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Yang Y, Sokolich M, Mallick S, Das S. Quadrupole Magnetic Tweezers for Precise Cell Transportation. IEEE Trans Biomed Eng 2025; 72:1437-1444. [PMID: 40030435 DOI: 10.1109/tbme.2024.3509313] [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: 03/05/2025]
Abstract
This research introduces a quadrupole magnetic tweezers which can be used for precise cell transportation by actuating magnetic spherical microrobots. The focus of the system is on navigating and manipulating cells within environments characterized by high cellular density. Demonstrating efficacy in moving cells through densely packed cell samples, the system underscores its potential to overcome common obstacles such as inaccurate target delivery and inefficiency. The findings from this study highlight the significant promise that microrobotic technologies hold in advancing medical applications, particularly in precise cell delivery mechanisms, setting a foundation for the future exploration and utilization of medical microrobots.
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Ajekiigbe VO, Agbo CE, Ogieuhi IJ, Anthony CS, Adewole OA, Ahmed B, Akingbola A, Nwankwo CK, Kayode AT, Chima UE, Adaobi OM. Innovative approaches to treatment of eye diseases: advances in stem cell therapy use in ophthalmology. Int Ophthalmol 2025; 45:113. [PMID: 40120030 DOI: 10.1007/s10792-025-03493-7] [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: 12/04/2024] [Accepted: 03/06/2025] [Indexed: 03/25/2025]
Abstract
INTRODUCTION The human eye, a photo-sensory organ with an array of neuronal and tissue networks, remains susceptible to damage from various diseases and disorders despite its being a flawless masterpiece. It is estimated that over 2 billion people suffer from vision loss with common causative factors such as; age-related macular degeneration (AMD), glaucoma, cataracts, diabetic retinopathy, and infections amongst others. The use of Orthodox procedures has only helped mitigate the pathology; however, it doesn't serve any substantial curative purpose. More recently, the incorporation of new therapies via ocular delivery of nanomaterials and stem cell intervention has helped to change tides in the treatment of various ophthalmic pathologies. MAIN TEXT This review provides an overview of the current trends and breakthroughs in ophthalmology via stem cell therapy, with emphasis on its types, mechanisms, applications, and benefits. Mesenchymal stem cells which can arise from embryonic or adult origin possess some immunomodulatory effects that contribute to the therapeutic relevance of the MSCs and the ability to evade rejection from the host. However, the major drawback has been uncontrolled growth which can result in unintended side effects. Moreso, religious and ethical issues concerning the employment of MSCs from embryonic origin have also hindered clinical progression with its use. The use of stem cell therapy in the treatment of eye pathologies which is still undergoing clinical trials has shown to be a more viable treatment approach in ophthalmology as it targets retinal degenerative diseases thereby offering novel pathways for vision restoration. And also serves as a revolutionary alternative for treating severe ocular diseases. Stem cell delivery techniques might be quite cumbersome as the eye is a very delicate organ. The therapeutic interventional technique employed is aimed to ensure the reduction or absence of undesired effects in the deposition of the active pharmaceutical ingredient (API) being the stem cells. Techniques such as hydrogel-based injectables, which offer delivery of the APIs to the desired site of action without change in the physicochemical properties of the drug molecule, the scaffold delivery techniques, and the use of 3D bio-printing which can be used to develop scaffolds for retinal degeneration. The employment of artificial intelligence and machine learning in stem cell therapy has shown to be very fast and efficient in stem cell delivery and preventing likely human errors. CONCLUSIONS Unlike conventional treatments that often focus on managing symptoms, stem cells have the unique ability to repair and regenerate damaged tissues, addressing the root causes of the diseases. However, limitations due to economic, regulatory, and ethical challenges have posed barriers to advancing stem cell therapies.
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Affiliation(s)
| | | | | | | | | | - Bisharat Ahmed
- Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan
| | - Adewunmi Akingbola
- Department of Public Health, University of Cambridge Cambridgeshire Old Trinity Schools, Cambridge, CB2 1TN, England, UK
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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] [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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Lopes CR, Cunha RA. Impact of coffee intake on human aging: Epidemiology and cellular mechanisms. Ageing Res Rev 2024; 102:102581. [PMID: 39557300 DOI: 10.1016/j.arr.2024.102581] [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: 08/29/2024] [Revised: 11/09/2024] [Accepted: 11/12/2024] [Indexed: 11/20/2024]
Abstract
The conception of coffee consumption has undergone a profound modification, evolving from a noxious habit into a safe lifestyle actually preserving human health. The last 20 years also provided strikingly consistent epidemiological evidence showing that the regular consumption of moderate doses of coffee attenuates all-cause mortality, an effect observed in over 50 studies in different geographic regions and different ethnicities. Coffee intake attenuates the major causes of mortality, dampening cardiovascular-, cerebrovascular-, cancer- and respiratory diseases-associated mortality, as well as some of the major causes of functional deterioration in the elderly such as loss of memory, depression and frailty. The amplitude of the benefit seems discrete (17 % reduction) but nonetheless corresponds to an average increase in healthspan of 1.8 years of lifetime. This review explores evidence from studies in humans and human tissues supporting an ability of coffee and of its main components (caffeine and chlorogenic acids) to preserve the main biological mechanisms responsible for the aging process, namely genomic instability, macromolecular damage, metabolic and proteostatic impairments with particularly robust effects on the control of stress adaptation and inflammation and unclear effects on stem cells and regeneration. Further studies are required to detail these mechanistic benefits in aged individuals, which may offer new insights into understanding of the biology of aging and the development of new senostatic strategies. Additionally, the safety of this lifestyle factor in the elderly prompts a renewed attention to recommending the maintenance of coffee consumption throughout life as a healthy lifestyle and to further exploring who gets the greater benefit with what schedules of which particular types and doses of coffee.
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Affiliation(s)
- Cátia R Lopes
- CNC-Center for Neuroscience and Cell Biology, Portugal; Faculty of Medicine, Portugal
| | - Rodrigo A Cunha
- CNC-Center for Neuroscience and Cell Biology, Portugal; Faculty of Medicine, Portugal; MIA-Portugal, Multidisciplinary Institute of Aging, University of Coimbra, Portugal; Centro de Medicina Digital P5, Escola de Medicina da Universidade do Minho, Braga, Portugal.
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Górska A, Trubalski M, Borowski B, Brachet A, Szymańczyk S, Markiewicz R. Navigating stem cell culture: insights, techniques, challenges, and prospects. Front Cell Dev Biol 2024; 12:1435461. [PMID: 39588275 PMCID: PMC11586186 DOI: 10.3389/fcell.2024.1435461] [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] [Received: 06/03/2024] [Accepted: 10/09/2024] [Indexed: 11/27/2024] Open
Abstract
Stem cell research holds huge promise for regenerative medicine and disease modeling, making the understanding and optimization of stem cell culture a critical aspect of advancing these therapeutic applications. This comprehensive review provides an in-depth overview of stem cell culture, including general information, contemporary techniques, encountered problems, and future perspectives. The article begins by explaining the fundamental characteristics of various stem cell types, elucidating the importance of proper culture conditions in maintaining pluripotency or lineage commitment. A detailed exploration of established culture techniques sheds light on the evolving landscape of stem cell culture methodologies. Common challenges such as genetic stability, heterogeneity, and differentiation efficiency are thoroughly discussed, with insights into cutting-edge strategies and technologies aimed at addressing these hurdles. Moreover, the article delves into the impact of substrate materials, culture media components, and biophysical cues on stem cell behavior, emphasizing the intricate interplay between the microenvironment and cell fate decisions. As stem cell research advances, ethical considerations and regulatory frameworks become increasingly important, prompting a critical examination of these aspects in the context of culture practices. Lastly, the article explores emerging perspectives, including the integration of artificial intelligence and machine learning in optimizing culture conditions, and the potential applications of stem cell-derived products in personalized medicine. This comprehensive overview aims to serve as a valuable resource for researchers and clinicians, fostering a deeper understanding of stem cell culture and its key role in advancing regenerative medicine and biomedical research.
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Affiliation(s)
- Aleksandra Górska
- Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, Lublin, Poland
| | - Mateusz Trubalski
- Students Scientific Association, Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, Lublin, Poland
| | - Bartosz Borowski
- Students Scientific Association, Department of Normal, Clinical and Imaging Anatomy, Medical University of Lublin, Lublin, Poland
| | - Adam Brachet
- Student Scientific Association, Department of Forensic Medicine, Medical University of Lublin, Lublin, Poland
| | - Sylwia Szymańczyk
- Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Lublin, Poland
| | - Renata Markiewicz
- Occupational Therapy Laboratory, Chair of Nursing Development, Medical University of Lublin, Lublin, Poland
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Li J, Deng T, Zhu S, Xie P, Wang W, Zhou H, Xu C. The SDF-1/CXCR4 axis is involved in adipose-derived stem cell migration. Neurourol Urodyn 2024; 43:2279-2289. [PMID: 39149821 DOI: 10.1002/nau.25571] [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: 12/06/2023] [Revised: 06/27/2024] [Accepted: 06/28/2024] [Indexed: 08/17/2024]
Abstract
BACKGROUND Intravenous injection of adipose-derived stem cells (ADSCs) can improve the urinary function of stress urinary incontinence (SUI) model rats and C-X-C chemokine receptor type 4 (CXCR4)-positive ADSCs are found in urethral tissues. The CXCR4 ligand stromal cell-derived factor-1 (SDF-1) is highly expressed in urinary incontinence model rats. In this study, we investigated the involvement of the SDF-1/CXCR4 axis in the homing of ADSCs. METHODS ADSCs were isolated from rats and purified. The levels of CXCR4 and CXCR7 were determined by western blot analysis and immunofluorescence assays following stimulation with SDF-1. Hypoxia conditioning was performed to treat the cells in vitro, following which the messenger RNA (mRNA) and protein level of SDF-1, CXCR4, and CXCR7 were estimated. RESULTS We found that CXCR4 and CXCR7 were expressed in ADSCs at passage zero (P0), P1, and P3, and the expression of both increased after SDF-1 stimulation. The level of expression of the mRNAs and proteins of SDF-1, CXCR4, and CXCR7 in ADSCs was higher after hypoxic conditioning. We then knocked down CXCR4 or CXCR7 using small interfering RNAs and found that the mRNA levels of CXCR4 and CXCR7 were considerably downregulated in the si-CXCR4/7-transfected cells. We also found that the SDF-1/CXCR4 axis was required for the migration of ADSCs. The phosphorylation levels of Janus kinase (JAK), protein kinase B (AKT), and extracellular regulated protein kinase significantly increased in SDF-1-stimulated ADSCs. However, the migration of ADSCs was suppressed when the corresponding specific inhibitors were used to block JAK and AKT signaling or silence CXCR4, whereas no significant change was observed in the migratory ability of ADSCs when the ERK pathway was blocked or CXCR7 was silenced. CONCLUSIONS The SDF-1/CXCR4 axis is involved in the migration of ADSCs and may play a role in the migrate of ADSCs in SUI.
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Affiliation(s)
- Jiang Li
- The Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing, China
| | - Tibin Deng
- The Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing, China
| | - Shaojie Zhu
- The Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing, China
| | - Pingbo Xie
- The Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing, China
| | - Wei Wang
- The Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing, China
| | - Hongqing Zhou
- The Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing, China
| | - Chenxiang Xu
- The Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing, China
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Zheng F, Tian R, Lu H, Liang X, Shafiq M, Uchida S, Chen H, Ma M. Droplet Microfluidics Powered Hydrogel Microparticles for Stem Cell-Mediated Biomedical Applications. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2401400. [PMID: 38881184 DOI: 10.1002/smll.202401400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 05/21/2024] [Indexed: 06/18/2024]
Abstract
Stem cell-related therapeutic technologies have garnered significant attention of the research community for their multi-faceted applications. To promote the therapeutic effects of stem cells, the strategies for cell microencapsulation in hydrogel microparticles have been widely explored, as the hydrogel microparticles have the potential to facilitate oxygen diffusion and nutrient transport alongside their ability to promote crucial cell-cell and cell-matrix interactions. Despite their significant promise, there is an acute shortage of automated, standardized, and reproducible platforms to further stem cell-related research. Microfluidics offers an intriguing platform to produce stem cell-laden hydrogel microparticles (SCHMs) owing to its ability to manipulate the fluids at the micrometer scale as well as precisely control the structure and composition of microparticles. In this review, the typical biomaterials and crosslinking methods for microfluidic encapsulation of stem cells as well as the progress in droplet-based microfluidics for the fabrication of SCHMs are outlined. Moreover, the important biomedical applications of SCHMs are highlighted, including regenerative medicine, tissue engineering, scale-up production of stem cells, and microenvironmental simulation for fundamental cell studies. Overall, microfluidics holds tremendous potential for enabling the production of diverse hydrogel microparticles and is worthy for various stem cell-related biomedical applications.
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Affiliation(s)
- Fangqiao Zheng
- School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, P. R. China
| | - Ruizhi Tian
- Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Hongxu Lu
- Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Xiao Liang
- School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, P. R. China
| | - Muhammad Shafiq
- Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan
| | - Satoshi Uchida
- Innovation Center of NanoMedicine (iCONM), Kawasaki Institute of Industrial Promotion, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan
- Department of Advanced Nanomedical Engineering, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8510, Japan
| | - Hangrong Chen
- School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, P. R. China
- Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Ming Ma
- School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, P. R. China
- Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
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Yu Y, Andreev AY, Rogovaya OS, Subbot AM, Domogatsky SP, Avetisov SE, Vorotelyak EA, Osidak EO. Matrix-Assisted Cell Transplantation for the Treatment of Limbal Stem Cell Deficiency in a Rabbit Model. Biomedicines 2024; 12:101. [PMID: 38255207 PMCID: PMC10813050 DOI: 10.3390/biomedicines12010101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 12/26/2023] [Accepted: 12/28/2023] [Indexed: 01/24/2024] Open
Abstract
With the development of regenerative medicine in ophthalmology, the identification of cells with high proliferative potential in the limbal area has attracted the attention of ophthalmologists and offered a new option for treatment in clinical practice. Limbal stem cell deficiency (LSCD) is an identified eye disease with a difficult and negative outcome, for which the traditional treatment is keratoplasty. This study sought to evaluate the efficacy of matrix-assisted cell transplantation consisting of in vitro-cultured autologous limbal stem cells (LSCs) and type I collagen for the treatment of LSCD in rabbits. LSCD was induced in 10 rabbits by a combination of mechanical limbectomy and alkali burns. Cells were cultured on a plate for 14 days before being transferred to a collagen-based matrix for another 7 days. Rabbits were divided into two groups as follows: the experimental group (five rabbits) received matrix-assisted cell transplantation, while the control group (five rabbits) received only conservative therapy with anti-inflammatory eye drops. During the postoperative period, all rabbits were examined using slit-lamp biomicroscopy with photo-registration and fluorescent staining, impression cytology and anterior segment optical coherence tomography (AS-OCT). Rabbits were euthanized at 30 and 120 days, and their corneas were processed for histology and immunohistochemistry. As a consequence, rabbits in the experimental group demonstrated the restoration of the corneal epithelium and transparency without epithelial defects. Moreover, goblet cells were absent in the central zone of the corneal epithelium. In conclusion, our new method of treatment enhanced the corneal surface and is an effective method of treatment for LSCD in rabbits.
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Affiliation(s)
- Yang Yu
- Department of Eye Diseases, I.M. Sechenov First Moscow State Medical University, 8-2, Trubetskaya Street, 119991 Moscow, Russia
| | - Andrey Yurevich Andreev
- Department of Eye Diseases, I.M. Sechenov First Moscow State Medical University, 8-2, Trubetskaya Street, 119991 Moscow, Russia
- Department of Pathologies of Optical Medium of the Eye, Krasnov Research Institute of Eye Diseases, 11A Rossolimo St., 119021 Moscow, Russia
- R&D Department, Imtek Ltd., 3rd Cherepkovskaya 15A, 121552 Moscow, Russia;
| | - Olga Sergeevna Rogovaya
- Laboratory of Cell Biology, Koltzov Institute of Developmental Biology Russian Academy of Science, 26, Vavilova St., 119334 Moscow, Russia
| | - Anastasia Mikhailovna Subbot
- Laboratory of Basic Research in Ophthalmology, Krasnov Research Institute of Eye Diseases, 11A Rossolimo St., 119021 Moscow, Russia
| | - Sergey Petrovich Domogatsky
- R&D Department, Imtek Ltd., 3rd Cherepkovskaya 15A, 121552 Moscow, Russia;
- Laboratory of Immunochemistry, FSBI National Medical Research Centre of Cardiology Name after Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Academika Chazova St., 15A, 121552 Moscow, Russia
| | - Sergey Eduardovich Avetisov
- Department of Eye Diseases, I.M. Sechenov First Moscow State Medical University, 8-2, Trubetskaya Street, 119991 Moscow, Russia
- Department of Pathologies of Optical Medium of the Eye, Krasnov Research Institute of Eye Diseases, 11A Rossolimo St., 119021 Moscow, Russia
| | - Ekaterina Andreevna Vorotelyak
- Laboratory of Cell Biology, Koltzov Institute of Developmental Biology Russian Academy of Science, 26, Vavilova St., 119334 Moscow, Russia
| | - Egor Olegovich Osidak
- R&D Department, Imtek Ltd., 3rd Cherepkovskaya 15A, 121552 Moscow, Russia;
- Laboratory of Cellular Hemostasis and Thrombosis, Dmitry Rogachev National Medical Research Center of Paediatric Haematology, Oncology and Immunology, Samora Machel St., 1, 117997 Moscow, Russia
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Dhanjal DS, Singh R, Sharma V, Nepovimova E, Adam V, Kuca K, Chopra C. Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine. Curr Med Chem 2024; 31:1646-1690. [PMID: 37138422 DOI: 10.2174/0929867330666230503144619] [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: 11/12/2022] [Revised: 03/13/2023] [Accepted: 03/16/2023] [Indexed: 05/05/2023]
Abstract
The foundations of cell reprogramming were laid by Yamanaka and co-workers, who showed that somatic cells can be reprogrammed into pluripotent cells (induced pluripotency). Since this discovery, the field of regenerative medicine has seen advancements. For example, because they can differentiate into multiple cell types, pluripotent stem cells are considered vital components in regenerative medicine aimed at the functional restoration of damaged tissue. Despite years of research, both replacement and restoration of failed organs/ tissues have remained elusive scientific feats. However, with the inception of cell engineering and nuclear reprogramming, useful solutions have been identified to counter the need for compatible and sustainable organs. By combining the science underlying genetic engineering and nuclear reprogramming with regenerative medicine, scientists have engineered cells to make gene and stem cell therapies applicable and effective. These approaches have enabled the targeting of various pathways to reprogramme cells, i.e., make them behave in beneficial ways in a patient-specific manner. Technological advancements have clearly supported the concept and realization of regenerative medicine. Genetic engineering is used for tissue engineering and nuclear reprogramming and has led to advances in regenerative medicine. Targeted therapies and replacement of traumatized , damaged, or aged organs can be realized through genetic engineering. Furthermore, the success of these therapies has been validated through thousands of clinical trials. Scientists are currently evaluating induced tissue-specific stem cells (iTSCs), which may lead to tumour-free applications of pluripotency induction. In this review, we present state-of-the-art genetic engineering that has been used in regenerative medicine. We also focus on ways that genetic engineering and nuclear reprogramming have transformed regenerative medicine and have become unique therapeutic niches.
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Affiliation(s)
- Daljeet Singh Dhanjal
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India
| | - Reena Singh
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India
| | - Varun Sharma
- Head of Bioinformatic Division, NMC Genetics India Pvt. Ltd., Gurugram, India
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, 50003, Czech Republic
| | - Vojtech Adam
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno, CZ 613 00, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic
| | - Kamil Kuca
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, 50003, Czech Republic
- Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, 50005, Czech Republic
| | - Chirag Chopra
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India
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Yang H, Yao L, Wang Y, Chen G, Chen H. Advancing cell surface modification in mammalian cells with synthetic molecules. Chem Sci 2023; 14:13325-13345. [PMID: 38033886 PMCID: PMC10685406 DOI: 10.1039/d3sc04597h] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 10/30/2023] [Indexed: 12/02/2023] Open
Abstract
Biological cells, being the fundamental entities of life, are widely acknowledged as intricate living machines. The manipulation of cell surfaces has emerged as a progressively significant domain of investigation and advancement in recent times. Particularly, the alteration of cell surfaces using meticulously crafted and thoroughly characterized synthesized molecules has proven to be an efficacious means of introducing innovative functionalities or manipulating cells. Within this realm, a diverse array of elegant and robust strategies have been recently devised, including the bioorthogonal strategy, which enables selective modification. This review offers a comprehensive survey of recent advancements in the modification of mammalian cell surfaces through the use of synthetic molecules. It explores a range of strategies, encompassing chemical covalent modifications, physical alterations, and bioorthogonal approaches. The review concludes by addressing the present challenges and potential future opportunities in this rapidly expanding field.
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Affiliation(s)
- He Yang
- College of Chemistry, Chemical Engineering and Materials Science, Soochow University 199 Ren'ai Road Suzhou 215123 Jiangsu P. R. China
| | - Lihua Yao
- College of Chemistry, Chemical Engineering and Materials Science, Soochow University 199 Ren'ai Road Suzhou 215123 Jiangsu P. R. China
| | - Yichen Wang
- College of Chemistry, Chemical Engineering and Materials Science, Soochow University 199 Ren'ai Road Suzhou 215123 Jiangsu P. R. China
| | - Gaojian Chen
- College of Chemistry, Chemical Engineering and Materials Science, Soochow University 199 Ren'ai Road Suzhou 215123 Jiangsu P. R. China
- Center for Soft Condensed Matter Physics and Interdisciplinary Research, Soochow University Suzhou 215006 Jiangsu P. R. China
| | - Hong Chen
- College of Chemistry, Chemical Engineering and Materials Science, Soochow University 199 Ren'ai Road Suzhou 215123 Jiangsu P. R. China
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Sokolich M, Mallick S, Shah ZH, Yang Y, Das S. Cellular Cargo Manipulation Using Magnetically Steerable Microrobots in Dense Environments. PROCEEDINGS OF THE 2023 6TH INTERNATIONAL CONFERENCE ON ADVANCES IN ROBOTICS. AIR 2023: ADVANCES IN ROBOTICS - 6TH INTERNATIONAL CONFERENCE OF THE ROBOTICS SOCIETY 2023 2023; 2023:20. [PMID: 39629043 PMCID: PMC11614068 DOI: 10.1145/3610419.3610439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/06/2024]
Abstract
This study presents a microrobotic system that utilizes magnetic Janus microrobots and a 3D-printed magnetic tweezers setup controlled by electromagnetic coils to transport cells in a densely crowded environment. The system was successfully demonstrated to transport cells in a densely populated sample of cells. The results indicate that this microrobotic system could address challenges such as off-target delivery, thereby realizing the full potential of medical microrobots for this and other applications. This study represents an important step towards developing a more efficient and effective method for targeted drug delivery in the field of medicine.
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Affiliation(s)
| | | | | | - Yanda Yang
- University of Delaware, Newark, Delaware, USA
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12
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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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13
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The Exciting Realities and Possibilities of iPS-Derived Cardiomyocytes. Bioengineering (Basel) 2023; 10:bioengineering10020237. [PMID: 36829731 PMCID: PMC9952364 DOI: 10.3390/bioengineering10020237] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/03/2023] [Accepted: 02/09/2023] [Indexed: 02/12/2023] Open
Abstract
Induced pluripotent stem cells (iPSCs) have become a prevalent topic after their discovery, advertised as an ethical alternative to embryonic stem cells (ESCs). Due to their ability to differentiate into several kinds of cells, including cardiomyocytes, researchers quickly realized the potential for differentiated cardiomyocytes to be used in the treatment of heart failure, a research area with few alternatives. This paper discusses the differentiation process for human iPSC-derived cardiomyocytes and the possible applications of said cells while answering some questions regarding ethical issues.
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14
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Cha Y, Park TY, Leblanc P, Kim KS. Current Status and Future Perspectives on Stem Cell-Based Therapies for Parkinson's Disease. J Mov Disord 2023; 16:22-41. [PMID: 36628428 PMCID: PMC9978267 DOI: 10.14802/jmd.22141] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 10/15/2022] [Accepted: 10/29/2022] [Indexed: 01/12/2023] Open
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting 1%-2% of the population over the age of 65. As the population ages, it is anticipated that the burden on society will significantly escalate. Although symptom reduction by currently available pharmacological and/or surgical treatments improves the quality of life of many PD patients, there are no treatments that can slow down, halt, or reverse disease progression. Because the loss of a specific cell type, midbrain dopamine neurons in the substantia nigra, is the main cause of motor dysfunction in PD, it is considered a promising target for cell replacement therapy. Indeed, numerous preclinical and clinical studies using fetal cell transplantation have provided proof of concept that cell replacement therapy may be a viable therapeutic approach for PD. However, the use of human fetal cells remains fraught with controversy due to fundamental ethical, practical, and clinical limitations. Groundbreaking work on human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, coupled with extensive basic research in the stem cell field offers promising potential for hPSC-based cell replacement to become a realistic treatment regimen for PD once several major issues can be successfully addressed. In this review, we will discuss the prospects and challenges of hPSC-based cell therapy for PD.
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Affiliation(s)
- Young Cha
- Department of Psychiatry and Molecular Neurobiology Laboratory, McLean Hospital and Program in Neuroscience, Harvard Medical School, Belmont, MA, USA
| | - Tae-Yoon Park
- Department of Psychiatry and Molecular Neurobiology Laboratory, McLean Hospital and Program in Neuroscience, Harvard Medical School, Belmont, MA, USA
| | - Pierre Leblanc
- Department of Psychiatry and Molecular Neurobiology Laboratory, McLean Hospital and Program in Neuroscience, Harvard Medical School, Belmont, MA, USA
| | - Kwang-Soo Kim
- Department of Psychiatry and Molecular Neurobiology Laboratory, McLean Hospital and Program in Neuroscience, Harvard Medical School, Belmont, MA, USA
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15
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Ma C, Han L, Wu J, Tang F, Deng Q, He T, Wu Z, Ma C, Huang W, Huang R, Pan G. MSCs cell fates in murine acute liver injury and chronic liver fibrosis induced by carbon tetrachloride. Drug Metab Dispos 2022; 50:DMD-AR-2022-000958. [PMID: 35882404 DOI: 10.1124/dmd.122.000958] [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: 05/28/2022] [Revised: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 11/22/2022] Open
Abstract
Mesenchymal stem cells (MSCs) therapy has shown potential benefits in multiple diseases. However, their clinic performance is not as satisfactory as expected. This study aimed to provide an alternative explanation by comparing MSCs' fates in different liver diseases. The distribution and therapeutic effects of hMSCs were investigated in acute liver injury (ALI) and chronic liver fibrosis (CLF) mice models, respectively. The two models were induced by single or repeated injection of carbon tetrachloride (CCl4) separately. The increase of hMSCs exposure in the liver (AUCliver 0-72 h) were more significant in ALI than in CLF (177.1% vs. 96.2%). In the ALI model, the hMSCs exposures in the lung (AUClung 0-72 h) increased by nearly 50% while decreased by 60.7% in CLF. The efficacy satellite study indicated that hMSCs could significantly ameliorate liver injury in ALI, but its effects in CLF were limited. In the ALI, suppressed Natural Killer (NK) cell activities were observed, while NK cell activities were increased in CLF. The depletion of NK cells could increase hMSCs exposure in mice. For mice MSC (mMSCs), their cell fates in ALI were very similar to hMSCs in ALI: mMSCs' exposure in the liver and lung increased in ALI. In conclusion, our study revealed the distinct cell pharmacokinetic patterns of MSCs in ALI and CLF mice, which might be at least partially attributed to the different NK cell activities in the two liver diseases. This finding provided a novel insight into the varied MSCs' therapeutic efficacy in the clinic. Significance Statement Currently, there is little knowledge about the PK behavior of cell products like MSCs. This study was the first time investigating the influence of liver diseases on cell fates and efficacies of MSCs and the underneath rationale. The exposure was distinct between two representative liver disease models, which directly linked with the therapeutic performance that MSCs achieved. The difference could be attributed to the NK cells-mediated MSCs clearance.
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Affiliation(s)
- Chenhui Ma
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences,University of Chinese Academy of Sciences, China
| | - Li Han
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China
| | - Jiajun Wu
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China
| | - Feng Tang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences,University of Chinese Academy of Sciences, China
| | - Qiangqiang Deng
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China
| | - Ting He
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences,School of Pharmaceutical Sciences, Nanjing Tech University, China
| | - Zhitao Wu
- Shanghai Institute of Materia Medica; Nanjing University of Chinese Medicine, China
| | - Chen Ma
- Shanghai Institute of Materia Medica, China
| | - Wei Huang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences,University of Chinese Academy of Sciences, China
| | - Ruimin Huang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences,University of Chinese Academy of Sciences, China
| | - Guoyu Pan
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences,University of Chinese Academy of Sciences, China
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16
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Kwack KH, Lee HW. Clinical Potential of Dental Pulp Stem Cells in Pulp Regeneration: Current Endodontic Progress and Future Perspectives. Front Cell Dev Biol 2022; 10:857066. [PMID: 35478967 PMCID: PMC9035692 DOI: 10.3389/fcell.2022.857066] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 03/18/2022] [Indexed: 12/12/2022] Open
Abstract
Dental caries is a common disease that not only destroys the rigid structure of the teeth but also causes pulp necrosis in severe cases. Once pulp necrosis has occurred, the most common treatment is to remove the damaged pulp tissue, leading to a loss of tooth vitality and increased tooth fragility. Dental pulp stem cells (DPSCs) isolated from pulp tissue exhibit mesenchymal stem cell-like characteristics and are considered ideal candidates for regenerating damaged dental pulp tissue owing to their multipotency, high proliferation rate, and viability after cryopreservation. Importantly, DPSCs do not elicit an allogeneic immune response because they are non-immunogenic and exhibit potent immunosuppressive properties. Here, we provide an up-to-date review of the clinical applicability and potential of DPSCs, as well as emerging trends in the regeneration of damaged pulp tissue. In addition, we suggest the possibility of using DPSCs as a resource for allogeneic transplantation and provide a perspective for their clinical application in pulp regeneration.
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Affiliation(s)
- Kyu Hwan Kwack
- Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
| | - Hyeon-Woo Lee
- Department of Pharmacology, School of Dentistry, Graduate School, Institute of Oral Biology, Kyung Hee University, Seoul, South Korea
- *Correspondence: Hyeon-Woo Lee,
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17
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Puranik N, Arukha AP, Yadav SK, Yadav D, Jin JO. Exploring the Role of Stem Cell Therapy in Treating Neurodegenerative Diseases: Challenges and Current Perspectives. Curr Stem Cell Res Ther 2022; 17:113-125. [PMID: 35135462 DOI: 10.2174/1574888x16666210810103838] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/18/2021] [Accepted: 06/01/2021] [Indexed: 11/22/2022]
Abstract
:
Several human neurological disorders, such as Parkinson’s disease, Alzheimer’s disease,
amyotrophic lateral sclerosis, Huntington’s disease, spinal cord injury, multiple sclerosis, and brain
stroke, are caused by the injury to neurons or glial cells. The recent years have witnessed the successful
generation of neurons and glia cells driving efforts to develop stem-cell-based therapies for
patients to combat a broad spectrum of human neurological diseases. The inadequacy of suitable
cell types for cell replacement therapy in patients suffering from neurological disorders has hampered
the development of this promising therapeutic approach. Attempts are thus being made to reconstruct
viable neurons and glial cells from different stem cells, such as embryonic stem cells,
mesenchymal stem cells, and neural stem cells. Dedicated research to cultivate stem cell-based
brain transplantation therapies has been carried out. We aim at compiling the breakthroughs in the
field of stem cell-based therapy for the treatment of neurodegenerative maladies, emphasizing the
shortcomings faced, victories achieved, and the future prospects of the therapy in clinical settings.
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Affiliation(s)
- Nidhi Puranik
- Department of Biological Science, Bharathiar University, Coimbatore, Tamil Nadu-641046, India
| | - Ananta Prasad Arukha
- Comparative Diagnostic
and Population Medicine, College of Veterinary Medicine, University of Florida, Gainesville- 32608, U.S.A
| | - Shiv Kumar Yadav
- Department of Botany, Government Lal Bahadur Shastri PG college, Sironj, Vidisha, Madhya Pradesh, India
| | - Dhananjay Yadav
- Department of Medical Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea
| | - Jun O. Jin
- Department
of Medical Biotechnology, Yeungnam University, Gyeongsan 712-749, Korea
- Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Korea
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18
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Eleftheriadou D, Evans RE, Atkinson E, Abdalla A, Gavins FKH, Boyd AS, Williams GR, Knowles JC, Roberton VH, Phillips JB. An alginate-based encapsulation system for delivery of therapeutic cells to the CNS. RSC Adv 2022; 12:4005-4015. [PMID: 35425456 PMCID: PMC8981497 DOI: 10.1039/d1ra08563h] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 01/22/2022] [Indexed: 12/21/2022] Open
Abstract
Treatment options for neurodegenerative conditions such as Parkinson's disease have included the delivery of cells which release dopamine or neurotrophic factors to the brain. Here, we report the development of a novel approach for protecting cells after implantation into the central nervous system (CNS), by developing dual-layer alginate beads that encapsulate therapeutic cells and release an immunomodulatory compound in a sustained manner. An optimal alginate formulation was selected with a view to providing a sustained physical barrier between engrafted cells and host tissue, enabling exchange of small molecules while blocking components of the host immune response. In addition, a potent immunosuppressant, FK506, was incorporated into the outer layer of alginate beads using electrosprayed poly-ε-caprolactone core–shell nanoparticles with prolonged release profiles. The stiffness, porosity, stability and ability of the alginate beads to support and protect encapsulated SH-SY5Y cells was demonstrated, and the release profile of FK506 and its effect on T-cell proliferation in vitro was characterized. Collectively, our results indicate this multi-layer encapsulation technology has the potential to be suitable for use in CNS cell delivery, to protect implanted cells from host immune responses whilst providing permeability to nutrients and released therapeutic molecules. Novel composite cell encapsulation system: dual-layer, micro-scale beads maintain cell survival while releasing immunomodulatory FK506 in a sustained manner. This biotechnology platform could be applicable for treatment of CNS and other disorders.![]()
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Affiliation(s)
- Despoina Eleftheriadou
- UCL Centre for Nerve Engineering, University College London London UK.,UCL School of Pharmacy, University College London London WC1N 1AX UK
| | - Rachael E Evans
- UCL Centre for Nerve Engineering, University College London London UK.,UCL School of Pharmacy, University College London London WC1N 1AX UK
| | - Emily Atkinson
- UCL Centre for Nerve Engineering, University College London London UK.,UCL School of Pharmacy, University College London London WC1N 1AX UK
| | - Ahmed Abdalla
- UCL Centre for Nerve Engineering, University College London London UK.,UCL School of Pharmacy, University College London London WC1N 1AX UK
| | - Francesca K H Gavins
- UCL Centre for Nerve Engineering, University College London London UK.,UCL School of Pharmacy, University College London London WC1N 1AX UK
| | - Ashleigh S Boyd
- UCL Institute of Immunity and Transplantation, Royal Free Hospital London UK
| | - Gareth R Williams
- UCL School of Pharmacy, University College London London WC1N 1AX UK
| | - Jonathan C Knowles
- Biomaterials & Tissue Engineering, UCL Eastman Dental Institute London UK
| | - Victoria H Roberton
- UCL Centre for Nerve Engineering, University College London London UK.,UCL School of Pharmacy, University College London London WC1N 1AX UK
| | - James B Phillips
- UCL Centre for Nerve Engineering, University College London London UK.,UCL School of Pharmacy, University College London London WC1N 1AX UK
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19
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Lee CS, Kim J, Cho HJ, Kim HS. Cardiovascular Regeneration via Stem Cells and Direct Reprogramming: A Review. Korean Circ J 2022; 52:341-353. [PMID: 35502566 PMCID: PMC9064703 DOI: 10.4070/kcj.2022.0005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/16/2022] [Accepted: 02/22/2022] [Indexed: 11/24/2022] Open
Abstract
Despite recent advancements in treatment strategies, cardiovascular disease such as heart failure remains a significant source of global mortality. Stem cell technology and cellular reprogramming are rapidly growing fields that will continue to prove useful in cardiac regenerative therapeutics. This review provides information on the role of human pluripotent stem cells (hPSCs) in cardiac regeneration and discusses the practical applications of hPSC-derived cardiomyocytes (CMCs). Moreover, we discuss the practical applications of hPSC-derived CMCs while outlining the relevance of directly-reprogrammed CMCs in regenerative medicine. This review critically summarizes the most recent advances in the field will help to guide future research in this developing area. Cardiovascular disease (CVD) is the leading causes of morbidity and death globally. In particular, a heart failure remains a major problem that contributes to global mortality. Considerable advancements have been made in conventional pharmacological therapies and coronary intervention surgery for cardiac disorder treatment. However, more than 15% of patients continuously progress to end-stage heart failure and eventually require heart transplantation. Over the past year, numerous numbers of protocols to generate cardiomyocytes (CMCs) from human pluripotent stem cells (hPSCs) have been developed and applied in clinical settings. Number of studies have described the therapeutic effects of hPSCs in animal models and revealed the underlying repair mechanisms of cardiac regeneration. In addition, biomedical engineering technologies have improved the therapeutic potential of hPSC-derived CMCs in vivo. Recently substantial progress has been made in driving the direct differentiation of somatic cells into mature CMCs, wherein an intermediate cellular reprogramming stage can be bypassed. This review provides information on the role of hPSCs in cardiac regeneration and discusses the practical applications of hPSC-derived CMCs; furthermore, it outlines the relevance of directly reprogrammed CMCs in regenerative medicine.
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Affiliation(s)
- Choon-Soo Lee
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
- Strategic Center of Cell & Bio Therapy, Seoul National University Hospital, Seoul, Korea
| | - Joonoh Kim
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
- Strategic Center of Cell & Bio Therapy, Seoul National University Hospital, Seoul, Korea
| | - Hyun-Jai Cho
- Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Hyo-Soo Kim
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
- Strategic Center of Cell & Bio Therapy, Seoul National University Hospital, Seoul, Korea
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea
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20
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Li J, Chen Y, Ouyang S, Ma J, Sun H, Luo L, Chen S, Liu Y. Generation and Staging of Human Retinal Organoids Based on Self-Formed Ectodermal Autonomous Multi-Zone System. Front Cell Dev Biol 2021; 9:732382. [PMID: 34631711 PMCID: PMC8493070 DOI: 10.3389/fcell.2021.732382] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 09/03/2021] [Indexed: 01/12/2023] Open
Abstract
Methods for stem cell-derived, three-dimensional retinal organoids induction have been established and shown great potential for retinal development modeling and drug screening. Herein, we reported an exogenous-factors-free and robust method to generate retinal organoids based on “self-formed ectodermal autonomous multi-zone” (SEAM) system, a two-dimensional induction scheme that can synchronously generate multiple ocular cell lineages. Characterized by distinct morphological changes, the differentiation of the obtained retinal organoids could be staged into the early and late differentiation phases. During the early differentiation stage, retinal ganglion cells, cone photoreceptor cells (PRs), amacrine cells, and horizontal cells developed; whereas rod PRs, bipolar cells, and Müller glial cells were generated in the late differentiation phase, resembling early-phase and late-phase retinogenesis in vivo. Additionally, we modified the maintenance strategy for the retinal organoids and successfully promoted their long-term survival. Using 3D immunofluorescence image reconstruction and transmission electron microscopy, the substantial mature PRs with outer segment, inner segment and ribbon synapse were demonstrated. Besides, the retinal pigment epithelium (RPE) was induced with distinct boundary and the formation of ciliary margin was observed by co-suspending retina organoids with the zone containing RPE. The obtained RPE could be expanded and displayed similar marker expression, ultrastructural feature and functional phagocytosis to native RPE. Thus, this research described a simple and robust system which enabled generation of retina organoids with substantial mature PRs, RPE and the ciliary margin without the need of exogenous factors, providing a new platform for research of retinogenesis and retinal translational application.
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Affiliation(s)
- Jinyan Li
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Yijia Chen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Shuai Ouyang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Jingyu Ma
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Hui Sun
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Lixia Luo
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Shuyi Chen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Yizhi Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
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21
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Rawash MA, Mohamed AS, El-Zayat EM. The concurrent therapeutic potential of adipose-derived mesenchymal stem cells on Gentamycin-induced hepatorenal toxicity in rats. Curr Stem Cell Res Ther 2021; 17:808-814. [PMID: 34635044 DOI: 10.2174/1574888x16666211011124154] [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: 05/21/2021] [Revised: 07/24/2021] [Accepted: 08/05/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Adipose mesenchymal stem cells (AMSCs) are a type of stem cell employed to repair damaged organs. This study aimed to see how effective AMSCs are at treating gentamycin-induced hepatorenal damage in rats. METHODS 18 male Wister rats were assigned into three groups; control, Gentamycin (GM), and GM+AMSCs. GM induced hepatorenal toxicity through daily injection (100 mg/kg, i.p.) for eight days. On day 9, AMSC (106 cells/ml/rat) was injected intravenously. RESULTS Creatinine, urea, uric acid, AST, ALP, ALT, TNF-, and MDA levels decreased, whereas IL-10, GSH, and CAT levels increased, indicating the therapeutic potency of intravenous injection AMSCs. CONCLUSION The current study demonstrated the simultaneous therapeutic efficacy of adipose mesenchymal stem cells on the liver and kidney in the treatment of Gentamycin-induced hepatotoxicity. These data show that AMSCs could be a feasible therapy option for liver and kidney disease.
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Affiliation(s)
- Mohamed A Rawash
- Biotechnology Department, Faculty of biotechnology, October University for Modern Sciences and Arts (MSA) . Egypt
| | - Ayman Saber Mohamed
- Zoology Department, Faculty of Science, Cairo University, 12613, Giza. Egypt
| | - Emad M El-Zayat
- Zoology Department, Faculty of Sciences, Cairo University. Egypt
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22
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Wang M, Zhou T, Zhang Z, Liu H, Zheng Z, Xie H. Current therapeutic strategies for respiratory diseases using mesenchymal stem cells. MedComm (Beijing) 2021; 2:351-380. [PMID: 34766151 PMCID: PMC8554668 DOI: 10.1002/mco2.74] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 03/15/2021] [Accepted: 03/18/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stromal/stem cells (MSCs) have a great potential to proliferate, undergo multi-directional differentiation, and exert immunoregulatory effects. There is already much enthusiasm for their therapeutic potentials for respiratory inflammatory diseases. Although the mechanism of MSCs-based therapy has been well explored, only a few articles have summarized the key advances in this field. We hereby provide a review over the latest progresses made on the MSCs-based therapies for four types of inflammatory respiratory diseases, including idiopathic pulmonary fibrosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and asthma, and the uncovery of their underlying mechanisms from the perspective of biological characteristics and functions. Furthermore, we have also discussed the advantages and disadvantages of the MSCs-based therapies and prospects for their optimization.
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Affiliation(s)
- Ming‐yao Wang
- Laboratory of Stem Cell and Tissue EngineeringOrthopedic Research InstituteMed‐X Center for MaterialsState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
| | - Ting‐yue Zhou
- Laboratory of Stem Cell and Tissue EngineeringOrthopedic Research InstituteMed‐X Center for MaterialsState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
| | - Zhi‐dong Zhang
- Laboratory of Stem Cell and Tissue EngineeringOrthopedic Research InstituteMed‐X Center for MaterialsState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
| | - Hao‐yang Liu
- Laboratory of Stem Cell and Tissue EngineeringOrthopedic Research InstituteMed‐X Center for MaterialsState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
| | - Zhi‐yao Zheng
- Laboratory of Stem Cell and Tissue EngineeringOrthopedic Research InstituteMed‐X Center for MaterialsState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
| | - Hui‐qi Xie
- Laboratory of Stem Cell and Tissue EngineeringOrthopedic Research InstituteMed‐X Center for MaterialsState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
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23
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Chen CXQ, Abdian N, Maussion G, Thomas RA, Demirova I, Cai E, Tabatabaei M, Beitel LK, Karamchandani J, Fon EA, Durcan TM. A Multistep Workflow to Evaluate Newly Generated iPSCs and Their Ability to Generate Different Cell Types. Methods Protoc 2021; 4:mps4030050. [PMID: 34287353 PMCID: PMC8293472 DOI: 10.3390/mps4030050] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 07/10/2021] [Accepted: 07/13/2021] [Indexed: 02/07/2023] Open
Abstract
Induced pluripotent stem cells (iPSCs) derived from human somatic cells have created new opportunities to generate disease-relevant cells. Thus, as the use of patient-derived stem cells has become more widespread, having a workflow to monitor each line is critical. This ensures iPSCs pass a suite of quality-control measures, promoting reproducibility across experiments and between labs. With this in mind, we established a multistep workflow to assess our newly generated iPSCs. Our workflow tests four benchmarks: cell growth, genomic stability, pluripotency, and the ability to form the three germline layers. We also outline a simple test for assessing cell growth and highlight the need to compare different growth media. Genomic integrity in the human iPSCs is analyzed by G-band karyotyping and a qPCR-based test for the detection of common karyotypic abnormalities. Finally, we confirm that the iPSC lines can differentiate into a given cell type, using a trilineage assay, and later confirm that each iPSC can be differentiated into one cell type of interest, with a focus on the generation of cortical neurons. Taken together, we present a multistep quality-control workflow to evaluate newly generated iPSCs and detail the findings on these lines as they are tested within the workflow.
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Affiliation(s)
- Carol X.-Q. Chen
- The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (C.X.-Q.C.); (N.A.); (G.M.); (R.A.T.); (I.D.); (E.C.); (L.K.B.); (E.A.F.)
| | - Narges Abdian
- The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (C.X.-Q.C.); (N.A.); (G.M.); (R.A.T.); (I.D.); (E.C.); (L.K.B.); (E.A.F.)
| | - Gilles Maussion
- The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (C.X.-Q.C.); (N.A.); (G.M.); (R.A.T.); (I.D.); (E.C.); (L.K.B.); (E.A.F.)
| | - Rhalena A. Thomas
- The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (C.X.-Q.C.); (N.A.); (G.M.); (R.A.T.); (I.D.); (E.C.); (L.K.B.); (E.A.F.)
| | - Iveta Demirova
- The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (C.X.-Q.C.); (N.A.); (G.M.); (R.A.T.); (I.D.); (E.C.); (L.K.B.); (E.A.F.)
| | - Eddie Cai
- The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (C.X.-Q.C.); (N.A.); (G.M.); (R.A.T.); (I.D.); (E.C.); (L.K.B.); (E.A.F.)
| | - Mahdieh Tabatabaei
- The Neuro’s Clinical Biological Imaging and Genetic Repository (C-BIG), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (M.T.); (J.K.)
| | - Lenore K. Beitel
- The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (C.X.-Q.C.); (N.A.); (G.M.); (R.A.T.); (I.D.); (E.C.); (L.K.B.); (E.A.F.)
| | - Jason Karamchandani
- The Neuro’s Clinical Biological Imaging and Genetic Repository (C-BIG), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (M.T.); (J.K.)
| | - Edward A. Fon
- The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (C.X.-Q.C.); (N.A.); (G.M.); (R.A.T.); (I.D.); (E.C.); (L.K.B.); (E.A.F.)
| | - Thomas M. Durcan
- The Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada; (C.X.-Q.C.); (N.A.); (G.M.); (R.A.T.); (I.D.); (E.C.); (L.K.B.); (E.A.F.)
- Correspondence: ; Tel.: +1-514-398-6933
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Khattab MS, AbuBakr HO, El Iraqi KG, AbdElKader NA, Kamel MM, Salem KH, Steitz J, Afify M. Intra-iliac bone marrow injection as a novel alternative to intra-tibial inoculation in rat model. Stem Cell Res Ther 2021; 12:336. [PMID: 34112243 PMCID: PMC8194056 DOI: 10.1186/s13287-021-02413-7] [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: 03/01/2021] [Accepted: 05/24/2021] [Indexed: 11/10/2022] Open
Abstract
Background Intra-bone marrow injection (IBMI) in rats is adopted in many studies for stem cell and hematopoietic cell transplantation. IBMI in the tibia or the femur results in severe distress to the animal. Therefore, this study aims to evaluate intra-iliac injections as an alternative approach for IBMI. Methods Twenty-seven Sprague Dawley rats were assigned into 3 groups, 9 rats each, for 4 weeks. The control group rats were not injected. Tibia group rats were injected intra-tibial and the iliac group rats were injected intra-iliac with saline. Behavioral, radiological, histopathological, and stress evaluation was performed. Total bilirubin, cortisol, and insulin-like growth factor-1 (IGF1) were measured. Results Behavioral measurements revealed deviation compared to control, in both injected groups, on the 1st and 2nd week. By the 3rd week, it was equivalent to control in the iliac group only. Bilirubin and cortisol levels were increased by intra-tibial injection compared to intra-iliac injection. The IGF-1 gene expression increased compared to control at 1st and 2nd weeks in intra-iliac injection and decreased by intra-tibial injection at 2nd week. The thickness of the iliac crest was not different from the control group, whereas there were significant differences between the control and tibia groups. Healing of the iliac crest was faster compared to the tibia. In the 3rd week, the tibia showed fibrosis at the site of injection whereas the iliac crest showed complete bone reconstruction. Conclusion Intra-iliac injections exert less distress on animals, and by 3 weeks, they regained their normal activity in comparison to intra-tibial injections.
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Affiliation(s)
- Marwa S Khattab
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Huda O AbuBakr
- Department of Biochemistry and Molecular Biology, Cairo University, Giza, Egypt
| | - Kassem G El Iraqi
- Department of Veterinary Hygiene and Management, Cairo University, Giza, Egypt
| | - Naglaa A AbdElKader
- Department of Surgery, Anesthesiology & Radiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Mervat M Kamel
- Department of Veterinary Hygiene and Management, Cairo University, Giza, Egypt
| | - Khaled Hamed Salem
- Department of Orthopedic Surgery, Faculty of Medicine, Cairo University, Giza, Egypt.,Department of Orthopedic Surgery, RWTH Aachen University Faculty of Medicine, Aachen, Germany
| | - Julia Steitz
- Institute for Laboratory Animal Science, RWTH Aachen University Faculty of Medicine, Aachen, Germany
| | - Mamdouh Afify
- Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
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25
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Stem Cell Therapy, Ophthalmic Applications, and the Current Controversies With Direct-to-Consumer Marketing. Int Ophthalmol Clin 2021; 60:179-192. [PMID: 33093325 DOI: 10.1097/iio.0000000000000329] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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26
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Choi J, Hwang J, Kim J, Choi H. Recent Progress in Magnetically Actuated Microrobots for Targeted Delivery of Therapeutic Agents. Adv Healthc Mater 2021; 10:e2001596. [PMID: 33331143 DOI: 10.1002/adhm.202001596] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 11/13/2020] [Indexed: 12/17/2022]
Abstract
Therapeutic agents, such as drugs and cells, play an essential role in virtually every treatment of injury, illness, or disease. However, the conventional practices of drug delivery often result in undesirable side effects caused by drug overdose and off-target delivery. In the case of cell delivery, the survival rate of the transplanted cells is extremely low and difficulties with the administration route of cells remain a problem. Recently, magnetically actuated microrobots have started offering unique opportunities in targeted therapeutic delivery due to their tiny size and ability to access hard-to-reach lesions in a minimally invasive manner; considerable advances in this regard have been made over the past decade. Here, recent progress in magnetically actuated microrobots, developed for targeted drug/cell delivery, is presented, with a focus on their design features and mechanisms for controlled therapeutic release. Additionally, the practical challenges faced by the microrobots, and future research directions toward the swift bench-to-bedside translation of the microrobots are addressed.
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Affiliation(s)
- Junhee Choi
- Department of Robotics Engineering Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
- DGIST‐ETH Microrobotics Research Center Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
| | - Junsun Hwang
- Department of Robotics Engineering Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
- DGIST‐ETH Microrobotics Research Center Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
| | - Jin‐young Kim
- Department of Robotics Engineering Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
- DGIST‐ETH Microrobotics Research Center Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
| | - Hongsoo Choi
- Department of Robotics Engineering Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
- DGIST‐ETH Microrobotics Research Center Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
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27
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Andjelkov K, Conde-Green A, Mosahebi A. Smoking and Physical Activity Significantly Influence Stromal Vascular Fraction Cell Yield and Viability. Aesthetic Plast Surg 2021; 45:315-321. [PMID: 33083844 DOI: 10.1007/s00266-020-02008-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 10/04/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Subcutaneous tissue is an abundant source of adipose-derived regenerative cells. It is readily available and easy to extract by means of liposuction, making it one of the most popular sources for tissue engineering and regenerative medical applications. METHODS The stromal vascular fraction (SVF) cell yield and viability of the lipoaspirate obtained from 43 patients undergoing elective liposuction were examined in correlation with their age, gender, body mass index, smoking status, and physical activity. The lipoaspirate was processed with the Celution® 800/CRS system to isolate the SVF and a few drops of the obtained pellet were used for cell counting with NecleoCounter® NC-100TM. RESULTS Twenty-eight (65.1%) were men and 15 (34.9%) were women with an average age of 40.7 ± 10.4 years (women) and 38.9 ± 11.8 years (men). Viable SVF cells/g fat was significantly correlated with smoking level (negative correlation, ρ= - 0.312, P < 0.05) and with marginal significance with female gender. Cell viability showed a significant negative correlation with physical activity level (ρ = - 0.432, P < 0.01); borderline significance for correlation of this parameter with smoking level should not be neglected. Other parameters did not influence the cell yield nor the viability of the stromal vascular fraction. CONCLUSION Many factors may influence SVF cell yield and viability. Our findings indicate that age and smoking significantly influenced SVF cell yield, age positively while smoking negatively. Increased physical activity had a negative correlation with SVF cell viability. LEVEL OF EVIDENCE N/A This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Affiliation(s)
- Katarina Andjelkov
- Faculty of Medicine, University of Belgrade, BelPrime Clinic, 16 Brane Crncevica, 11000, Belgrade, Serbia.
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28
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Berbéri A, Sabbagh J, Bou Assaf R, Ghassibe-Sabbagh M, Al-Nemer F, El Majzoub R, Fayyad-Kazan M, Badran B. Comparing the osteogenic potential of schneiderian membrane and dental pulp mesenchymal stem cells: an in vitro study. Cell Tissue Bank 2021; 22:409-417. [PMID: 33386464 DOI: 10.1007/s10561-020-09887-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 12/04/2020] [Indexed: 10/22/2022]
Abstract
Mesenchymal stem cells, being characterized by high self-renewal capacity and multi-lineage differentiation potential, are widely used in regenerative medicine especially for repair of bone defects in patients with poor bone regenerative capacity. In this study, we aimed to compare the osteogenic potential of human maxillary schneiderian sinus membrane (hMSSM)-derived stem cells versus permanent teeth dental pulp stem cells (DPSCs). Both cells types were cultivated in osteogenic and non-osteogenic inductive media. Alkaline phosphatase (ALP) activity assay and quantitative real-time PCR analysis were carried out to assess osteogenic differentiation. We showed that ALP activity and osteoblastic markers transcription levels were more striking in hMSSM-derived stem cells than DPSCs. Our results highlight hMSSM-derived stem cells as a recommended stem cell type for usage during bone tissue regenerative therapy.
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Affiliation(s)
- Antoine Berbéri
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Lebanese University, Rafic Hariri Campus, POBox 5208-116, Beirut, Lebanon.
| | - Joseph Sabbagh
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, Lebanese University, Beirut, Lebanon
| | - Rita Bou Assaf
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Lebanese University, Rafic Hariri Campus, POBox 5208-116, Beirut, Lebanon
| | - Michella Ghassibe-Sabbagh
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
| | - Fatima Al-Nemer
- Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon
| | - Rania El Majzoub
- School of Pharmacy (Department of Biomedical Sciences), Lebanese International University, Mazraa, 146404, Lebanon
| | - Mohammad Fayyad-Kazan
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon. .,Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon.
| | - Bassam Badran
- Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences-I, Lebanese University, Hadath, Beirut, Lebanon
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Wang J, Xing H, Qin X, Ren Q, Yang J, Li L. Pharmacological effects and mechanisms of muscone. JOURNAL OF ETHNOPHARMACOLOGY 2020; 262:113120. [PMID: 32668321 DOI: 10.1016/j.jep.2020.113120] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 05/27/2020] [Accepted: 06/17/2020] [Indexed: 06/11/2023]
Abstract
Musk, the dried secretion from the preputial follicles of the male musk deer (genus Moschus), possesses various pharmacological activities and has been used extensively in traditional Chinese medicine for thousands of years. Muscone is the main active ingredient of musk and exerts pharmacological effects similar to those of musk. Although muscone was notably used to treat various disorders and diseases, such as neurological disorders, chronic inflammation and ischemia-reperfusion injury, most of the mechanisms of the pharmacological action of muscone remain unclear because of slow progress in research before the 21st century. In recent years, the pharmacological activities and mechanisms of muscone have been clarified. The present article summarizes the pharmacological and biological studies on cerebrovascular disease, cardiovascular disease, neurological effects, cancer and others and the associated mechanisms of the action of muscone to date.
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Affiliation(s)
- Jun Wang
- Health Management Center, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People's Republic of China
| | - Hui Xing
- Department of Obstetrics and Gynaecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People's Republic of China
| | - Xiaomin Qin
- Department of Obstetrics and Gynaecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People's Republic of China
| | - Qun Ren
- Health Management Center, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People's Republic of China
| | - Jiang Yang
- Department of Obstetrics and Gynaecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People's Republic of China; Department of Obstetrics and Gynaecology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
| | - Lin Li
- Department of Obstetrics and Gynaecology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People's Republic of China.
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The Impact of Advanced Glycation End-Products (AGEs) on Proliferation and Apoptosis of Primary Stem Cells: A Systematic Review. Stem Cells Int 2020; 2020:8886612. [PMID: 33281904 PMCID: PMC7685833 DOI: 10.1155/2020/8886612] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 10/27/2020] [Accepted: 10/28/2020] [Indexed: 02/06/2023] Open
Abstract
Stem cell-based regenerative therapies hold great promises to treat a wide spectrum of diseases. However, stem cell engraftment and survival are still challenging due to an unfavorable transplantation environment. Advanced glycation end-products (AGEs) can contribute to the generation of these harmful conditions. AGEs are a heterogeneous group of glycated products, nonenzymatically formed when proteins and/or lipids become glycated and oxidized. Our typical Western diet as well as cigarettes contain high AGEs content. AGEs are also endogenously formed in our body and accumulate with senescence and in pathological situations. Whether AGEs have an impact on stem cell viability in regenerative medicine remains unclear, and research on the effect of AGEs on stem cell proliferation and apoptosis is still ongoing. Therefore, this systematic review provides a clear overview of the effects of glycated proteins on cell viability in various types of primary isolated stem cells used in regenerative medicine.
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31
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Jung YD, Park SK, Kang D, Hwang S, Kang MH, Hong SW, Moon JH, Shin JS, Jin DH, You D, Lee JY, Park YY, Hwang JJ, Kim CS, Suh N. Epigenetic regulation of miR-29a/miR-30c/DNMT3A axis controls SOD2 and mitochondrial oxidative stress in human mesenchymal stem cells. Redox Biol 2020; 37:101716. [PMID: 32961441 PMCID: PMC7509080 DOI: 10.1016/j.redox.2020.101716] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/19/2020] [Accepted: 09/07/2020] [Indexed: 02/06/2023] Open
Abstract
The use of human mesenchymal stem cells (hMSCs) in clinical applications requires large-scale cell expansion prior to administration. However, the prolonged culture of hMSCs results in cellular senescence, impairing their proliferation and therapeutic potentials. To understand the role of microRNAs (miRNAs) in regulating cellular senescence in hMSCs, we globally depleted miRNAs by silencing the DiGeorge syndrome critical region 8 (DGCR8) gene, an essential component of miRNA biogenesis. DGCR8 knockdown hMSCs exhibited severe proliferation defects and senescence-associated alterations, including increased levels of reactive oxygen species (ROS). Transcriptomic analysis revealed that the antioxidant gene superoxide dismutase 2 (SOD2) was significantly downregulated in DGCR8 knockdown hMSCs. Moreover, we found that DGCR8 silencing in hMSCs resulted in hypermethylation in CpG islands upstream of SOD2. 5-aza-2'-deoxycytidine treatment restored SOD2 expression and ROS levels. We also found that these effects were dependent on the epigenetic regulator DNA methyltransferase 3 alpha (DNMT3A). Using computational and experimental approaches, we demonstrated that DNMT3A expression was regulated by miR-29a-3p and miR-30c-5p. Overexpression of miR-29a-3p and/or miR-30c-5p reduced ROS levels in DGCR8 knockdown hMSCs and rescued proliferation defects, mitochondrial dysfunction, and premature senescence. Our findings provide novel insights into hMSCs senescence regulation by the miR-29a-3p/miR-30c-5p/DNMT3A/SOD2 axis.
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Affiliation(s)
- Yi-Deun Jung
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea; Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea
| | - Seul-Ki Park
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea; Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea; Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon, 34113, Republic of Korea
| | - Dayeon Kang
- Department of Pharmaceutical Engineering, College of Medical Sciences, Soon Chun Hyang University, Asan, 31538, Republic of Korea
| | - Supyong Hwang
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Myoung-Hee Kang
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Seung-Woo Hong
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Jai-Hee Moon
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Jae-Sik Shin
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Dong-Hoon Jin
- Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Dalsan You
- Department of Urology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Joo-Yong Lee
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Yun-Yong Park
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Jung Jin Hwang
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Choung Soo Kim
- Department of Urology, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Nayoung Suh
- Department of Pharmaceutical Engineering, College of Medical Sciences, Soon Chun Hyang University, Asan, 31538, Republic of Korea.
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Srivastava RK, Singh P. Stem cell therapies as a therapeutic option to counter chemo brain: a negative effect of cancer treatment. Regen Med 2020; 15:1789-1800. [PMID: 32844724 DOI: 10.2217/rme-2020-0060] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Chemo brain, a constellation of cognitive deficiencies followed by chemotherapy drugs, used to treat different types of cancers and adversely impacts the quality of life of a cancer survivor. The underlying mechanism of chemo brain remains vague, thus delaying the advancement of efficient treatments. Unfortunately, there is no US FDA approved medicine for chemo brain and often medicines considered for chemo brain are already the ones approved for other diseases. Nevertheless, researches exploring stem cell transplantation in different neurodegenerative diseases demonstrate that cellular transplantation could reverse chemotherapy-induced chemo brain. This review talks about the mechanism behind the cognitive impairments instigated by different chemotherapy drugs used in cancer treatment, and how stem cell therapy could be advantageous to overcome this disease.
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Affiliation(s)
- Rohit K Srivastava
- Department of Pediatrics Surgery, Texas Children's Hospital, Houston, TX 77030, USA.,M.E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
| | - Pratibha Singh
- Department of Biochemistry and Cell Biology, Biosciences Research Collaborative, Rice University, Houston, TX 77030, USA
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Tutuianu R, Rosca AM, Albu Kaya MG, Pruna V, Neagu TP, Lascar I, Simionescu M, Titorencu I. Mesenchymal stromal cell-derived factors promote the colonization of collagen 3D scaffolds with human skin cells. J Cell Mol Med 2020; 24:9692-9704. [PMID: 32666712 PMCID: PMC7520263 DOI: 10.1111/jcmm.15507] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 05/07/2020] [Accepted: 05/31/2020] [Indexed: 12/12/2022] Open
Abstract
The development of stem cell technology in combination with advances in biomaterials has opened new ways of producing engineered tissue substitutes. In this study, we investigated whether the therapeutic potential of an acellular porous scaffold made of type I collagen can be improved by the addition of a powerful trophic agent in the form of mesenchymal stromal cells conditioned medium (MSC-CM) in order to be used as an acellular scaffold for skin wound healing treatment. Our experiments showed that MSC-CM sustained the adherence of keratinocytes and fibroblasts as well as the proliferation of keratinocytes. Moreover, MSC-CM had chemoattractant properties for keratinocytes and endothelial cells, attributable to the content of trophic and pro-angiogenic factors. Also, for the dermal fibroblasts cultured on collagen scaffold in the presence of MSC-CM versus serum control, the ratio between collagen III and I mRNAs increased by 2-fold. Furthermore, the gene expression for α-smooth muscle actin, tissue inhibitor of metalloproteinase-1 and 2 and matrix metalloproteinase-14 was significantly increased by approximately 2-fold. In conclusion, factors existing in MSC-CM improve the colonization of collagen 3D scaffolds, by sustaining the adherence and proliferation of keratinocytes and by inducing a pro-healing phenotype in fibroblasts.
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Affiliation(s)
- Raluca Tutuianu
- Institute of Cellular Biology and Pathology, "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania
| | - Ana-Maria Rosca
- Institute of Cellular Biology and Pathology, "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania
| | | | - Vasile Pruna
- INCDTP-Division Leather and Footwear Research Institute, Bucharest, Romania
| | | | - Ioan Lascar
- University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania
| | - Maya Simionescu
- Institute of Cellular Biology and Pathology, "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania
| | - Irina Titorencu
- Institute of Cellular Biology and Pathology, "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania
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Abstract
Head and neck structures govern the vital functions of breathing and swallowing. Additionally, these structures facilitate our sense of self through vocal communication, hearing, facial animation, and physical appearance. Loss of these functions can lead to loss of life or greatly affect quality of life. Regenerative medicine is a rapidly developing field that aims to repair or replace damaged cells, tissues, and organs. Although the field is largely in its nascence, regenerative medicine holds promise for improving on conventional treatments for head and neck disorders or providing therapies where no current standard exists. This review presents milestones in the research of regenerative medicine in head and neck surgery.
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Affiliation(s)
- Michael J McPhail
- Head and Neck Regenerative Medicine Laboratory, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Jeffrey R Janus
- Department of Otolaryngology - Head and Neck Surgery, Mayo Clinic Florida, Jacksonville, FL, USA
| | - David G Lott
- Head and Neck Regenerative Medicine Laboratory, Mayo Clinic Arizona, Scottsdale, AZ, USA
- Department of Otolaryngology - Head and Neck Surgery, Mayo Clinic Arizona, Phoenix, AZ, USA
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35
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Prina E, Amer MH, Sidney L, Tromayer M, Moore J, Liska R, Bertolin M, Ferrari S, Hopkinson A, Dua H, Yang J, Wildman R, Rose FRAJ. Bioinspired Precision Engineering of Three-Dimensional Epithelial Stem Cell Microniches. ACTA ACUST UNITED AC 2020; 4:e2000016. [PMID: 32329968 DOI: 10.1002/adbi.202000016] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 03/22/2020] [Accepted: 03/31/2020] [Indexed: 12/16/2022]
Abstract
Maintenance of the epithelium relies on stem cells residing within specialized microenvironments, known as epithelial crypts. Two-photon polymerization (2PP) is a valuable tool for fabricating 3D micro/nanostructures for stem cell niche engineering applications. Herein, biomimetic gelatin methacrylate-based constructs, replicating the precise geometry of the limbal epithelial crypt structures (limbal stem cell "microniches") as an exemplar epithelial niche, are fabricated using 2PP. Human limbal epithelial stem cells (hLESCs) are seeded within the microniches in xeno-free conditions to investigate their ability to repopulate the crypts and the expression of various differentiation markers. Cell proliferation and a zonation in cell phenotype along the z-axis are observed without the use of exogenous signaling molecules. Significant differences in cell phenotype between cells located at the base of the microniche and those situated towards the rim are observed, demonstrating that stem cell fate is strongly influenced by its location within a niche and the geometrical details of where it resides. This study provides insight into the influence of the niche's spatial geometry on hLESCs and demonstrates a flexible approach for the fabrication of biomimetic crypt-like structures in epithelial tissues. This has significant implications for regenerative medicine applications and can ultimately lead to implantable synthetic "niche-based" treatments.
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Affiliation(s)
- Elisabetta Prina
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, Nottingham Biodiscovery Institute, University of Nottingham, Nottingham, NG7 2RD, UK
| | - Mahetab H Amer
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, Nottingham Biodiscovery Institute, University of Nottingham, Nottingham, NG7 2RD, UK
| | - Laura Sidney
- Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK
| | - Maximilian Tromayer
- Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163, Vienna, 1060, Austria
| | - Jonathan Moore
- School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK
| | - Robert Liska
- Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163, Vienna, 1060, Austria
| | - Marina Bertolin
- Fondazione Banca degli Occhi del Veneto Onlus, Padiglione Rama, Via Paccagnella 11, Zelarino-Venezia, 30174, Italy
| | - Stefano Ferrari
- Fondazione Banca degli Occhi del Veneto Onlus, Padiglione Rama, Via Paccagnella 11, Zelarino-Venezia, 30174, Italy
| | - Andrew Hopkinson
- Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK
| | - Harminder Dua
- Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, NG7 2UH, UK
| | - Jing Yang
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, Nottingham Biodiscovery Institute, University of Nottingham, Nottingham, NG7 2RD, UK
| | - Ricky Wildman
- Institute of Advanced Manufacturing, Faculty of Engineering, University of Nottingham, Nottingham, NG7 2RD, UK
| | - Felicity R A J Rose
- Division of Regenerative Medicine and Cellular Therapies, School of Pharmacy, Nottingham Biodiscovery Institute, University of Nottingham, Nottingham, NG7 2RD, UK
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Feng L, Liang S, Zhou Y, Luo Y, Chen R, Huang Y, Chen Y, Xu M, Yao R. Three-Dimensional Printing of Hydrogel Scaffolds with Hierarchical Structure for Scalable Stem Cell Culture. ACS Biomater Sci Eng 2020; 6:2995-3004. [DOI: 10.1021/acsbiomaterials.9b01825] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Lu Feng
- Key Laboratory for Advanced Materials Processing Technology of Ministry of Education, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
| | - Shaojun Liang
- Key Laboratory for Advanced Materials Processing Technology of Ministry of Education, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
| | - Yongyong Zhou
- Key Laboratory of Medical Information and 3D Bioprinting of Zhejiang Province, Hangzhou Dianzi University, Hangzhou 310018, China
| | - Yixue Luo
- Key Laboratory for Advanced Materials Processing Technology of Ministry of Education, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
| | - Ruoyu Chen
- Key Laboratory for Advanced Materials Processing Technology of Ministry of Education, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
| | - Yuyu Huang
- Key Laboratory for Advanced Materials Processing Technology of Ministry of Education, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
| | - Yiqing Chen
- Key Laboratory for Advanced Materials Processing Technology of Ministry of Education, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
| | - Mingen Xu
- Key Laboratory of Medical Information and 3D Bioprinting of Zhejiang Province, Hangzhou Dianzi University, Hangzhou 310018, China
| | - Rui Yao
- Key Laboratory for Advanced Materials Processing Technology of Ministry of Education, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
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Kautz R, Phan L, Arulmoli J, Chatterjee A, Kerr JP, Naeim M, Long J, Allevato A, Leal-Cruz JE, Le L, Derakhshan P, Tombola F, Flanagan LA, Gorodetsky AA. Growth and Spatial Control of Murine Neural Stem Cells on Reflectin Films. ACS Biomater Sci Eng 2020; 6:1311-1320. [PMID: 33455403 PMCID: PMC7833438 DOI: 10.1021/acsbiomaterials.9b00824] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 12/19/2019] [Indexed: 02/06/2023]
Abstract
Stem cells have attracted significant attention due to their regenerative capabilities and their potential for the treatment of disease. Consequently, significant research effort has focused on the development of protein- and polypeptide-based materials as stem cell substrates and scaffolds. Here, we explore the ability of reflectin, a cephalopod structural protein, to support the growth of murine neural stem/progenitor cells (mNSPCs). We observe that the binding, growth, and differentiation of mNSPCs on reflectin films is comparable to that on more established protein-based materials. Moreover, we find that heparin selectively inhibits the adhesion of mNSPCs on reflectin, affording spatial control of cell growth and leading to a >30-fold change in cell density on patterned substrates. The described findings highlight the potential utility of reflectin as a stem cell culture material.
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Affiliation(s)
- Rylan Kautz
- Department
of Chemical Engineering and Materials Science, University of California, Irvine, 916 Engineering Tower, Irvine, California 92697, United States
| | - Long Phan
- Department
of Chemical Engineering and Materials Science, University of California, Irvine, 916 Engineering Tower, Irvine, California 92697, United States
| | - Janahan Arulmoli
- Department
of Biomedical Engineering, University of
California, Irvine, 3120
Natural Sciences II, Irvine, California 92697, United States
- Sue
and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, California 92697, United States
| | - Atrouli Chatterjee
- Department
of Chemical Engineering and Materials Science, University of California, Irvine, 916 Engineering Tower, Irvine, California 92697, United States
| | - Justin P. Kerr
- Department
of Mechanical and Aerospace Engineering, University of California, Irvine, 4200 Engineering Gateway Building, Irvine, California 92697, United States
| | - Mahan Naeim
- Department
of Biomedical Engineering, University of
California, Irvine, 3120
Natural Sciences II, Irvine, California 92697, United States
| | - James Long
- Department
of Chemical Engineering and Materials Science, University of California, Irvine, 916 Engineering Tower, Irvine, California 92697, United States
| | - Alex Allevato
- Department
of Chemical Engineering and Materials Science, University of California, Irvine, 916 Engineering Tower, Irvine, California 92697, United States
| | - Jessica E. Leal-Cruz
- Department
of Chemical Engineering and Materials Science, University of California, Irvine, 916 Engineering Tower, Irvine, California 92697, United States
| | - LeAnn Le
- Department
of Chemical Engineering and Materials Science, University of California, Irvine, 916 Engineering Tower, Irvine, California 92697, United States
| | - Parsa Derakhshan
- Department
of Chemical Engineering and Materials Science, University of California, Irvine, 916 Engineering Tower, Irvine, California 92697, United States
| | - Francesco Tombola
- Department
of Physiology and Biophysics, University
of California, Irvine, 825 Health Sciences Road, Irvine, California 92697, United States
| | - Lisa A. Flanagan
- Department
of Biomedical Engineering, University of
California, Irvine, 3120
Natural Sciences II, Irvine, California 92697, United States
- Sue
and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, California 92697, United States
- Department
of Neurology, University of California,
Irvine, 200 South Manchester
Avenue, Orange, California 92868, United States
| | - Alon A. Gorodetsky
- Department
of Chemical Engineering and Materials Science, University of California, Irvine, 916 Engineering Tower, Irvine, California 92697, United States
- Department
of Chemistry, University of California,
Irvine, 1102 Natural
Sciences II, Irvine, California 92697, United States
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Lights and Shadows in the Use of Mesenchymal Stem Cells in Lung Inflammation, a Poorly Investigated Topic in Cystic Fibrosis. Cells 2019; 9:cells9010020. [PMID: 31861724 PMCID: PMC7016730 DOI: 10.3390/cells9010020] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 12/12/2019] [Accepted: 12/17/2019] [Indexed: 12/14/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic stem cells residing in many tissues, including the lung. MSCs have long been regarded as a promising tool for cell-based therapy because of their ability to replace damaged tissue by differentiating into the resident cell and repopulating the injured area. Their ability to release soluble factors and extracellular vesicles has emerged as crucial in the resolution of inflammation and injury. There is a growing literature on the use of MSCs and MSC secretome to hamper inflammation in different lung pathologies, including: asthma, pneumonia, acute lung injury (ALI), pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). However, their potential therapeutic role in the context of Cystic Fibrosis (CF) lung inflammation is still not fully characterized. CF morbidity and mortality are mainly due to progressive lung dysfunction. Lung inflammation is a chronic and unresolved condition that triggers progressive tissue damage. Thus, it becomes even more important to develop innovative immunomodulatory therapies aside from classic anti-inflammatory agents. Here, we address the main features of CF and the implications in lung inflammation. We then review how MSCs and MSC secretome participate in attenuating inflammation in pulmonary pathologies, emphasizing the significant potential of MSCs as new therapeutic approach in CF.
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Guan S, Zhang K, Li J. Recent Advances in Extracellular Matrix for Engineering Stem Cell Responses. Curr Med Chem 2019; 26:6321-6338. [DOI: 10.2174/0929867326666190704121309] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 12/02/2018] [Accepted: 01/25/2019] [Indexed: 02/06/2023]
Abstract
Stem cell transplantation is an advanced medical technology, which brings hope for the
treatment of some difficult diseases in the clinic. Attributed to its self-renewal and differential
ability, stem cell research has been pushed to the forefront of regenerative medicine and has become
a hot topic in tissue engineering. The surrounding extracellular matrix has physical functions
and important biological significance in regulating the life activities of cells, which may play crucial
roles for in situ inducing specific differentiation of stem cells. In this review, we discuss the
stem cells and their engineering application, and highlight the control of the fate of stem cells, we
offer our perspectives on the various challenges and opportunities facing the use of the components
of extracellular matrix for stem cell attachment, growth, proliferation, migration and differentiation.
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Affiliation(s)
- Shuaimeng Guan
- School of Life Science, Zhengzhou University, Zhengzhou 450000, China
| | - Kun Zhang
- School of Life Science, Zhengzhou University, Zhengzhou 450000, China
| | - Jingan Li
- School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450000, China
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Bahsoun S, Coopman K, Akam EC. The impact of cryopreservation on bone marrow-derived mesenchymal stem cells: a systematic review. J Transl Med 2019; 17:397. [PMID: 31783866 PMCID: PMC6883667 DOI: 10.1186/s12967-019-02136-7] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Accepted: 11/12/2019] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells (MSCs) represent an invaluable asset for the field of cell therapy. Human Bone marrow-derived MSCs (hBM-MSCs) are one of the most commonly used cell types in clinical trials. They are currently being studied and tested for the treatment of a wide range of diseases and conditions. The future availability of MSCs therapies to the public will require a robust and reliable delivery process. Cryopreservation represents the gold standard in cell storage and transportation, but its effect on BM-MSCs is still not well established. A systematic review was conducted to evaluate the impact of cryopreservation on BM-MSCs and to attempt to uncover the reasons behind some of the controversial results reported in the literature. Forty-one in vitro studies were analysed, and their results organised according to the cell attributes they assess. It was concluded that cryopreservation does not affect BM-MSCs morphology, surface marker expression, differentiation or proliferation potential. However, mixed results exist regarding the effect on colony forming ability and the effects on viability, attachment and migration, genomic stability and paracrine function are undefined mainly due to the huge variabilities governing the cryopreservation process as a whole and to the lack of standardised assays.
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Affiliation(s)
- Soukaina Bahsoun
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK
| | - Karen Coopman
- Centre for Biological Engineering, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK
| | - Elizabeth C Akam
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK.
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41
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García-Sánchez D, Fernández D, Rodríguez-Rey JC, Pérez-Campo FM. Enhancing survival, engraftment, and osteogenic potential of mesenchymal stem cells. World J Stem Cells 2019; 11:748-763. [PMID: 31692976 PMCID: PMC6828596 DOI: 10.4252/wjsc.v11.i10.748] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 07/15/2019] [Accepted: 07/29/2019] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are promising candidates for bone regeneration therapies due to their plasticity and easiness of sourcing. MSC-based treatments are generally considered a safe procedure, however, the long-term results obtained up to now are far from satisfactory. The main causes of these therapeutic limitations are inefficient homing, engraftment, and osteogenic differentiation. Many studies have proposed modifications to improve MSC engraftment and osteogenic differentiation of the transplanted cells. Several strategies are aimed to improve cell resistance to the hostile microenvironment found in the recipient tissue and increase cell survival after transplantation. These strategies could range from a simple modification of the culture conditions, known as cell-preconditioning, to the genetic modification of the cells to avoid cellular senescence. Many efforts have also been done in order to enhance the osteogenic potential of the transplanted cells and induce bone formation, mainly by the use of bioactive or biomimetic scaffolds, although alternative approaches will also be discussed. This review aims to summarize several of the most recent approaches, providing an up-to-date view of the main developments in MSC-based regenerative techniques.
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Affiliation(s)
- Daniel García-Sánchez
- Department of Molecular Biology, Faculty of Medicine, University of Cantabria, Cantabria 39011, Spain
| | - Darío Fernández
- Laboratorio de Biología Celular y Molecular, Facultad de Odontología, Universidad Nacional del Nordeste, Corrientes W3400, Argentina
| | - José C Rodríguez-Rey
- Department of Molecular Biology, Faculty of Medicine, University of Cantabria, Cantabria 39011, Spain
| | - Flor M Pérez-Campo
- Department of Molecular Biology, Faculty of Medicine, University of Cantabria, Cantabria 39011, Spain.
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Li XF, Zhou YW, Cai PF, Fu WC, Wang JH, Chen JY, Yang QN. CRISPR/Cas9 facilitates genomic editing for large-scale functional studies in pluripotent stem cell cultures. Hum Genet 2019; 138:1217-1225. [PMID: 31606751 DOI: 10.1007/s00439-019-02071-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Accepted: 10/04/2019] [Indexed: 12/13/2022]
Abstract
Pluripotent stem cell (PSC) cultures form an integral part of biomedical and medical research due to their capacity to rapidly proliferate and differentiate into hundreds of highly specialized cell types. This makes them a highly useful tool in exploring human physiology and disease. Genomic editing of PSC cultures is an essential method of attaining answers to basic physiological functions, developing in vitro models of human disease, and exploring potential therapeutic strategies and the identification of drug targets. Achieving reliable and efficient genomic editing is an important aspect of using large-scale PSC cultures. The CRISPR/Cas9 genomic editing tool has facilitated highly efficient gene knockout, gene correction, or gene modifications through the design and use of single-guide RNAs which are delivered to the target DNA via Cas9. CRISPR/Cas9 modification of PSCs has furthered the understanding of basic physiology and has been utilized to develop in vitro disease models, to test therapeutic strategies, and to facilitate regenerative or tissue repair approaches. In this review, we discuss the benefits of the CRISPR/Cas9 system in large-scale PSC cultures.
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Affiliation(s)
- Xiao-Fei Li
- Department of Joint Surgery, Jinhua Municipal Central Hospital, No. 365 Renmin East Road, Wucheng District, Jinhua, 321000, Zhejiang, People's Republic of China
| | - Yong-Wei Zhou
- Department of Joint Surgery, Jinhua Municipal Central Hospital, No. 365 Renmin East Road, Wucheng District, Jinhua, 321000, Zhejiang, People's Republic of China
| | - Peng-Fei Cai
- Department of Joint Surgery, Jinhua Municipal Central Hospital, No. 365 Renmin East Road, Wucheng District, Jinhua, 321000, Zhejiang, People's Republic of China
| | - Wei-Cong Fu
- Department of Joint Surgery, Jinhua Municipal Central Hospital, No. 365 Renmin East Road, Wucheng District, Jinhua, 321000, Zhejiang, People's Republic of China
| | - Jin-Hua Wang
- Department of Joint Surgery, Jinhua Municipal Central Hospital, No. 365 Renmin East Road, Wucheng District, Jinhua, 321000, Zhejiang, People's Republic of China
| | - Jin-Yang Chen
- Research and Development Department, Zhejiang Healthfuture Institute for Cell-Based Applied Technology, Hangzhou, 310052, Zhejiang, People's Republic of China
| | - Qi-Ning Yang
- Department of Joint Surgery, Jinhua Municipal Central Hospital, No. 365 Renmin East Road, Wucheng District, Jinhua, 321000, Zhejiang, People's Republic of China.
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Chen F, Li T, Sun Y, Liu Q, Yang T, Chen J, Zhu H, Shi Y, Hu YP, Wang MJ. Generation of insulin-secreting cells from mouse gallbladder stem cells by small molecules in vitro. Stem Cell Res Ther 2019; 10:289. [PMID: 31547878 PMCID: PMC6757438 DOI: 10.1186/s13287-019-1407-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Revised: 07/29/2019] [Accepted: 09/03/2019] [Indexed: 12/11/2022] Open
Abstract
Background Stem cell-derived pancreatic β-like cells hold great promise for treating diabetes. Gallbladder belongs to the extrahepatic bile duct system and possesses stem-like cells. These stem cells could be expanded in vitro and have the potential of differentiating into hepatocytes, cholangiocytes, or pancreatic cells. As the gallbladder is highly available, gallbladder stem cells provide a new cell source of pancreatic β-like cells. In this study, we aimed to investigate an approach for the generation of pancreatic β-like cells from gallbladder stem cells (GSCs) without genetic modification. Methods A CK19CreERT;Rosa26R-GFP mouse was used to isolate CK19+ cells, which represented EpCAM+ stem cells in the gallbladder. They were cultured in the modified Kubota’s medium for expansion and further analyzed. Then, we developed a strategy to screen a combination of small molecules that can generate insulin-secreting cells from gallbladder stem cells. These cells were identified with markers of pancreatic cells. Finally, they were seeded into the cellulosic sponge and transplanted to the diabetic mice for functional examination in vivo. Results Gallbladder stem cells could be expanded for more than 15 passages. They expressed typical hepatic stem cell markers including CK19, EpCAM, Sox9, and albumin. By screening method, we found that adding Noggin, FR180204, and cyclopamine could efficiently induce gallbladder stem cells differentiating into insulin-secreting cells. These cells expressed Pdx1, Nkx6.1, and insulin but were negative for Gcg. After transplantation with the cellulosic sponge, they could ameliorate hyperglycemia in the diabetic mice. Conclusion This study provides a new approach which can generate insulin-secreting cells from the gallbladder without genetic modification. This offers an option for β cell therapy in treating type 1 diabetes.
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Affiliation(s)
- Fei Chen
- Department of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, China
| | - Tuo Li
- Department of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, China.,Department of Endocrinology, Changzheng Hospital, Navy Medical University (Second Military Medical University), 415 Fengyang Road, Shanghai, 200003, China
| | - Yu Sun
- Department of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, China
| | - Qinggui Liu
- Department of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, China
| | - Tao Yang
- Department of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, China
| | - Jiajia Chen
- Department of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, China
| | - Haiying Zhu
- Department of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, China
| | - Yongquan Shi
- Department of Endocrinology, Changzheng Hospital, Navy Medical University (Second Military Medical University), 415 Fengyang Road, Shanghai, 200003, China.
| | - Yi-Ping Hu
- Department of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, China.
| | - Min-Jun Wang
- Department of Cell Biology, Center for Stem Cell and Medicine, Navy Medical University (Second Military Medical University), 800 Xiangyin Road, Shanghai, 200433, China.
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Stem cell-based bone and dental regeneration: a view of microenvironmental modulation. Int J Oral Sci 2019; 11:23. [PMID: 31423011 PMCID: PMC6802669 DOI: 10.1038/s41368-019-0060-3] [Citation(s) in RCA: 139] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 05/28/2019] [Accepted: 06/12/2019] [Indexed: 02/06/2023] Open
Abstract
In modern medicine, bone and dental loss and defects are common and widespread morbidities, for which regenerative therapy has shown great promise. Mesenchymal stem cells, obtained from various sources and playing an essential role in organ development and postnatal repair, have exhibited enormous potential for regenerating bone and dental tissue. Currently, mesenchymal stem cells (MSCs)-based bone and dental regeneration mainly includes two strategies: the rescue or mobilization of endogenous MSCs and the application of exogenous MSCs in cytotherapy or tissue engineering. Nevertheless, the efficacy of MSC-based regeneration is not always fulfilled, especially in diseased microenvironments. Specifically, the diseased microenvironment not only impairs the regenerative potential of resident MSCs but also controls the therapeutic efficacy of exogenous MSCs, both as donors and recipients. Accordingly, approaches targeting a diseased microenvironment have been established, including improving the diseased niche to restore endogenous MSCs, enhancing MSC resistance to a diseased microenvironment and renormalizing the microenvironment to guarantee MSC-mediated therapies. Moreover, the application of extracellular vesicles (EVs) as cell-free therapy has emerged as a promising therapeutic strategy. In this review, we summarize current knowledge regarding the tactics of MSC-based bone and dental regeneration and the decisive role of the microenvironment, emphasizing the therapeutic potential of microenvironment-targeting strategies in bone and dental regenerative medicine.
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Bulun SE, Yilmaz BD, Sison C, Miyazaki K, Bernardi L, Liu S, Kohlmeier A, Yin P, Milad M, Wei J. Endometriosis. Endocr Rev 2019; 40:1048-1079. [PMID: 30994890 PMCID: PMC6693056 DOI: 10.1210/er.2018-00242] [Citation(s) in RCA: 469] [Impact Index Per Article: 78.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 04/08/2019] [Indexed: 02/08/2023]
Abstract
Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-β. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.
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Affiliation(s)
- Serdar E Bulun
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Bahar D Yilmaz
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Christia Sison
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Kaoru Miyazaki
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Lia Bernardi
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Shimeng Liu
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Amanda Kohlmeier
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Ping Yin
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Magdy Milad
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - JianJun Wei
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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Browne S, Healy KE. Matrix-assisted cell transplantation for tissue vascularization. Adv Drug Deliv Rev 2019; 146:155-169. [PMID: 30605738 DOI: 10.1016/j.addr.2018.12.016] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 10/30/2018] [Accepted: 12/27/2018] [Indexed: 12/20/2022]
Abstract
Cell therapy offers much promise for the treatment of ischemic diseases by augmenting tissue vasculogenesis. Matrix-assisted cell transplantation (MACT) has been proposed as a solution to enhance cell survival and integration with host tissue following transplantation. By designing semi synthetic matrices (sECM) with the correct physical and biochemical signals, encapsulated cells are directed towards a more angiogenic phenotype. In this review, we describe the choice of cells suitable for pro-angiogenic therapies, the properties that should be considered when designing sECM for transplantation and their relative importance. Pre-clinical models where MACT has been successfully applied to promote angiogenesis are reviewed to show the great potential of this strategy to treat ischemic conditions.
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Affiliation(s)
- Shane Browne
- Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Materials Science and Engineering, University of California, Berkeley, CA 94720, USA; Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway, Ireland
| | - Kevin E Healy
- Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Department of Materials Science and Engineering, University of California, Berkeley, CA 94720, USA.
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Cell Therapy: Past, Present, and Future. CURRENT TRANSPLANTATION REPORTS 2019. [DOI: 10.1007/s40472-019-00235-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Short-Term Protocols to Obtain Insulin-Producing Cells from Rat Adipose Tissue: Signaling Pathways and In Vivo Effect. Int J Mol Sci 2019; 20:ijms20102458. [PMID: 31109026 PMCID: PMC6566438 DOI: 10.3390/ijms20102458] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Revised: 05/09/2019] [Accepted: 05/13/2019] [Indexed: 02/06/2023] Open
Abstract
Studies using mesenchymal stromal cells (MSCs) as a source of insulin-secreting cells (IPCs) are a promising path in the pursuit for diabetes therapy. Here, we investigate three short-term differentiation protocols in order to generate IPCs from autologous adipose-derived stromal cells (ADSCs) with an expressive insulin-secreting profile in vitro and in vivo, as well as the signaling pathways involved in the chosen differentiation protocols. We extracted and cultured ADSCs and differentiated them into IPCs, using three different protocols with different inductors. Afterwards, the secretory profile was analyzed and IPCs differentiated in exendin-4/activin A medium, which presented the best secretory profile, was implanted in the kidney subcapsular region of diabetic rats. All protocols induced the differentiation, but media supplemented with exendin-4/activin A or resveratrol induced the expression and secretion of insulin more efficiently, and only the exendin-4/activin-A-supplemented medium generated an insulin secretion profile more like β-cells, in response to glucose. The PI3K/Akt pathway seems to play a negative role in IPC differentiation; however, the differentiation of ADSCs with exendin-4/activin A positively modulated the p38/MAPK pathway. Resveratrol medium activated the Jak/STAT3 pathway and generated IPCs apparently less sensitive to insulin and insulin-like receptors. Finally, the implant of IPCs with the best secretory behavior caused a decrease in hyperglycemia after one-week implantation in diabetic rats. Our data provide further information regarding the generation of IPCs from ADSCs and strengthen evidence to support the use of MSCs in regenerative medicine, specially the use of exendin-4/activin A to produce rapid and effectively IPCs with significant in vivo effects.
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From the margins to mainstream: How providers of autologous ‘stem cell treatments’ legitimise their practice in Australia. Health (London) 2019; 25:51-68. [DOI: 10.1177/1363459319846927] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
This article examines how Australian providers of unproven autologous ‘stem cell treatments’ legitimise these products and their practices. We focus on the strategies employed by providers in their efforts to create and sustain a market for procedures that have yet to be proven safe and clinically efficacious. Drawing on the work of Thomas Gieryn and Pierre Bourdieu and the findings of research involving an analysis of direct-to-consumer online advertising of clinics that sell purported ‘stem cell treatments’ and interviews with clinicians who provide them, we examine the mechanisms by which medical legitimacy for these products is established and defended. We argue that Australian providers employ a number of strategies in order to create medical legitimacy for the use and sale of scientifically unproven therapies. A key strategy employed by providers of stem cell treatments is to use markers of social distinction, drawing strongly on the symbols of science, to confirm their legitimacy and differentiate their own practices from those of other providers, who are posited as operating outside the boundary of accepted practice and hence illegitimate. We argue there is a paradox at the heart of the autologous stem cell treatment market. Providers aim to create legitimacy for their work by emphasising the potential benefits of their ‘treatments’, their expertise and the professionalisation of their practices in an environment where regulators are yet to take a firm stance; they are also required to undertake the challenging task of managing patients’ hopes and expectations that both enable and potentially jeopardise their operations and revenue. We conclude by suggesting that providers’ creation of symbolic capital to establish medical legitimacy is a crucial means by which they seek to bring unproven ‘stem cell treatments’ from the margins of medicine into the mainstream and to portray themselves as medical pioneers rather than medical cowboys who exploit vulnerable patients.
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Cell membrane engineering with synthetic materials: Applications in cell spheroids, cellular glues and microtissue formation. Acta Biomater 2019; 90:21-36. [PMID: 30986529 DOI: 10.1016/j.actbio.2019.04.013] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 03/26/2019] [Accepted: 04/03/2019] [Indexed: 12/16/2022]
Abstract
Biologically inspired materials with tunable bio- and physicochemical properties provide an essential framework to actively control and support cellular behavior. Cell membrane remodeling approaches benefit from the advances in polymer science and bioconjugation methods, which allow for the installation of un-/natural molecules and particles on the cells' surface. Synthetically remodeled cells have superior properties and are under intense investigation in various therapeutic scenarios as cell delivery systems, bio-sensing platforms, injectable biomaterials and bioinks for 3D bioprinting applications. In this review article, recent advances in the field of cell surface remodeling via bio-chemical means and the potential biomedical applications of these emerging cell hybrids are discussed. STATEMENT OF SIGNIFICANCE: Recent advances in bioconjugation methods, controlled/living polymerizations, microfabrication techniques and 3D printing technologies have enabled researchers to probe specific cellular functions and cues for therapeutic and research purposes through the formation of cell spheroids and polymer-cell chimeras. This review article highlights recent non-genetic cell membrane engineering strategies towards the fabrication of cellular ensembles and microtissues with interest in 3D in vitro modeling, cell therapeutics and tissue engineering. From a wider perspective, these approaches may provide a roadmap for future advances in cell therapies which will expedite the clinical use of cells, thereby improving the quality and accessibility of disease treatments.
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