Biomed Pharmacother 2023; 165:115163. [PMID: 37453196 DOI: 10.1016/j.biopha.2023.115163] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/02/2023] [Accepted: 07/11/2023] [Indexed: 07/18/2023] Open
Abstract
Cordycepin (with a molecular formula of C10H13N5O3), a natural adenosine isolated from Cordyceps militaris, has an important regulatory effect on skeletal muscle remodelling and quality maintenance. The aim of this study was to investigate the effect of cordycepin on myoblast differentiation and explore the underlying molecular mechanisms of this effect. Our results showed that cordycepin inhibited myogenesis by downregulating myogenic differentiation (MyoD) and myogenin (MyoG), preserved undifferentiated reserve cell pools by upregulating myogenic factor 5 (Myf5) and retinoblastoma-like protein p130 (p130), and enhanced energy reserves by decreasing intracellular reactive oxygen species (ROS) and enhancing mitochondrial membrane potential, mitochondrial mass, and ATP content. The effect of cordycepin on myogenesis was associated with increased phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2). PD98059 (a specific inhibitor of p-ERK1/2) attenuated the inhibitory effect of cordycepin on C2C12 differentiation. The present study reveals that cordycepin inhibits myogenesis through ERK1/2 MAPK signalling activation accompanied by an increase in skeletal muscle energy reserves and improving skeletal muscle oxidative stress, which may have implications for its further application for the prevention and treatment of degenerative muscle diseases caused by the depletion of depleted muscle stem cells.
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Affiliation(s)
- Chunfang Cheng
- School of Sport Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China
| | - Shasha Zhang
- School of Sport Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China
| | - Yanchun Gong
- School of Sport Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China; School of Life Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China
| | - Xuanyu Wang
- School of Sport Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China
| | - Shan Tang
- School of Sport Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China
| | - Juan Wan
- School of Sport Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China
| | - Kaizhi Ding
- School of Life Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China
| | - Chunhua Yuan
- School of Life Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China
| | - Wei Sun
- School of Life Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China
| | - Li-Hua Yao
- School of Sport Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China; School of Life Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China.
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22
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Jin C, Wang Z, Li P, Tang J, Jiao T, Li Y, Ou J, Zou D, Li M, Mang X, Liu J, Ma Y, Wu X, Shi J, Chen S, He M, Lu Y, Zhang N, Miao S, Sun F, Wang L, Li K, Yu J, Song W. Decoding the spermatogonial stem cell niche under physiological and recovery conditions in adult mice and humans. SCIENCE ADVANCES 2023; 9:eabq3173. [PMID: 37540753 PMCID: PMC10403211 DOI: 10.1126/sciadv.abq3173] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 07/03/2023] [Indexed: 08/06/2023]
Abstract
The intricate interaction between spermatogonial stem cell (SSC) and testicular niche is essential for maintaining SSC homeostasis; however, this interaction remains largely uncharacterized. In this study, to characterize the underlying signaling pathways and related paracrine factors, we delineated the intercellular interactions between SSC and niche cell in both adult mice and humans under physiological conditions and dissected the niche-derived regulation of SSC maintenance under recovery conditions, thus uncovering the essential role of C-C motif chemokine ligand 24 and insulin-like growth factor binding protein 7 in SSC maintenance. We also established the clinical relevance of specific paracrine factors in human fertility. Collectively, our work on decoding the adult SSC niche serves as a valuable reference for future studies on the aetiology, diagnosis, and treatment of male infertility.
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Affiliation(s)
- Cheng Jin
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
- Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan 528000, China
- Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhipeng Wang
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Pengyu Li
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Jielin Tang
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Tao Jiao
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Yiran Li
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Jinhuan Ou
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Dingfeng Zou
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Mengzhen Li
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Xinyu Mang
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Jun Liu
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Yanni Ma
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
- Center for Stem Cell and Regeneration Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College (PUMC), Chengdu 610052, China
| | - Xiaolong Wu
- Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226001, China
| | - Jie Shi
- Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226001, China
| | - Shitao Chen
- International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, China
| | - Manman He
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Yan Lu
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Ning Zhang
- Center for Stem Cell and Regeneration Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College (PUMC), Chengdu 610052, China
- Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU), School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
| | - Shiying Miao
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Fei Sun
- Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong 226001, China
| | - Linfang Wang
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Kai Li
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Jia Yu
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
- Center for Stem Cell and Regeneration Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College (PUMC), Chengdu 610052, China
| | - Wei Song
- Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
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23
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Szabó L, Seubert AC, Kretzschmar K. Modelling adult stem cells and their niche in health and disease with epithelial organoids. Semin Cell Dev Biol 2023; 144:20-30. [PMID: 36127261 DOI: 10.1016/j.semcdb.2022.09.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 09/06/2022] [Accepted: 09/08/2022] [Indexed: 10/14/2022]
Abstract
Adult stem cells are responsible for homoeostasis and regeneration of epithelial tissues. Stem cell function is regulated by both cell autonomous mechanisms as well as the niche. Deregulated stem cell function contributes to diseases such as cancer. Epithelial organoid cultures generated from tissue-resident adult stem cells have allowed unprecedented insights into the biology of epithelial tissues. The subsequent adaptation of organoid technology enabled the modelling of the communication of stem cells with their cellular and non-cellular niche as well as diseases. Starting from its first model described in 2009, the murine small intestinal organoid, we discuss here how epithelial organoid cultures have been become a prime in vitro research tool for cell and developmental biology, bioengineering, and biomedicine in the last decade.
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Affiliation(s)
- Lili Szabó
- Mildred Scheel Early Career Centre (MSNZ) for Cancer Research, University Hospital Würzburg, IZKF/MSNZ, Würzburg, Germany
| | - Anna C Seubert
- Mildred Scheel Early Career Centre (MSNZ) for Cancer Research, University Hospital Würzburg, IZKF/MSNZ, Würzburg, Germany
| | - Kai Kretzschmar
- Mildred Scheel Early Career Centre (MSNZ) for Cancer Research, University Hospital Würzburg, IZKF/MSNZ, Würzburg, Germany.
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24
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Kidwai FK, Canalis E, Robey PG. Induced pluripotent stem cell technology in bone biology. Bone 2023; 172:116760. [PMID: 37028583 PMCID: PMC10228209 DOI: 10.1016/j.bone.2023.116760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 03/31/2023] [Accepted: 04/04/2023] [Indexed: 04/09/2023]
Abstract
Technologies on the development and differentiation of human induced pluripotent stem cells (hiPSCs) are rapidly improving, and have been applied to create cell types relevant to the bone field. Differentiation protocols to form bona fide bone-forming cells from iPSCs are available, and can be used to probe details of differentiation and function in depth. When applied to iPSCs bearing disease-causing mutations, the pathogenetic mechanisms of diseases of the skeleton can be elucidated, along with the development of novel therapeutics. These cells can also be used for development of cell therapies for cell and tissue replacement.
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Affiliation(s)
- Fahad K Kidwai
- Skeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States of America
| | - Ernesto Canalis
- Center for Skeletal Research, Orthopedic Surgery and Medicine, UConn Musculoskeletal Institute, UConn Health, Farmington, CT 06030-4037, United States of America
| | - Pamela G Robey
- Skeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States of America.
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25
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Koka P, Chandramohan Y, Perumal E, Kavarthapu A, Dhanasekaran A, Chandran A, Gunasekaran K. Fabrication of ECM Mimicking Bioactive Scaffold: A Regenerative Approach for MSC Mediated Applications. Stem Cells Int 2023; 2023:6282987. [PMID: 37251796 PMCID: PMC10224790 DOI: 10.1155/2023/6282987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 03/19/2023] [Accepted: 04/27/2023] [Indexed: 05/31/2023] Open
Abstract
Biomaterials are feasible resources that aids to replace damaged structures in our bodies. The most biologically active flora is Aloe vera which has many bioactive compounds that are anti-inflammatory, antimicrobial, and have ECM mimicking protein content which helps in the healing of wounds and also acts as an ECM factor for stem cell homing and differentiation. The Aloe vera containing 10 w/v of gelatin was lyophilized. Scaffolds had sharper morphology, greater hydrophilic properties, and a Young's modulus of 6.28 MPa and 15.9 MPa of higher tensile strength are desirable. In tissue engineering and regenerative medicine, biologically active scaffolds have been producing hopeful outcomes in both restoration and replacement, respectively. The objective of the present investigation is to test the idea that incorporating gelatin to Aloe vera scaffolds might enhance their structure, good biocompatibility, and possibly even bioactivity. The SEM picture of the composite scaffold revealed pore walls. The scaffolds had linked pores with diameters ranging from 93 to 296 μm. Aloe vera and the matrix interact well, according to the FTIR study, which could lead to a reduction in the amount of water-binding sites and a reduction in the material's ability to absorb water. Aloe vera with 10% gelatin (AV/G) scaffold was investigated for different biological reactions of human gingival tissue mesenchymal stem cells (MSCs) in terms of cell proliferation, morphology, and cell migration. The results demonstrated the potential of the AV/G scaffold as a biomaterial that offers new insight in the field of tissue engineering.
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Affiliation(s)
- Pavani Koka
- Centre for Biotechnology, Anna University, Chennai, 600 025 Tamil Nadu, India
- Bioscreen Instrumentation Pvt Ltd, Ashok Nagar, Chennai, Tamil Nadu, India
| | - Yamini Chandramohan
- Centre for Biotechnology, Anna University, Chennai, 600 025 Tamil Nadu, India
| | - Elumalai Perumal
- Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - Avinash Kavarthapu
- Department of Periodontology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - Anuradha Dhanasekaran
- Cancer and Stem Cell Biology Laboratory, Centre for Biotechnology, Anna University, Chennai, 600 025 Tamil Nadu, India
| | - Anusha Chandran
- Department of Biotechnology, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India
| | - Krishnamoorthy Gunasekaran
- Department of Medical Biochemistry, College of Health Sciences, Dambi Dollo University, P.O. Box 360, Kelam Welega Zone, Oromia Region, Ethiopia
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26
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Koptyug A, Sukhovei Y, Kostolomova E, Unger I, Kozlov V. Novel Strategy in Searching for Natural Compounds with Anti-Aging and Rejuvenating Potential. Int J Mol Sci 2023; 24:ijms24098020. [PMID: 37175723 PMCID: PMC10178965 DOI: 10.3390/ijms24098020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 04/18/2023] [Accepted: 04/25/2023] [Indexed: 05/15/2023] Open
Abstract
We suggest a novel approach for searching natural compounds with anti-aging and rejuvenation potential using cell cultures, with a high potential for the further in vivo applications. The present paper discusses ways of defining age for cell populations with large numbers of cells and suggests a method of assessing how young or old a cell population is based on a cell age profile approach. This approach uses experimental distributions of the cells over the cell cycle stages, acquired using flow cytometry. This paper discusses how such a profile should evolve under homeostatic maintenance of cell numbers in the proliferation niches. We describe promising results from experiments on a commercial substance claiming rejuvenating and anti-aging activity acting upon the cultures of human mononuclear cells and dermal fibroblasts. The chosen substance promotes a shift towards larger proportion of cells in synthesis and proliferation stages, and increases cell culture longevity. Further, we describe promising in vivo testing results of a selected food supplement. Based on the described concept of cell age profile and available test results, a strategy to search for natural compounds with regenerative, anti-aging and rejuvenation potential is suggested and proposed for wider and thorough testing. Proposed methodology of age assessment is rather generic and can be used for quantitative assessment of the anti-aging and rejuvenation potential of different interventions. Further research aimed at the tests of the suggested strategy using more substances and different interventions, and the thorough studies of molecular mechanisms related to the action of the substance used for testing the suggested search methodology, are needed.
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Affiliation(s)
- Andrey Koptyug
- SportsTech Research Center, Department of Engineering, Mathematics and Science Education, Mid Sweden University, Akademigatan 1, 831 25 Östersund, Sweden
| | - Yurij Sukhovei
- Institute of Fundamental and Clinical Immunology, Tyumen Branch, Kotovskogo Str. 5, 625027 Tyumen, Russia
| | - Elena Kostolomova
- Department of Microbiology, Tyumen State Medical University, Kotovskogo Str. 5/2, 625023 Tyumen, Russia
| | - Irina Unger
- Institute of Fundamental and Clinical Immunology, Tyumen Branch, Kotovskogo Str. 5, 625027 Tyumen, Russia
| | - Vladimir Kozlov
- Institute of Fundamental and Clinical Immunology, Department of Clinical Immunology, Yadrintcevskaya Str. 14, 630099 Novosibirsk, Russia
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27
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Banjac I, Maimets M, Jensen KB. Maintenance of high-turnover tissues during and beyond homeostasis. Cell Stem Cell 2023; 30:348-361. [PMID: 37028402 DOI: 10.1016/j.stem.2023.03.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/23/2023] [Accepted: 03/15/2023] [Indexed: 04/09/2023]
Abstract
Tissues with a high turnover rate produce millions of cells daily and have abundant regenerative capacity. At the core of their maintenance are populations of stem cells that balance self-renewal and differentiation to produce the adequate numbers of specialized cells required for carrying out essential tissue functions. Here, we compare and contrast the intricate mechanisms and elements of homeostasis and injury-driven regeneration in the epidermis, hematopoietic system, and intestinal epithelium-the fastest renewing tissues in mammals. We highlight the functional relevance of the main mechanisms and identify open questions in the field of tissue maintenance.
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Affiliation(s)
- Isidora Banjac
- The Novo Nordisk Foundation Center for Stem Cell Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
| | - Martti Maimets
- The Novo Nordisk Foundation Center for Stem Cell Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
| | - Kim B Jensen
- The Novo Nordisk Foundation Center for Stem Cell Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
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28
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Lim SBH, Wei S, Tan AHM, van Steensel MAM, Lim X. Lrig1-expressing epidermal progenitors require SCD1 to maintain the dermal papilla niche. Sci Rep 2023; 13:4027. [PMID: 36899019 PMCID: PMC10006094 DOI: 10.1038/s41598-023-30411-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 02/22/2023] [Indexed: 03/12/2023] Open
Abstract
Niche cells are widely known to regulate stem/progenitor cells in many mammalian tissues. In the hair, dermal papilla niche cells are well accepted to regulate hair stem/progenitor cells. However, how niche cells themselves are maintained is largely unknown. We present evidence implicating hair matrix progenitors and the lipid modifying enzyme, Stearoyl CoA Desaturase 1, in the regulation of the dermal papilla niche during the anagen-catagen transition of the mouse hair cycle. Our data suggest that this takes place via autocrine Wnt signalling and paracrine Hedgehog signalling. To our knowledge, this is the first report demonstrating a potential role for matrix progenitor cells in maintaining the dermal papilla niche.
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Affiliation(s)
- Sophia Beng Hui Lim
- Institute of Medical Biology (IMB) / Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A*STAR), 11 Mandalay Road, Clinical Sciences Building #17-01, Singapore, 308232, Republic of Singapore
- NUS Graduate School, National University of Singapore, Singapore, 119077, Republic of Singapore
| | - Shang Wei
- Institute of Medical Biology (IMB) / Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A*STAR), 11 Mandalay Road, Clinical Sciences Building #17-01, Singapore, 308232, Republic of Singapore
| | - Andy Hee-Meng Tan
- Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, Centros, Singapore, 138668, Republic of Singapore
| | - Maurice A M van Steensel
- Institute of Medical Biology (IMB) / Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A*STAR), 11 Mandalay Road, Clinical Sciences Building #17-01, Singapore, 308232, Republic of Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore, 308232, Republic of Singapore
| | - Xinhong Lim
- Institute of Medical Biology (IMB) / Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A*STAR), 11 Mandalay Road, Clinical Sciences Building #17-01, Singapore, 308232, Republic of Singapore.
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29
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Alves ED, Benevenuto LGD, Morais BP, Barros MA, Achcar JA, Montrezor LH. Ovarian Microenvironment Modulation by Adipose-Mesenchymal Stem Cells and Photobiomodulation Can Alter Osteoblasts Functions In Vitro. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2023. [DOI: 10.1007/s40883-023-00297-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
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30
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Takashima Y, Matsumoto T, Nakano N, Kamenaga T, Kuroda Y, Hayashi S, Matsushita T, Niikura T, Kuroda R. The influence of ruptured scar pattern of human anterior cruciate ligament remnant tissue on tendon-bone healing in vivo. J Orthop Res 2023; 41:500-510. [PMID: 35634871 DOI: 10.1002/jor.25387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 04/12/2022] [Accepted: 05/26/2022] [Indexed: 02/04/2023]
Abstract
The purpose of this study was to determine whether the transplantation of human cells from a non-reattached injured anterior cruciate ligament (ACL) remnant could enhance tendon-bone healing. Human ACL remnant tissue was classified into two groups based on the morphologic pattern as per Crain's classification: (1) non-reattachment group (Crain Ⅳ) and (2) reattachment group (Crain Ⅰ-Ⅲ). Seventy-five 10-week-old immunodeficient rats underwent ACL reconstruction followed by intracapsular administration of one of the following: (1) ACL-derived cells from the non-reattached remnant (non-reattachment group) (n = 5), (2) ACL-derived cells from the reattached tissue (reattachment group) (n = 5), or (3) phosphate-buffered saline (PBS) only (PBS group) (n = 5). Histological (Weeks 2, 4, and 8), immunohistochemical (Week 2), radiographic (Weeks 0, 2, 4, and 8), and biomechanical (Week 8) assessments were performed. Histological evaluation showed high and early healing, induction of endochondral ossification-like integration, and mature bone ingrowth at Week 4 in the non-reattachment group. Microcomputed tomography at Week 4 showed that the tibial bone tunnels in the non-reattachment group were significantly reduced compared to those in the reattachment and PBS groups. Moreover, biomechanical testing showed that ultimate load-to-failure in the non-reattachment group tended to be larger than that in the reattachment group, though not statistically significant. The enhanced healing potential in the non-reattachment group was explained by the increase in intrinsic angiogenesis/osteogenesis. In the subacute phase, the ACL-derived cells with the non-reattached morphologic pattern showed greater and earlier tendon bone healing compared with the cells obtained from the reattached morphologic pattern.
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Affiliation(s)
- Yoshinori Takashima
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Naoki Nakano
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Kamenaga
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuichi Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shinya Hayashi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takehiko Matsushita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takahiro Niikura
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
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31
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Tu CC, Cheng NC, Yu J, Pan YX, Tai WC, Chen YC, Chang PC. Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects. Stem Cell Res Ther 2023; 14:20. [PMID: 36737813 PMCID: PMC9898981 DOI: 10.1186/s13287-023-03238-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 01/10/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Diabetes mellitus deteriorates the destruction and impairs the healing of periodontal wounds and craniofacial defects. This study is to evaluate the potential of self-assembled adipose-derived stem cell spheroids (ADsp) in microbial transglutaminase cross-linked gelatin hydrogel (mTG) for treating diabetic periodontal wounds and craniofacial defects. METHODS Human adipose-derived stem cells (ADSCs) were isolated by lipoaspiration, pluripotent genes and trilineage differentiation were examined, and the maintenance of ADsp properties in mTG was verified. Oral mucosal wounds and calvarial osseous defects were created in diabetic rats. Gross observation, histologic evaluation, and immunohistochemistry for proliferating cells and keratinization were conducted in the mucosal wounds within 4-28 days. Micro-CT imaging, histologic evaluation, and immunohistochemistry for proliferating cells and osteogenic differentiation were conducted in the osseous defects at 7 and 28 days. RESULTS ADSCs expressed pluripotent genes and were capable of trilineage differentiation. ADsp retained morphology and stemness in mTG. In diabetic mucosal wounds, wound closure, epithelization, and keratinization were accelerated in those with ADsp and ADsp-mTG. In diabetic osseous defects, osteogenic differentiation markers were evidently expressed, cell proliferation was promoted from day 7, and bone formation was significantly promoted at day 28 in those with osteogenically pretreated ADsp-mTG. CONCLUSIONS ADsp-mTG accelerated diabetic oral mucosal wound healing, and osteogenically pretreated ADsp-mTG promoted diabetic osseous defect regeneration, proving that ADsp-mTG facilitated diabetic periodontal wound healing and craniofacial osseous defect regeneration.
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Affiliation(s)
- Che-Chang Tu
- Graduate Institute of Clinical Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan
- Division of Periodontics, Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
| | - Nai-Chen Cheng
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Jiashing Yu
- Department of Chemical Engineering, College of Engineering, National Taiwan University, Taipei, Taiwan
| | - Yi-Xuan Pan
- Division of Periodontics, Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
- Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Wei-Chiu Tai
- Graduate Institute of Clinical Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yin-Chuan Chen
- Department of Chemical Engineering, College of Engineering, National Taiwan University, Taipei, Taiwan
| | - Po-Chun Chang
- Graduate Institute of Clinical Dentistry, School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
- Division of Periodontics, Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
- School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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32
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Barzegari A, Omidi Y, Gueguen V, Meddahi-Pellé A, Letourneur D, Pavon-Djavid G. Nesting and fate of transplanted stem cells in hypoxic/ischemic injured tissues: The role of HIF1α/sirtuins and downstream molecular interactions. Biofactors 2023; 49:6-20. [PMID: 32939878 DOI: 10.1002/biof.1674] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/29/2020] [Accepted: 07/31/2020] [Indexed: 12/15/2022]
Abstract
The nesting mechanisms and programming for the fate of implanted stem cells in the damaged tissue have been critical issues in designing and achieving cell therapies. The fracture site can induce senescence or apoptosis based on the surrounding harsh conditions, hypoxia, and oxidative stress (OS). Respiration deficiency, disruption in energy metabolism, and consequently OS induction change the biophysical, biochemical, and cellular components of the native tissue. Additionally, the homeostatic molecular players and cell signaling might be changed. Despite all aforementioned issues, in the native stem cell niche, physiological hypoxia is not toxic; rather, it is vitally required for homing, self-renewal, and differentiation. Hence, the key macromolecular players involved in the support of stem cell survival and re-adaptation to a new dysfunctional niche must be understood for managing the cell therapy outcome. Hypoxia-inducible factor 1-alpha is the master transcriptional regulator, involved in the cell response to hypoxia and the adaptation of stem cells to a new niche. This protein is regulated by interaction with sirtuins. Sirtuins are highly conserved NAD+-dependent enzymes that monitor the cellular energy status and modulate gene transcription, genome stability, and energy metabolism in response to environmental signals to modulate the homing and fate of stem cells. Herein, new insights into the nesting of stem cells in hypoxic-ischemic injured tissues were provided and their programming in a new dysfunctional niche along with the involved complex macromolecular players were critically discussed.
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Affiliation(s)
- Abolfazl Barzegari
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yadollah Omidi
- Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, Florida
| | - Virginie Gueguen
- INSERM U1148, Laboratory for Vascular Translational Science, Cardiovascular Bioengineering, Université Sorbonne Paris Nord, Villetaneuse, France
| | - Anne Meddahi-Pellé
- INSERM U1148, Laboratory for Vascular Translational Science, Cardiovascular Bioengineering, Université Sorbonne Paris Nord, Villetaneuse, France
| | - Didier Letourneur
- INSERM U1148, Laboratory for Vascular Translational Science, Cardiovascular Bioengineering, Université Sorbonne Paris Nord, Villetaneuse, France
| | - Graciela Pavon-Djavid
- INSERM U1148, Laboratory for Vascular Translational Science, Cardiovascular Bioengineering, Université Sorbonne Paris Nord, Villetaneuse, France
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Xu Y, Cai S, Wang Q, Cheng M, Hui X, Dzakah EE, Zhao B, Chen X. Multi-Lineage Human Endometrial Organoids on Acellular Amniotic Membrane for Endometrium Regeneration. Cell Transplant 2023; 32:9636897231218408. [PMID: 38097275 PMCID: PMC10725651 DOI: 10.1177/09636897231218408] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 11/18/2023] [Accepted: 11/18/2023] [Indexed: 12/18/2023] Open
Abstract
Asherman's syndrome is an endometrial regeneration disorder resulting from injury to the endometrial basal layer, causing the formation of scar tissue in the uterus and cervix. This usually leads to uterine infertility, menstrual disorders, and placental abnormalities. While stem cell therapy has shown extensive progress in repairing the damaged endometrium and preventing intrauterine adhesion, issues of low engraftment rates, rapid senescence, and the risk of tumorigenesis remain to be resolved for efficient and effective application of this technology in endometrial repair. This study addressed these challenges by developing a co-culture system to generate multi-lineage endometrial organoids (MLEOs) comprising endometrial epithelium organoids (EEOs) and endometrial mesenchymal stem cells (eMSCs). The efficacy of these MLEOs was investigated by seeding them on a biocompatible scaffold, the human acellular amniotic membrane (HAAM), to create a biological graft patch, which was subsequently transplanted into an injury model of the endometrium in rats. The results indicated that the MLEOs on the HAAM patch facilitated endometrial angiogenesis, regeneration, and improved pregnancy outcomes. The MLEOs on the HAAM patch could serve as a promising strategy for treating endometrial injury and preventing Asherman's syndrome.
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Affiliation(s)
- Yuhui Xu
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
| | - Shuyan Cai
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
| | - Qian Wang
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
| | - Minzhang Cheng
- School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
- Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xianrui Hui
- Institute of Organoid Technology, bioGenous Biotechnology, Inc., Suzhou, China
| | | | - Bing Zhao
- School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
- Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Institute of Organoid Technology, bioGenous Biotechnology, Inc., Suzhou, China
- Institute of Organoid Technology, Kunming Medical University, Kunming, China
| | - Xiaojun Chen
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
- Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
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Geevarghese R, Sajjadi SS, Hudecki A, Sajjadi S, Jalal NR, Madrakian T, Ahmadi M, Włodarczyk-Biegun MK, Ghavami S, Likus W, Siemianowicz K, Łos MJ. Biodegradable and Non-Biodegradable Biomaterials and Their Effect on Cell Differentiation. Int J Mol Sci 2022; 23:ijms232416185. [PMID: 36555829 PMCID: PMC9785373 DOI: 10.3390/ijms232416185] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 12/05/2022] [Accepted: 12/09/2022] [Indexed: 12/23/2022] Open
Abstract
Biomaterials for tissue scaffolds are key components in modern tissue engineering and regenerative medicine. Targeted reconstructive therapies require a proper choice of biomaterial and an adequate choice of cells to be seeded on it. The introduction of stem cells, and the transdifferentiation procedures, into regenerative medicine opened a new era and created new challenges for modern biomaterials. They must not only fulfill the mechanical functions of a scaffold for implanted cells and represent the expected mechanical strength of the artificial tissue, but furthermore, they should also assure their survival and, if possible, affect their desired way of differentiation. This paper aims to review how modern biomaterials, including synthetic (i.e., polylactic acid, polyurethane, polyvinyl alcohol, polyethylene terephthalate, ceramics) and natural (i.e., silk fibroin, decellularized scaffolds), both non-biodegradable and biodegradable, could influence (tissue) stem cells fate, regulate and direct their differentiation into desired target somatic cells.
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Affiliation(s)
- Rency Geevarghese
- Biotechnology Center, Silesian University of Technology, 44-100 Gliwice, Poland
| | - Seyedeh Sara Sajjadi
- School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1971653313, Iran
| | - Andrzej Hudecki
- Łukasiewicz Network-Institute of Non-Ferrous Metals, 44-121 Gliwice, Poland
| | - Samad Sajjadi
- School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1971653313, Iran
| | | | - Tayyebeh Madrakian
- Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6516738695, Iran
- Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran
| | - Mazaher Ahmadi
- Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6516738695, Iran
- Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran
| | - Małgorzata K. Włodarczyk-Biegun
- Biotechnology Center, Silesian University of Technology, 44-100 Gliwice, Poland
- Polymer Science, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
| | - Saeid Ghavami
- Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran
- Department of Human Anatomy and Cell Science, University of Manitoba College of Medicine, Winnipeg, MB R3E 0V9, Canada
- Research Institutes of Oncology and Hematology, Cancer Care Manitoba-University of Manitoba, Winnipeg, MB R3E 0V9, Canada
- Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada
- Faculty of Medicine in Zabrze, University of Technology in Katowice, 41-800 Zabrze, Poland
| | - Wirginia Likus
- Department of Anatomy, Faculty of Health Sciences in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
| | - Krzysztof Siemianowicz
- Department of Biochemistry, Faculty of Medicine in Katowice, Medical University of Silesia, 40-752 Katowice, Poland
- Correspondence: (K.S.); (M.J.Ł.); Tel.: +48-32-237-2913 (M.J.Ł.)
| | - Marek J. Łos
- Biotechnology Center, Silesian University of Technology, 44-100 Gliwice, Poland
- Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran
- Correspondence: (K.S.); (M.J.Ł.); Tel.: +48-32-237-2913 (M.J.Ł.)
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Bogov (jr.) AA, Akhtyamov IF, Danilov VI, Starostina IG, Khannanova IG, Bogov AA. Treatment of a damaged brachial plexus with help of stromal vascular fraction cell from adipose tissue. BULLETIN OF THE MEDICAL INSTITUTE "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH) 2022. [DOI: 10.20340/vmi-rvz.2023.1.clin.3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
The aim of the study – to accelerate the repair of the damaged brachial plexus using cells of the stromal vascular fraction isolated from adipose tissue.Materials and methods. The study was carried out in 62 patients using stromal-vascular fraction cells from adipose tissue and classical methods of treatment for brachial plexus injury. The effectiveness of regeneration was evaluated using electromyographic examination and positive recovery of motor and sensory function.Results and discussion. Assessment of the results of surgical treatment with stromal vascular fraction cells from adipose tissue after brachial plexus neurolysis revealed the restoration of early M3-M5 and S3-S4 functions in 90 % of patients, and in the comparison group – 68 % respectively. The number of patients with M4-M5 functions in the group using the stromal vascular fraction for brachial plexus neurotization was 85 %, while in the control group it was 64 %, respectively. Electroneuromyography data also indicated an increase in the average number of motor units by 30 % after using cells of the stromal-vascular fraction from adipose tissue, in contrast to the comparison group.Conclusion. Stromal vascular cells isolated from adipose tissue appear to be promising stimulants of brachial plexus injury repair.
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Affiliation(s)
- A. A. Bogov (jr.)
- Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
| | | | - V. I. Danilov
- Cazan State Medical University; Interregional Clinical Diagnostic Center
| | | | - I. G. Khannanova
- Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
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Willis TL, Lodge EJ, Andoniadou CL, Yianni V. Cellular interactions in the pituitary stem cell niche. Cell Mol Life Sci 2022; 79:612. [PMID: 36451046 PMCID: PMC9712314 DOI: 10.1007/s00018-022-04612-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 09/27/2022] [Accepted: 10/25/2022] [Indexed: 12/03/2022]
Abstract
Stem cells in the anterior pituitary gland can give rise to all resident endocrine cells and are integral components for the appropriate development and subsequent maintenance of the organ. Located in discreet niches within the gland, stem cells are involved in bi-directional signalling with their surrounding neighbours, interactions which underpin pituitary gland homeostasis and response to organ challenge or physiological demand. In this review we highlight core signalling pathways that steer pituitary progenitors towards specific endocrine fate decisions throughout development. We further elaborate on those which are conserved in the stem cell niche postnatally, including WNT, YAP/TAZ and Notch signalling. Furthermore, we have collated a directory of single cell RNA sequencing studies carried out on pituitaries across multiple organisms, which have the potential to provide a vast database to study stem cell niche components in an unbiased manner. Reviewing published data, we highlight that stem cells are one of the main signalling hubs within the anterior pituitary. In future, coupling single cell sequencing approaches with genetic manipulation tools in vivo, will enable elucidation of how previously understudied signalling pathways function within the anterior pituitary stem cell niche.
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Affiliation(s)
- Thea L Willis
- Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK
| | - Emily J Lodge
- Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK
| | - Cynthia L Andoniadou
- Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK.
- Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
| | - Val Yianni
- Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK.
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Siddall NA, Casagranda F, Johanson TM, Dominado N, Heaney J, Sutherland JM, McLaughlin EA, Hime GR. MiMIC analysis reveals an isoform specific role for Drosophila Musashi in follicle stem cell maintenance and escort cell function. Cell Death Dis 2022; 8:455. [DOI: 10.1038/s41420-022-01245-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 10/30/2022] [Accepted: 10/31/2022] [Indexed: 11/13/2022]
Abstract
AbstractThe Drosophila ovary is regenerated from germline and somatic stem cell populations that have provided fundamental conceptual understanding on how adult stem cells are regulated within their niches. Recent ovarian transcriptomic studies have failed to identify mRNAs that are specific to follicle stem cells (FSCs), suggesting that their fate may be regulated post-transcriptionally. We have identified that the RNA-binding protein, Musashi (Msi) is required for maintaining the stem cell state of FSCs. Loss of msi function results in stem cell loss, due to a change in differentiation state, indicated by upregulation of Lamin C in the stem cell population. In msi mutant ovaries, Lamin C upregulation was also observed in posterior escort cells that interact with newly formed germ cell cysts. Mutant somatic cells within this region were dysfunctional, as evidenced by the presence of germline cyst collisions, fused egg chambers and an increase in germ cell cyst apoptosis. The msi locus produces two classes of mRNAs (long and short). We show that FSC maintenance and escort cell function specifically requires the long transcripts, thus providing the first evidence of isoform-specific regulation in a population of Drosophila epithelial cells. We further demonstrate that although male germline stem cells have previously been shown to require Msi function to prevent differentiation this is not the case for female germline stem cells, indicating that these similar stem cell types have different requirements for Msi, in addition to the differential use of Msi isoforms between soma and germline. In summary, we show that different isoforms of the Msi RNA-binding protein are expressed in specific cell populations of the ovarian stem cell niche where Msi regulates stem cell differentiation, niche cell function and subsequent germ cell survival and differentiation.
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Altshuler A, Wickström SA, Shalom-Feuerstein R. Spotlighting adult stem cells: advances, pitfalls, and challenges. Trends Cell Biol 2022; 33:477-494. [PMID: 36270939 DOI: 10.1016/j.tcb.2022.09.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 09/09/2022] [Accepted: 09/16/2022] [Indexed: 11/06/2022]
Abstract
The existence of stem cells (SCs) at the tip of the cellular differentiation hierarchy has fascinated the scientific community ever since their discovery in the early 1950s to 1960s. Despite the remarkable success of the SC theory and the development of SC-based treatments, fundamental features of SCs remain enigmatic. Recent advances in single-cell lineage tracing, live imaging, and genomic technologies have allowed capture of life histories and transcriptional signatures of individual cells, leaving SCs much less space to 'hide'. Focusing on epithelial SCs and comparing them to other SCs, we discuss new paradigms of the SC niche, dynamics, and pathology, highlighting key open questions in SC biology that need to be resolved for harnessing SC potential in regenerative medicine.
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A reductionist approach to determine the effect of cell-cell contact on human epidermal stem cell differentiation. Acta Biomater 2022; 150:265-276. [PMID: 35926780 PMCID: PMC9810539 DOI: 10.1016/j.actbio.2022.07.054] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 07/23/2022] [Accepted: 07/27/2022] [Indexed: 01/07/2023]
Abstract
The balance between stem cell renewal and differentiation is determined by the interplay between intrinsic cellular controls and extrinsic factors presented by the microenvironment, or 'niche'. Previous studies on cultured human epidermis have utilised suspension culture and restricted cell spreading to investigate regulation of differentiation in single keratinocytes. However, keratinocytes are typically adherent to neighbouring cells in vivo. We therefore developed experimental models to investigate the combined effects of cell-ECM adhesion and cell-cell contact. We utilized lipid-modified oligonucleotides to form clusters of keratinocytes which were subsequently placed in suspension to induce terminal differentiation. In this experimental model cell-cell contact had no effect on suspension-induced differentiation of keratinocytes. We next developed a high-throughput platform for robust geometrical confinement of keratinocytes to hexagonal ECM-coated islands permitting direct cell-cell contact between single cells. As in the case of circular islands, differentiation was stimulated on the smallest single hexagonal islands. However, the percentage of involucrin-positive cells on small bowtie islands was significantly lower than on single islands, demonstrating that cell-cell contact reduced differentiation in response to decreased substrate adhesion. None of the small bowtie islands contained two involucrin-positive cells. Rather, if one cell was involucrin-positive the other was involucrin-negative. This suggests that there is intrinsic asymmetry in the effect of cell-cell contact in decreasing differentiation. Thus, our reductionist approaches provide new insights into the effect of the niche on keratinocyte differentiation. STATEMENT OF SIGNIFICANCE: Stem cell behaviour is regulated by a combination of external signals, including the nature of the adhesive substrate and cell-cell interactions. An understanding of how different signals are integrated creates the possibility of developing new biomaterials to promote tissue regeneration and broaden our understanding of skin diseases such as eczema and psoriasis, in which stem cell proliferation and differentiation are perturbed. In this study we have applied two methods to engineer intercellular adhesion of human epidermal stem cells, one involving lipid-modified DNA and the other involving hexagonal micropatterns. We show that the effect of cell-cell adhesion depends on cell-substrate adhesion and uncover evidence that two cells in equivalent environments can nevertheless behave differently.
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40
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Lim R, Banerjee A, Biswas R, Chari AN, Raghavan S. Mechanotransduction through adhesion molecules: Emerging roles in regulating the stem cell niche. Front Cell Dev Biol 2022; 10:966662. [PMID: 36172276 PMCID: PMC9511051 DOI: 10.3389/fcell.2022.966662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 07/18/2022] [Indexed: 11/23/2022] Open
Abstract
Stem cells have been shown to play an important role in regenerative medicine due to their proliferative and differentiation potential. The challenge, however, lies in regulating and controlling their potential for this purpose. Stem cells are regulated by growth factors as well as an array of biochemical and mechanical signals. While the role of biochemical signals and growth factors in regulating stem cell homeostasis is well explored, the role of mechanical signals has only just started to be investigated. Stem cells interact with their niche or to other stem cells via adhesion molecules that eventually transduce mechanical cues to maintain their homeostatic function. Here, we present a comprehensive review on our current understanding of the influence of the forces perceived by cell adhesion molecules on the regulation of stem cells. Additionally, we provide insights on how this deeper understanding of mechanobiology of stem cells has translated toward therapeutics.
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Affiliation(s)
- Ryan Lim
- A∗STAR Skin Research Lab (ASRL), Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove, Singapore, Singapore
| | - Avinanda Banerjee
- A∗STAR Skin Research Lab (ASRL), Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove, Singapore, Singapore
| | - Ritusree Biswas
- Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore, India
- Sastra University, Thanjavur, TN, India
| | - Anana Nandakumar Chari
- A∗STAR Skin Research Lab (ASRL), Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove, Singapore, Singapore
| | - Srikala Raghavan
- A∗STAR Skin Research Lab (ASRL), Agency for Science, Technology and Research (A*STAR) 8A Biomedical Grove, Singapore, Singapore
- Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore, India
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Yu WJ, Li N, Gong TT, Zhang JY, Jiang YT, Zhao YH, Huang YH, Li J, Liu S, Chen YL, Li LL, Jiang CZ, Chen ZJ, Wu QJ. Association Between Maternal Exposure to SO2 and Congenital Ear Malformations in Offspring: A Population-Based Case-Control Study in Liaoning Province, China. Int J Public Health 2022; 67:1604945. [PMID: 35872708 PMCID: PMC9302193 DOI: 10.3389/ijph.2022.1604945] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 06/09/2022] [Indexed: 11/13/2022] Open
Abstract
Objectives: To examine associations between maternal sulfur dioxide (SO2) exposure and congenital ear malformations risk in offspring.Methods: We surveyed 1676 cases with congenital ear malformations and 7950 controls from the Maternal and Child Health Certificate Registry of Liaoning Province between 2010 and 2015. SO2 concentrations were obtained from the Municipal Environment Protection Bureau of Liaoning Province. Multivariable logistic regression models and Restricted cubic splines (RCS) model were used to assess the aforementioned association.Results: There were significant associations between maternal SO2 exposure and congenital ear malformations risk during the 3 months before conception (OR Q4 vs. Q1 = 1.93, 95% CI = 1.43–2.59) and the 3 months after conception (OR Q4 vs. Q1 = 1.63, 95% CI = 1.22–2.18). Similar results were obtained in the analysis of single-month exposure windows, except for the third month before conception and the third month after conception. Moreover, these findings were broadly consistent across subgroups and robust in sensitivity analyses. There were non-linear dose-response associations between SO2 exposure and congenital ear malformations based on restricted cubic spline model analysis.Conclusion: Maternal SO2 exposure is associated with increased congenital ear malformations risk in offspring.
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Affiliation(s)
- Wei-Jun Yu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Institute for Prevention and Control of Infection and Infectious Diseases, Liaoning Provincial Center for Disease Control and Prevention, Shenyang, China
| | - Na Li
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ting-Ting Gong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Ting-Ting Gong, ; Qi-Jun Wu,
| | - Jia-Yu Zhang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu-Ting Jiang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu-Hong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yan-Hong Huang
- Department of Ophthalmology, Shenyang Women’s and Children’s Hospital, Shenyang, China
| | - Jing Li
- Department of Science and Education, Shenyang Maternity and Child Health Hospital, Shenyang, China
| | - Shu Liu
- Department of Atmospheric Environment Monitoring, Liaoning Eco-environmental Monitoring Center, Shenyang, China
| | - Yan-Ling Chen
- Office of Institution, Liaoning Women and Children’s Health Hospital, Shenyang, China
| | - Li-Li Li
- Department of Children’s Health Prevention, Shenyang Maternity and Child Health Hospital, Shenyang, China
| | - Cheng-Zhi Jiang
- School of Environmental and Chemical Engineering, Shenyang Ligong University, Shenyang, China
| | - Zong-Jiao Chen
- Department of Atmospheric Environment Monitoring, Liaoning Eco-environmental Monitoring Center, Shenyang, China
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Ting-Ting Gong, ; Qi-Jun Wu,
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42
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Sipilä K, Rognoni E, Jokinen J, Tewary M, Vietri Rudan M, Talvi S, Jokinen V, Dahlström KM, Liakath-Ali K, Mobasseri A, Du-Harpur X, Käpylä J, Nutt SL, Salminen TA, Heino J, Watt FM. Embigin is a fibronectin receptor that affects sebaceous gland differentiation and metabolism. Dev Cell 2022; 57:1453-1465.e7. [PMID: 35671757 PMCID: PMC9616737 DOI: 10.1016/j.devcel.2022.05.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 03/19/2022] [Accepted: 05/16/2022] [Indexed: 12/25/2022]
Abstract
Stem cell renewal and differentiation are regulated by interactions with the niche. Although multiple cell populations have been identified in distinct anatomical compartments, little is known about niche-specific molecular factors. Using skin as a model system and combining single-cell RNA-seq data analysis, immunofluorescence, and transgenic mouse models, we show that the transmembrane protein embigin is specifically expressed in the sebaceous gland and that the number of embigin-expressing cells is negatively regulated by Wnt. The loss of embigin promotes exit from the progenitor compartment and progression toward differentiation, and also compromises lipid metabolism. Embigin modulates sebaceous niche architecture by affecting extracellular matrix organization and basolateral targeting of monocarboxylate transport. We discover through ligand screening that embigin is a direct fibronectin receptor, binding to the N-terminal fibronectin domain without impairing integrin function. Our results solve the long-standing question of how embigin regulates cell adhesion and demonstrate a mechanism that couples adhesion and metabolism.
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Affiliation(s)
- Kalle Sipilä
- Centre for Gene Therapy & Regenerative Medicine, King's College London, London SE1 9RT, UK
| | - Emanuel Rognoni
- Centre for Cell Biology and Cutaneous Research, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
| | - Johanna Jokinen
- Department of Life Technologies, University of Turku, Turku 20014, Finland
| | - Mukul Tewary
- Centre for Gene Therapy & Regenerative Medicine, King's College London, London SE1 9RT, UK
| | - Matteo Vietri Rudan
- Centre for Gene Therapy & Regenerative Medicine, King's College London, London SE1 9RT, UK
| | - Salli Talvi
- Department of Life Technologies, University of Turku, Turku 20014, Finland
| | - Ville Jokinen
- Department of Life Technologies, University of Turku, Turku 20014, Finland
| | - Käthe M Dahlström
- Structural Bioinformatics Laboratory, InFLAMES Research Flagship Center, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland
| | - Kif Liakath-Ali
- Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA
| | - Atefeh Mobasseri
- Centre for Gene Therapy & Regenerative Medicine, King's College London, London SE1 9RT, UK
| | - Xinyi Du-Harpur
- Centre for Gene Therapy & Regenerative Medicine, King's College London, London SE1 9RT, UK; The Francis Crick Institute, London NW1 1AT, UK
| | - Jarmo Käpylä
- Department of Life Technologies, University of Turku, Turku 20014, Finland
| | - Stephen L Nutt
- The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia
| | - Tiina A Salminen
- Structural Bioinformatics Laboratory, InFLAMES Research Flagship Center, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland
| | - Jyrki Heino
- Department of Life Technologies, University of Turku, Turku 20014, Finland
| | - Fiona M Watt
- Centre for Gene Therapy & Regenerative Medicine, King's College London, London SE1 9RT, UK; European Molecular Biology Laboratory, Heidelberg 69117, Germany.
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Zhou J, Nie Y, Jin C, Zhang JXJ. Engineering Biomimetic Extracellular Matrix with Silica Nanofibers: From 1D Material to 3D Network. ACS Biomater Sci Eng 2022; 8:2258-2280. [PMID: 35377596 DOI: 10.1021/acsbiomaterials.1c01525] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Biomaterials at nanoscale is a fast-expanding research field with which extensive studies have been conducted on understanding the interactions between cells and their surrounding microenvironments as well as intracellular communications. Among many kinds of nanoscale biomaterials, mesoporous fibrous structures are especially attractive as a promising approach to mimic the natural extracellular matrix (ECM) for cell and tissue research. Silica is a well-studied biocompatible, natural inorganic material that can be synthesized as morpho-genetically active scaffolds by various methods. This review compares silica nanofibers (SNFs) to other ECM materials such as hydrogel, polymers, and decellularized natural ECM, summarizes fabrication techniques for SNFs, and discusses different strategies of constructing ECM using SNFs. In addition, the latest progress on SNFs synthesis and biomimetic ECM substrates fabrication is summarized and highlighted. Lastly, we look at the wide use of SNF-based ECM scaffolds in biological applications, including stem cell regulation, tissue engineering, drug release, and environmental applications.
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Affiliation(s)
- Junhu Zhou
- Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755, United States
| | - Yuan Nie
- Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755, United States
| | - Congran Jin
- Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755, United States
| | - John X J Zhang
- Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755, United States
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Khorasani N, Sadeghi M. A computational model of stem cells' decision-making mechanism to maintain tissue homeostasis and organization in the presence of stochasticity. Sci Rep 2022; 12:9167. [PMID: 35654903 PMCID: PMC9163052 DOI: 10.1038/s41598-022-12717-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 05/10/2022] [Indexed: 11/09/2022] Open
Abstract
The maintenance of multi-cellular developed tissue depends on the proper cell production rate to replace the cells destroyed by the programmed process of cell death. The stem cell is the main source of producing cells in a developed normal tissue. It makes the stem cell the lead role in the scene of a fully formed developed tissue to fulfill its proper functionality. By focusing on the impact of stochasticity, here, we propose a computational model to reveal the internal mechanism of a stem cell, which generates the right proportion of different types of specialized cells, distribute them into their right position, and in the presence of intercellular reactions, maintain the organized structure in a homeostatic state. The result demonstrates that the spatial pattern could be harassed by the population geometries. Besides, it clearly shows that our model with progenitor cells able to recover the stem cell presence could retrieve the initial pattern appropriately in the case of injury. One of the fascinating outcomes of this project is demonstrating the contradictory roles of stochasticity. It breaks the proper boundaries of the initial spatial pattern in the population. While, on the flip side of the coin, it is the exact factor that provides the demanded non-genetic diversity in the tissue. The remarkable characteristic of the introduced model as the stem cells' internal mechanism is that it could control the overall behavior of the population without need for any external factors.
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Affiliation(s)
- Najme Khorasani
- School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.
| | - Mehdi Sadeghi
- National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
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Barbiera A, Sorrentino S, Fard D, Lepore E, Sica G, Dobrowolny G, Tamagnone L, Scicchitano BM. Taurine Administration Counteracts Aging-Associated Impingement of Skeletal Muscle Regeneration by Reducing Inflammation and Oxidative Stress. Antioxidants (Basel) 2022; 11:antiox11051016. [PMID: 35624880 PMCID: PMC9137670 DOI: 10.3390/antiox11051016] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/17/2022] [Accepted: 05/18/2022] [Indexed: 02/05/2023] Open
Abstract
Sarcopenia, which occurs during aging, is characterized by the gradual loss of skeletal muscle mass and function, resulting in a functional decline in physical abilities. Several factors contribute to the onset of sarcopenia, including reduced regenerative capacity, chronic low-grade inflammation, mitochondrial dysfunction, and increased oxidative stress, leading to the activation of catabolic pathways. Physical activity and adequate protein intake are considered effective strategies able to reduce the incidence and severity of sarcopenia by exerting beneficial effects in improving the muscular anabolic response during aging. Taurine is a non-essential amino acid that is highly expressed in mammalian tissues and, particularly, in skeletal muscle where it is involved in the regulation of biological processes and where it acts as an antioxidant and anti-inflammatory factor. Here, we evaluated whether taurine administration in old mice counteracts the physiopathological effects of aging in skeletal muscle. We showed that, in injured muscle, taurine enhances the regenerative process by downregulating the inflammatory response and preserving muscle fiber integrity. Moreover, taurine attenuates ROS production in aged muscles by maintaining a proper cellular redox balance, acting as an antioxidant molecule. Although further studies are needed to better elucidate the molecular mechanisms responsible for the beneficial effect of taurine on skeletal muscle homeostasis, these data demonstrate that taurine administration ameliorates the microenvironment allowing an efficient regenerative process and attenuation of the catabolic pathways related to the onset of sarcopenia.
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Affiliation(s)
- Alessandra Barbiera
- Sezione di Istologia ed Embriologia, Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Roma, Italy; (A.B.); (S.S.); (D.F.); (G.S.); (L.T.)
- Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go Francesco Vito 1, 00168 Roma, Italy
| | - Silvia Sorrentino
- Sezione di Istologia ed Embriologia, Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Roma, Italy; (A.B.); (S.S.); (D.F.); (G.S.); (L.T.)
| | - Damon Fard
- Sezione di Istologia ed Embriologia, Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Roma, Italy; (A.B.); (S.S.); (D.F.); (G.S.); (L.T.)
| | - Elisa Lepore
- DAHFMO-Unità di Istologia ed Embriologia Medica, Sapienza Università di Roma, 00161 Roma, Italy; (E.L.); (G.D.)
| | - Gigliola Sica
- Sezione di Istologia ed Embriologia, Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Roma, Italy; (A.B.); (S.S.); (D.F.); (G.S.); (L.T.)
| | - Gabriella Dobrowolny
- DAHFMO-Unità di Istologia ed Embriologia Medica, Sapienza Università di Roma, 00161 Roma, Italy; (E.L.); (G.D.)
| | - Luca Tamagnone
- Sezione di Istologia ed Embriologia, Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Roma, Italy; (A.B.); (S.S.); (D.F.); (G.S.); (L.T.)
- Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go Francesco Vito 1, 00168 Roma, Italy
| | - Bianca Maria Scicchitano
- Sezione di Istologia ed Embriologia, Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, L.go Francesco Vito 1, 00168 Roma, Italy; (A.B.); (S.S.); (D.F.); (G.S.); (L.T.)
- Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go Francesco Vito 1, 00168 Roma, Italy
- Correspondence:
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Anderson HJ, Sahoo JK, Wells J, van Nuffel S, Dhowre HS, Oreffo ROC, Zelzer M, Ulijn RV, Dalby MJ. Cell-controlled dynamic surfaces for skeletal stem cell growth and differentiation. Sci Rep 2022; 12:8165. [PMID: 35581256 PMCID: PMC9114122 DOI: 10.1038/s41598-022-12057-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 04/22/2022] [Indexed: 11/09/2022] Open
Abstract
Skeletal stem cells (SSCs, or mesenchymal stromal cells typically referred to as mesenchymal stem cells from the bone marrow) are a dynamic progenitor population that can enter quiescence, self-renew or differentiate depending on regenerative demand and cues from their niche environment. However, ex vivo, in culture, they are grown typically on hard polystyrene surfaces, and this leads to rapid loss of the SSC phenotype. While materials are being developed that can control SSC growth and differentiation, very few examples of dynamic interfaces that reflect the plastic nature of the stem cells have, to date, been developed. Achieving such interfaces is challenging because of competing needs: growing SSCs require lower cell adhesion and intracellular tension while differentiation to, for example, bone-forming osteoblasts requires increased adhesion and intracellular tension. We previously reported a dynamic interface where the cell adhesion tripeptide arginine-glycine-aspartic acid (RGD) was presented to the cells upon activation by user-added elastase that cleaved a bulky blocking group hiding RGD from the cells. This allowed for a growth phase while the blocking group was in place and the cells could only form smaller adhesions, followed by an osteoblast differentiation phase that was induced after elastase was added which triggered exposure of RGD and subsequent cell adhesion and contraction. Here, we aimed to develop an autonomous system where the surface is activated according to the need of the cell by using matrix metalloprotease (MMP) cleavable peptide sequences to remove the blocking group with the hypothesis that the SSCs would produce higher levels of MMP as the cells reached confluence. The current studies demonstrate that SSCs produce active MMP-2 that can cleave functional groups on a surface. We also demonstrate that SSCs can grow on the uncleaved surface and, with time, produce osteogenic marker proteins on the MMP-responsive surface. These studies demonstrate the concept for cell-controlled surfaces that can modulate adhesion and phenotype with significant implications for stem cell phenotype modulation.
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Affiliation(s)
- Hilary J Anderson
- Centre for the Cellular Microenvironment, Institute of Molecular, Cell & Systems Biology, MVLS, University of Glasgow, Joseph Black Building, Glasgow, G12 8QQ, UK
| | - Jugal Kishore Sahoo
- Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, Glasgow, G1 1RD, UK
- Department of Biomedical Engineering, Science and Technology Centre, Tufts University, 4 Colby St., Medford, MA, 02155, USA
| | - Julia Wells
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK
| | - Sebastiaan van Nuffel
- School of Pharmacy, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, NG7 2RD, UK
- M4I, Faculty of Science and Engineering, Maastricht University, Maastricht, The Netherlands
| | - Hala S Dhowre
- School of Pharmacy, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, NG7 2RD, UK
- Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Richard O C Oreffo
- Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK
| | - Mischa Zelzer
- School of Pharmacy, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, NG7 2RD, UK
| | - Rein V Ulijn
- Nanoscience Initiative at Advanced Science Research Center (ASRC) of the Graduate Center of the City University of New York, New York, USA
- Department of Chemistry Hunter College, City University of New York, New York, USA
- Ph.D. Programs in Biochemistry and Chemistry, The Graduate Center of the City University of New York, New York, USA
| | - Matthew J Dalby
- Centre for the Cellular Microenvironment, Institute of Molecular, Cell & Systems Biology, MVLS, University of Glasgow, Joseph Black Building, Glasgow, G12 8QQ, UK.
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47
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Iberite F, Gruppioni E, Ricotti L. Skeletal muscle differentiation of human iPSCs meets bioengineering strategies: perspectives and challenges. NPJ Regen Med 2022; 7:23. [PMID: 35393412 PMCID: PMC8991236 DOI: 10.1038/s41536-022-00216-9] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 03/01/2022] [Indexed: 12/31/2022] Open
Abstract
Although skeletal muscle repairs itself following small injuries, genetic diseases or severe damages may hamper its ability to do so. Induced pluripotent stem cells (iPSCs) can generate myogenic progenitors, but their use in combination with bioengineering strategies to modulate their phenotype has not been sufficiently investigated. This review highlights the potential of this combination aimed at pushing the boundaries of skeletal muscle tissue engineering. First, the overall organization and the key steps in the myogenic process occurring in vivo are described. Second, transgenic and non-transgenic approaches for the myogenic induction of human iPSCs are compared. Third, technologies to provide cells with biophysical stimuli, biomaterial cues, and biofabrication strategies are discussed in terms of recreating a biomimetic environment and thus helping to engineer a myogenic phenotype. The embryonic development process and the pro-myogenic role of the muscle-resident cell populations in co-cultures are also described, highlighting the possible clinical applications of iPSCs in the skeletal muscle tissue engineering field.
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Affiliation(s)
- Federica Iberite
- The BioRobotics Institute, Scuola Superiore Sant'Anna, 56127, Pisa (PI), Italy. .,Department of Excellence in Robotics & AI, Scuola Superiore Sant'Anna, 56127, Pisa (PI), Italy.
| | - Emanuele Gruppioni
- Centro Protesi INAIL, Istituto Nazionale per l'Assicurazione contro gli Infortuni sul Lavoro, 40054, Vigorso di Budrio (BO), Italy
| | - Leonardo Ricotti
- The BioRobotics Institute, Scuola Superiore Sant'Anna, 56127, Pisa (PI), Italy.,Department of Excellence in Robotics & AI, Scuola Superiore Sant'Anna, 56127, Pisa (PI), Italy
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48
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Fischer MM, Herzel H, Blüthgen N. Mathematical modelling identifies conditions for maintaining and escaping feedback control in the intestinal epithelium. Sci Rep 2022; 12:5569. [PMID: 35368028 PMCID: PMC8976856 DOI: 10.1038/s41598-022-09202-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/17/2022] [Indexed: 02/07/2023] Open
Abstract
The intestinal epithelium is one of the fastest renewing tissues in mammals. It shows a hierarchical organisation, where intestinal stem cells at the base of crypts give rise to rapidly dividing transit amplifying cells that in turn renew the pool of short-lived differentiated cells. Upon injury and stem-cell loss, cells can also de-differentiate. Tissue homeostasis requires a tightly regulated balance of differentiation and stem cell proliferation, and failure can lead to tissue extinction or to unbounded growth and cancerous lesions. Here, we present a two-compartment mathematical model of intestinal epithelium population dynamics that includes a known feedback inhibition of stem cell differentiation by differentiated cells. The model shows that feedback regulation stabilises the number of differentiated cells as these become invariant to changes in their apoptosis rate. Stability of the system is largely independent of feedback strength and shape, but specific thresholds exist which if bypassed cause unbounded growth. When dedifferentiation is added to the model, we find that the system can recover faster after certain external perturbations. However, dedifferentiation makes the system more prone to losing homeostasis. Taken together, our mathematical model shows how a feedback-controlled hierarchical tissue can maintain homeostasis and can be robust to many external perturbations.
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Affiliation(s)
- Matthias M Fischer
- Institute for Theoretical Biology, Charité Universitätsmedizin Berlin and Humboldt Universität zu Berlin, Berlin, 10115, Germany
- Institute of Pathology, Charité Universitätsmedizin Berlinn, Berlin, 10117, Germany
| | - Hanspeter Herzel
- Institute for Theoretical Biology, Charité Universitätsmedizin Berlin and Humboldt Universität zu Berlin, Berlin, 10115, Germany
| | - Nils Blüthgen
- Institute for Theoretical Biology, Charité Universitätsmedizin Berlin and Humboldt Universität zu Berlin, Berlin, 10115, Germany.
- Institute of Pathology, Charité Universitätsmedizin Berlinn, Berlin, 10117, Germany.
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49
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Anudeep TC, Jeyaraman M, Muthu S, Rajendran RL, Gangadaran P, Mishra PC, Sharma S, Jha SK, Ahn BC. Advancing Regenerative Cellular Therapies in Non-Scarring Alopecia. Pharmaceutics 2022; 14:612. [PMID: 35335987 PMCID: PMC8953616 DOI: 10.3390/pharmaceutics14030612] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/28/2022] [Accepted: 03/07/2022] [Indexed: 02/05/2023] Open
Abstract
Alopecia or baldness is a common diagnosis in clinical practice. Alopecia can be scarring or non-scarring, diffuse or patchy. The most prevalent type of alopecia is non-scarring alopecia, with the majority of cases being androgenetic alopecia (AGA) or alopecia areata (AA). AGA is traditionally treated with minoxidil and finasteride, while AA is treated with immune modulators; however, both treatments have significant downsides. These drawbacks compel us to explore regenerative therapies that are relatively devoid of adverse effects. A thorough literature review was conducted to explore the existing proven and experimental regenerative treatment modalities in non-scarring alopecia. Multiple treatment options compelled us to classify them into growth factor-rich and stem cell-rich. The growth factor-rich group included platelet-rich plasma, stem cell-conditioned medium, exosomes and placental extract whereas adult stem cells (adipose-derived stem cell-nano fat and stromal vascular fraction; bone marrow stem cell and hair follicle stem cells) and perinatal stem cells (umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), Wharton jelly-derived MSCs (WJ-MSCs), amniotic fluid-derived MSCs (AF-MSCs), and placental MSCs) were grouped into the stem cell-rich group. Because of its regenerative and proliferative capabilities, MSC lies at the heart of regenerative cellular treatment for hair restoration. A literature review revealed that both adult and perinatal MSCs are successful as a mesotherapy for hair regrowth. However, there is a lack of standardization in terms of preparation, dose, and route of administration. To better understand the source and mode of action of regenerative cellular therapies in hair restoration, we have proposed the "À La Mode Classification". In addition, available evidence-based cellular treatments for hair regrowth have been thoroughly described.
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Affiliation(s)
- Talagavadi Channaiah Anudeep
- Department of Plastic Surgery, Topiwala National Medical College and BYL Nair Ch. Hospital, Mumbai 400008, India;
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- À La Mode Esthétique Studio, Mysuru 570011, India
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
| | - Madhan Jeyaraman
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
- Department of Orthopaedics, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, India
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624304, India
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Korea
| | - Prabhu Chandra Mishra
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
| | - Shilpa Sharma
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
- Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India; (M.J.); (S.M.); (S.K.J.)
- International Association of Stem Cell and Regenerative Medicine (IASRM), New Delhi 110092, India; (P.C.M.); (S.S.)
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Sciences, School of Medicine, Kyungpook National University, Daegu 41944, Korea
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Barhouse PS, Andrade MJ, Smith Q. Home Away From Home: Bioengineering Advancements to Mimic the Developmental and Adult Stem Cell Niche. FRONTIERS IN CHEMICAL ENGINEERING 2022. [DOI: 10.3389/fceng.2022.832754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The inherent self-organizing capacity of pluripotent and adult stem cell populations has advanced our fundamental understanding of processes that drive human development, homeostasis, regeneration, and disease progression. Translating these principles into in vitro model systems has been achieved with the advent of organoid technology, driving innovation to harness patient-specific, cell-laden regenerative constructs that can be engineered to augment or replace diseased tissue. While developmental organization and regenerative adult stem cell niches are tightly regulated in vivo, in vitro analogs lack defined architecture and presentation of physicochemical cues, leading to the unhindered arrangement of mini-tissues that lack complete physiological mimicry. This review aims to highlight the recent integrative engineering approaches that elicit spatio-temporal control of the extracellular niche to direct the structural and functional maturation of pluripotent and adult stem cell derivatives. While the advances presented here leverage multi-pronged strategies ranging from synthetic biology to microfabrication technologies, the methods converge on recreating the biochemical and biophysical milieu of the native tissue to be modeled or regenerated.
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