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Osouli-Bostanabad K, Masalehdan T, Kapsa RMI, Quigley A, Lalatsa A, Bruggeman KF, Franks SJ, Williams RJ, Nisbet DR. Traction of 3D and 4D Printing in the Healthcare Industry: From Drug Delivery and Analysis to Regenerative Medicine. ACS Biomater Sci Eng 2022; 8:2764-2797. [PMID: 35696306 DOI: 10.1021/acsbiomaterials.2c00094] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Three-dimensional (3D) printing and 3D bioprinting are promising technologies for a broad range of healthcare applications from frontier regenerative medicine and tissue engineering therapies to pharmaceutical advancements yet must overcome the challenges of biocompatibility and resolution. Through comparison of traditional biofabrication methods with 3D (bio)printing, this review highlights the promise of 3D printing for the production of on-demand, personalized, and complex products that enhance the accessibility, effectiveness, and safety of drug therapies and delivery systems. In addition, this review describes the capacity of 3D bioprinting to fabricate patient-specific tissues and living cell systems (e.g., vascular networks, organs, muscles, and skeletal systems) as well as its applications in the delivery of cells and genes, microfluidics, and organ-on-chip constructs. This review summarizes how tailoring selected parameters (i.e., accurately selecting the appropriate printing method, materials, and printing parameters based on the desired application and behavior) can better facilitate the development of optimized 3D-printed products and how dynamic 4D-printed strategies (printing materials designed to change with time or stimulus) may be deployed to overcome many of the inherent limitations of conventional 3D-printed technologies. Comprehensive insights into a critical perspective of the future of 4D bioprinting, crucial requirements for 4D printing including the programmability of a material, multimaterial printing methods, and precise designs for meticulous transformations or even clinical applications are also given.
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Affiliation(s)
- Karim Osouli-Bostanabad
- Biomaterials, Bio-engineering and Nanomedicine (BioN) Lab, Institute of Biomedical and Biomolecular, Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, White Swan Road, Portsmouth PO1 2DT, United Kingdom
| | - Tahereh Masalehdan
- Department of Materials Engineering, Institute of Mechanical Engineering, University of Tabriz, Tabriz 51666-16444, Iran
| | - Robert M I Kapsa
- Biomedical and Electrical Engineering, School of Engineering, RMIT University, Melbourne, Victoria 3000, Australia.,Department of Medicine, St Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, Victoria 3065, Australia
| | - Anita Quigley
- Biomedical and Electrical Engineering, School of Engineering, RMIT University, Melbourne, Victoria 3000, Australia.,Department of Medicine, St Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, Victoria 3065, Australia
| | - Aikaterini Lalatsa
- Biomaterials, Bio-engineering and Nanomedicine (BioN) Lab, Institute of Biomedical and Biomolecular, Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, White Swan Road, Portsmouth PO1 2DT, United Kingdom
| | - Kiara F Bruggeman
- Laboratory of Advanced Biomaterials, Research School of Chemistry and the John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.,Research School of Electrical, Energy and Materials Engineering, The Australian National University, Canberra, Australian Capital Territory 2601, Australia
| | - Stephanie J Franks
- Laboratory of Advanced Biomaterials, Research School of Chemistry and the John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia
| | - Richard J Williams
- Institute of Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Waurn Ponds, Victoria 3216, Australia
| | - David R Nisbet
- Laboratory of Advanced Biomaterials, Research School of Chemistry and the John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.,The Graeme Clark Institute, The University of Melbourne, Melbourne, Victoria 3010, Australia.,Department of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Melbourne, Melbourne, Victoria 3010, Australia
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Xue M, Zhao R, March L, Jackson C. Dermal Fibroblast Heterogeneity and Its Contribution to the Skin Repair and Regeneration. Adv Wound Care (New Rochelle) 2022; 11:87-107. [PMID: 33607934 DOI: 10.1089/wound.2020.1287] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Significance: Dermal fibroblasts are the major cell type in the skin's dermal layer. These cells originate from distinct locations of the embryo and reside in unique niches in the dermis. Different dermal fibroblasts exhibit distinct roles in skin development, homeostasis, and wound healing. Therefore, these cells are becoming attractive candidates for cell-based therapies in wound healing. Recent Advances: Human skin dermis comprises multiple fibroblast subtypes, including papillary, reticular, and hair follicle-associated fibroblasts, and myofibroblasts after wounding. Recent studies reveal that these cells play distinct roles in wound healing and contribute to diverse healing outcomes, including nonhealing chronic wound or excessive scar formation, such as hypertrophic scars (HTS) and keloids, with papillary fibroblasts having antiscarring and reticular fibroblast scar-forming properties. Critical Issues: The identities and functions of dermal fibroblast subpopulations in many respects remain unknown. In this review, we summarize the current understanding of dermal fibroblast heterogeneity, including their defined cell markers and dermal niches, dynamic changes, and contributions to skin wound healing, with the emphasis on scarless healing, healing with excessive scars (HTS and keloids), chronic wounds, and the potential application of this heterogeneity for developing cell-based therapies that allow wounds to heal faster with less scarring. Future Directions: Heterogeneous dermal fibroblast populations and their functions are poorly characterized. Refining and advancing our understanding of dermal fibroblast heterogeneity and their participation in skin homeostasis and wound healing may create potential therapeutic applications for nonhealing chronic wounds or wounds that heal with excessive scarring.
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Affiliation(s)
- Meilang Xue
- Sutton Arthritis Research Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, The University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Ruilong Zhao
- Sutton Arthritis Research Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, The University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Lyn March
- Sutton Arthritis Research Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, The University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Christopher Jackson
- Sutton Arthritis Research Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, The University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia
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Chen Q, Li J, Bai S, Wu X, Chen Y. Establishment of Angora rabbits' whisker hair follicle model and optimal culture conditions. Anim Biotechnol 2021; 33:184-192. [PMID: 34904913 DOI: 10.1080/10495398.2021.1988626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
To establish the model of whisker hair follicle culture in vitro and explore the best culture conditions, the whisker hair follicles of Angora rabbits were separated with stereomicroscope and cultured in William's E, DMEM, MEM media. The surface of the cultured whisker hair follicles was not damaged due to manual operation, resulting in the hair shaft's growth. This indicated the success of the in vitro whisker hair follicle model. The hair shaft grew at the fastest rate in the William's E culture (p < 0.05), which was significantly higher than that in the DMEM and MEM media. The hematoxylin-eosin results showed that compared to the William's E group, the atrophy of whisker hair follicles in the DMEM and MEM media was evident, especially in the MEM medium. PCNA immunofluorescence staining was employed to detect the expression of whisker hair follicles. The results showed that the PCNA positive expression of the William's E group was significantly stronger than that of the DMEM and MEM groups. Furthermore, CCK-8 and Annexin V-FITC/PI methods were used to detect the proliferation and apoptosis of the dermal papilla cells (DPCs). The results of this study provide a model for studying the hair growth of fur animals.
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Affiliation(s)
- Qiuran Chen
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China.,Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou, China.,School of Life Sciences, Jiangsu Normal University, Xuzhou, China
| | - Jiali Li
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China.,Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou, China
| | - Shaocheng Bai
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China.,Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou, China
| | - Xinsheng Wu
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China.,Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou, China
| | - Yang Chen
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China.,Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University, Yangzhou, China
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4
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Antioxidants as an Epidermal Stem Cell Activator. Antioxidants (Basel) 2020; 9:antiox9100958. [PMID: 33036398 PMCID: PMC7600937 DOI: 10.3390/antiox9100958] [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: 09/01/2020] [Revised: 10/05/2020] [Accepted: 10/05/2020] [Indexed: 01/18/2023] Open
Abstract
Antioxidants may modulate the microenvironment of epidermal stem cells by reducing the production of reactive oxygen species or by regulating the expression of extracellular matrix protein. The extracellular membrane is an important component of the stem cell niche, and microRNAs regulate extracellular membrane-mediated basal keratinocyte proliferation. In this narrative review, we will discuss several antioxidants such as ascorbic acid, plant extracts, peptides and hyaluronic acid, and their effect on the epidermal stem cell niche and the proliferative potential of interfollicular epidermal stem cells in 3D skin equivalent models.
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Velasco V, Shariati SA, Esfandyarpour R. Microtechnology-based methods for organoid models. MICROSYSTEMS & NANOENGINEERING 2020; 6:76. [PMID: 34567686 PMCID: PMC8433138 DOI: 10.1038/s41378-020-00185-3] [Citation(s) in RCA: 142] [Impact Index Per Article: 28.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/10/2020] [Accepted: 06/03/2020] [Indexed: 05/03/2023]
Abstract
Innovations in biomaterials and stem cell technology have allowed for the emergence of novel three-dimensional (3D) tissue-like structures known as organoids and spheroids. As a result, compared to conventional 2D cell culture and animal models, these complex 3D structures have improved the accuracy and facilitated in vitro investigations of human diseases, human development, and personalized medical treatment. Due to the rapid progress of this field, numerous spheroid and organoid production methodologies have been published. However, many of the current spheroid and organoid production techniques are limited by complexity, throughput, and reproducibility. Microfabricated and microscale platforms (e.g., microfluidics and microprinting) have shown promise to address some of the current limitations in both organoid and spheroid generation. Microfabricated and microfluidic devices have been shown to improve nutrient delivery and exchange and have allowed for the arrayed production of size-controlled culture areas that yield more uniform organoids and spheroids for a higher throughput at a lower cost. In this review, we discuss the most recent production methods, challenges currently faced in organoid and spheroid production, and microfabricated and microfluidic applications for improving spheroid and organoid generation. Specifically, we focus on how microfabrication methods and devices such as lithography, microcontact printing, and microfluidic delivery systems can advance organoid and spheroid applications in medicine.
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Affiliation(s)
- Vanessa Velasco
- Biochemistry Department, Stanford University, Palo Alto, CA USA
| | - S. Ali Shariati
- Department of Biomolecular Engineering, Institute for the Biology of Stem Cells, University of California, Santa Cruz, CA USA
| | - Rahim Esfandyarpour
- Department of Electrical Engineering, University of California, Irvine, CA USA
- Department of Biomedical Engineering, University of California Irvine, Irvine, CA USA
- Henry Samueli School of Engineering, University of California, Irvine, CA USA
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6
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Jang J. 3D Bioprinting and In Vitro Cardiovascular Tissue Modeling. Bioengineering (Basel) 2017; 4:E71. [PMID: 28952550 PMCID: PMC5615317 DOI: 10.3390/bioengineering4030071] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 08/10/2017] [Accepted: 08/11/2017] [Indexed: 12/17/2022] Open
Abstract
Numerous microfabrication approaches have been developed to recapitulate morphologically and functionally organized tissue microarchitectures in vitro; however, the technical and operational limitations remain to be overcome. 3D printing technology facilitates the building of a construct containing biomaterials and cells in desired organizations and shapes that have physiologically relevant geometry, complexity, and micro-environmental cues. The selection of biomaterials for 3D printing is considered one of the most critical factors to achieve tissue function. It has been reported that some printable biomaterials, having extracellular matrix-like intrinsic microenvironment factors, were capable of regulating stem cell fate and phenotype. In particular, this technology can control the spatial positions of cells, and provide topological, chemical, and complex cues, allowing neovascularization and maturation in the engineered cardiovascular tissues. This review will delineate the state-of-the-art 3D bioprinting techniques in the field of cardiovascular tissue engineering and their applications in translational medicine. In addition, this review will describe 3D printing-based pre-vascularization technologies correlated with implementing blood perfusion throughout the engineered tissue equivalent. The described engineering method may offer a unique approach that results in the physiological mimicry of human cardiovascular tissues to aid in drug development and therapeutic approaches.
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Affiliation(s)
- Jinah Jang
- Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Kyungbuk, Korea.
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7
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Kaur P. Hair-follicle dermal papilla and sheath fibroblasts provide a supportive microenvironment for human skin regeneration. Br J Dermatol 2017; 176:1123-1124. [DOI: 10.1111/bjd.15474] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- P. Kaur
- School of Biomedical Sciences; Curtin University; Perth Australia
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Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro. Eur J Cell Biol 2015; 94:483-512. [PMID: 26344860 DOI: 10.1016/j.ejcb.2015.08.001] [Citation(s) in RCA: 177] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 08/11/2015] [Accepted: 08/11/2015] [Indexed: 12/19/2022] Open
Abstract
Advances in cell culture methods, multidisciplinary research, clinical need to replace lost skin tissues and regulatory need to replace animal models with alternative test methods has led to development of three dimensional models of human skin. In general, these in vitro models of skin consist of keratinocytes cultured over fibroblast-populated dermal matrices. Accumulating evidences indicate that mesenchyme-derived signals are essential for epidermal morphogenesis, homeostasis and differentiation. Various studies show that fibroblasts isolated from different tissues in the body are dynamic in nature and are morphologically and functionally heterogeneous subpopulations. Further, these differences seem to be dictated by the local biological and physical microenvironment the fibroblasts reside resulting in "positional identity or memory". Furthermore, the heterogeneity among the fibroblasts play a critical role in scarless wound healing and complete restoration of native tissue architecture in fetus and oral mucosa; and excessive scar formation in diseased states like keloids and hypertrophic scars. In this review, we summarize current concepts about the heterogeneity among fibroblasts and their role in various wound healing environments. Further, we contemplate how the insights on fibroblast heterogeneity could be applied for the development of next generation organotypic skin models.
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Novel Antioxidant Tripeptide "ACQ" Can Prevent UV-Induced Cell Death and Preserve the Number of Epidermal Stem Cells. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015. [PMID: 26199677 PMCID: PMC4496495 DOI: 10.1155/2015/359740] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
We found that tripeptide “ACQ: alanine-cysteine-glutamine” has significant DPPH scavenging activity compared to that of glutathione. Antioxidant effects of ACQ were tested in in vitro and in vivo models. When treated with H2O2, mock treated fibroblasts and keratinocytes showed strong staining by H2DCFA. But, ACQ showed good protective effects against hydrogen peroxide treatment. When mice were fed for 2 or 4 weeks, similar protective effects were observed. In the control group, epidermis was severely damaged by UV irradiation and apoptotic keratinocytes were observed. There were also numerous TUNEL positive cells. But in the ACQ group, epidermis became thicker and there was no sign of severe damage. Interestingly, the number of p63 cells was also higher in ACQ fed mice. To confirm the stem cell rescuing effects of ACQ, three-dimensional skin samples were constructed. Results showed that ACQ increased the expression of integrin α6 and the number of p63 positive cells. These findings showed that ACQ has good antioxidant activity and may increase stem cell activities by the regulation of integrin α6.
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Choi HR, Byun SY, Kwon SH, Park KC. Niche interactions in epidermal stem cells. World J Stem Cells 2015; 7:495-501. [PMID: 25815134 PMCID: PMC4369506 DOI: 10.4252/wjsc.v7.i2.495] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 10/22/2014] [Accepted: 11/03/2014] [Indexed: 02/06/2023] Open
Abstract
Within the epidermis and dermis of the skin, cells secrete and are surrounded by the extracellular matrix (ECM), which provides structural and biochemical support. The ECM of the epidermis is the basement membrane, and collagen and other dermal components constitute the ECM of the dermis. There is significant variation in the composition of the ECM of the epidermis and dermis, which can affect “cell to cell” and “cell to ECM” interactions. These interactions, in turn, can influence biological responses, aging, and wound healing; abnormal ECM signaling likely contributes to skin diseases. Thus, strategies for manipulating cell-ECM interactions are critical for treating wounds and a variety of skin diseases. Many of these strategies focus on epidermal stem cells, which reside in a unique niche in which the ECM is the most important component; interactions between the ECM and epidermal stem cells play a major role in regulating stem cell fate. As they constitute a major portion of the ECM, it is likely that integrins and type IV collagens are important in stem cell regulation and maintenance. In this review, we highlight recent research-including our previous work-exploring the role that the ECM and its associated components play in shaping the epidermal stem cell niche.
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11
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Kim DS, Cho HJ, Yang SK, Shin JW, Huh CH, Park KC. Insulin-like growth factor-binding protein contributes to the proliferation of less proliferative cells in forming skin equivalents. Tissue Eng Part A 2009; 15:1075-80. [PMID: 18803482 DOI: 10.1089/ten.tea.2008.0236] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
In this study, the effects and the mediating factors of dermal cells on the epidermal regenerative ability were investigated. Human epidermal cells were separated into rapidly adhering (RA) cells and slowly adhering (SA) cells and used for culturing skin equivalents (SEs). For dermal part, normal human fibroblasts, dermal sheath cells (DSCs), and dermal papilla cells were used. SEs produced using SA cells and DSCs showed a thicker epidermis and higher expressions of alpha(6)- and beta1-integrin than SEs using SA cells and normal fibroblasts showed. We hypothesized that DSCs may secrete specific cytokines that can influence the regenerative potential of epidermal cells, and compared cytokine secretion by DSCs and normal human fibroblasts. Using RayBio human cytokine antibody array C (series 1000), 120 cytokines were tested. Results showed that DSCs produced a much greater amount of insulin-like growth factor-binding protein (IGFBP-2), angiogenin, and BMP-6 than normal human fibroblasts produced. On the basis of the cytokine antibody array, we next investigated whether IGFBP-2, angiogenin, or BMP-6 has effects on SEs reconstruction. The addition of IGFBP-2 induced a thicker and more mature epidermis and higher expressions of alpha(6)- and beta1-integrin, whereas BMP-6 exhibited little effect. Thus, the SEs with IGFBP-2 showed almost the same morphology of the SEs using DSCs. Further, p63, a putative keratinocyte stem cell marker, was more frequently observed in the basal layer of SE with IGFBP-2. In conclusion, IGFBP-2 is a major factor from DSCs that affects epidermal regenerative capacity of skin and may play an important role for stemness maintenance in human epidermal keratinocytes.
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Affiliation(s)
- Dong-Seok Kim
- Department of Biochemistry, College of Medicine, Chung-Ang University, Seoul, Korea
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12
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Han I, Shim KJ, Kim JY, Im SU, Sung YK, Kim M, Kang IK, Kim JC. Effect of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Nanofiber Matrices Cocultured With Hair Follicular Epithelial and Dermal Cells for Biological Wound Dressing. Artif Organs 2007; 31:801-8. [DOI: 10.1111/j.1525-1594.2007.00466.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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13
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Richardson GD, Arnott EC, Whitehouse CJ, Lawrence CM, Reynolds AJ, Hole N, Jahoda CAB. Plasticity of rodent and human hair follicle dermal cells: implications for cell therapy and tissue engineering. J Investig Dermatol Symp Proc 2005; 10:180-3. [PMID: 16382659 DOI: 10.1111/j.1087-0024.2005.10101.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
The dermal components of the hair follicle exhibit a number of stem cell properties, including regenerative potential, roles in wound healing and the ability to produce a functional dermis. Here we examine the stem cell phenomenon of plasticity, focusing on recent observations of in vitro plasticity of dermal papilla and sheath cells, including previously unpublished data of neuronal-like differentiation. We then briefly address the implications of the stem cell potential of hair follicle dermal cells for the field of tissue engineering.
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Affiliation(s)
- Gavin D Richardson
- School of Biological & Biomedical Sciences, University of Durham, Durham, NC, USA
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Mayuzumi N, Shigihara T, Ikeda S, Ogawa H. R162W mutation of keratin 9 in a family with autosomal dominant palmoplantar keratoderma with unique histologic features. J Investig Dermatol Symp Proc 1999; 4:150-2. [PMID: 10536990 DOI: 10.1038/sj.jidsp.5640199] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Recurrent R162W mutation ofkeratin 9 has been reported in multiple families with epidermolytic hyperkeratosis (EHK)-type hereditary palmoplantar keratoderma (PPK). Recently, we have observed a family whose members showed autosomal-dominant PPK with unique histologic features such as rounded, dissociated, and slightly eosinophilic keratinocytes at the middle spinous and granular layers of epidermis, but without the distinct EHK phenotype. To investigate the genotype-phenotype correlation in this family, we searched for a mutation of keratin 9 and found R162W substitution in the coiled 1A region. This mutation was not detected in 50 control individuals. These results may further our understanding of the pathogenesis of EHK.
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Affiliation(s)
- N Mayuzumi
- Department of Dermatology, Juntendo University, School of Medicine, Tokyo, Japan
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