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Wang X, Wang Q, Meng L, Tian R, Guo H, Tan Z, Tan Y. Biodistribution-based Administration of cGMP-compliant Human Umbilical Cord Mesenchymal Stem Cells Affects the Therapeutic Effect of Wound Healing. Stem Cell Rev Rep 2024; 20:329-346. [PMID: 37889447 DOI: 10.1007/s12015-023-10644-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND Although mesenchymal stem cells (MSCs) are used as therapeutic agents for skin injury therapy, few studies have reported the effects of dosing duration and delivery frequency on wound healing. In addition, before the clinical application of MSCs, it is important to assess whether their usage might influence tumor occurrence. METHODS We described the metabolic patterns of subcutaneous injection of hUC-MSCs using fluorescence tracing and qPCR methods and applied them to the development of drug delivery strategies for promoting wound healing. RESULTS (i) We developed cGMP-compliant hUC-MSC products with critical quality control points for wound healing; (ii) The products did not possess any tumorigenic or tumor-promoting/inhibiting ability in vivo; (iii) Fluorescence tracing and qPCR analyses showed that the subcutaneous application of hUC-MSCs did not result in safety-relevant biodistribution or ectopic migration; (iv) Reinjecting hUC-MSCs after significant consumption significantly improved reepithelialization and dermal regeneration. CONCLUSIONS Our findings provided a reference for controlling the quality of MSC products used for wound healing and highlighted the importance of delivery time and frequency for designing in vivo therapeutic studies.
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Affiliation(s)
- Xin Wang
- Qilu Cell Therapy Technology Co., Ltd, Gangyuan 6th Road, Licheng District, Ji'nan, Shandong, 250000, People's Republic of China
| | - Qiuhong Wang
- Qilu Cell Therapy Technology Co., Ltd, Gangyuan 6th Road, Licheng District, Ji'nan, Shandong, 250000, People's Republic of China
| | - Lingjiao Meng
- Qilu Cell Therapy Technology Co., Ltd, Gangyuan 6th Road, Licheng District, Ji'nan, Shandong, 250000, People's Republic of China
| | - Ruifeng Tian
- Qilu Cell Therapy Technology Co., Ltd, Gangyuan 6th Road, Licheng District, Ji'nan, Shandong, 250000, People's Republic of China
| | - Huizhen Guo
- Qilu Cell Therapy Technology Co., Ltd, Gangyuan 6th Road, Licheng District, Ji'nan, Shandong, 250000, People's Republic of China
| | - Zengqi Tan
- School of Medicine, Northwest University, Xi'an, China
| | - Yi Tan
- Qilu Cell Therapy Technology Co., Ltd, Gangyuan 6th Road, Licheng District, Ji'nan, Shandong, 250000, People's Republic of China.
- Shandong Yinfeng Life Science Research Institute, Ji'nan, People's Republic of China.
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Lambertini M, Ricci C, Corti B, Veronesi G, Quaglino P, Ribero S, Pellacani G, Hrvatin Stancic B, Campione E, Dika E. Follicular colonization in melanocytic nevi and melanoma: A literature review. J Cutan Pathol 2023. [PMID: 36820529 DOI: 10.1111/cup.14415] [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: 11/22/2022] [Revised: 02/11/2023] [Accepted: 02/21/2023] [Indexed: 02/24/2023]
Abstract
The lentiginous spread of melanocytes into the hair follicle can be observed in a number of benign melanocytic neoplasms such as in nevi but also in sun-induced melanocytic hyperplasia and melanoma. The follicular colonization by melanocytes in melanoma is classified into three distinct patterns: primary follicular melanoma, melanoma with folliculotropism, and invasive melanoma arising from melanoma in situ with folliculotropism. The role of follicular colonization in melanoma pathologic staging is still a matter of debate though the description of the latter has been recommended by the International Collaboration on Cancer Reporting. In this review, we will discuss the role of follicular colonization in melanoma and melanocytic nevi as well as the facts and controversies regarding this topic.
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Affiliation(s)
- Martina Lambertini
- Melanoma Centre, Dermatology, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
- Dermatology, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Costantino Ricci
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
- Pathology Unit, Maggiore Hospital, AUSL Bologna, Bologna, Italy
| | - Barbara Corti
- Pathology Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Giulia Veronesi
- Melanoma Centre, Dermatology, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
- Dermatology, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Pietro Quaglino
- Dermatology Clinic, Department of medical sciences, University of Turin, Turin, Italy
| | - Simone Ribero
- Dermatology Clinic, Department of medical sciences, University of Turin, Turin, Italy
| | - Giovanni Pellacani
- Dermatology Clinic, Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza Medical School, Sapienza University of Rome, Rome, Italy
| | - Bor Hrvatin Stancic
- Dermatovenerology Department, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Elena Campione
- Dermatology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Emi Dika
- Melanoma Centre, Dermatology, IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
- Dermatology, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy
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Lin L, He E, Wang H, Guo W, Wu Z, Huang K, Zhao Q. Intravenous Transplantation of Human Hair Follicle-Derived Mesenchymal Stem Cells Ameliorates Trabecular Bone Loss in Osteoporotic Mice. Front Cell Dev Biol 2022; 10:814949. [PMID: 35359450 PMCID: PMC8960386 DOI: 10.3389/fcell.2022.814949] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 02/21/2022] [Indexed: 12/20/2022] Open
Abstract
Background: Hair follicles harbor a rich autologous stem cell pool and human hair follicle-derived mesenchymal stem cells (hHF-MSCs) have multi-lineage differentiation potential. Many sources of MSCs include hHF-MSCs have been attractive candidates for cell therapy, regenerative medicine and tissue engineering. The present study is to explore the effect of intravenous transplantation of hHF-MSCs on bone mass in osteoporotic mice and its mechanism, and provides prospects for clinical applications for the treatment of osteoporosis with hHF-MSCs. Methods: Physically pull out about 20 hairs with intact hair follicles from the occipital area of the scalp of healthy volunteers, and extract hair follicle-derived fibroblast-like cells. These cells were cultured and characterized in vitro. Intravenous injection of hHF-MSCs was performed on ovariectomy-induced and age-related osteoporotic SCID mice for osteoporosis treatment. The mice were sacrificed 7 weeks after the second injection and samples were collected. The long bones and L1 vertebrae were collected for micro-CT scan, histomorphometry and immunohistochemical analysis. Peripheral serum were collected for ELISA analysis and antibody array. Results: Hair follicle-derived fibroblast-like cells were defined as hHF-MSCs. Intravenous transplantation of hHF-MSCs can better restores trabecular bone mass in osteoporotic mice. The double calcein labeling assay, trap staining of bones and ELISA analysis in peripheral serum showed enhanced bone formation and weakened bone resorption after transplantation. Antibody array and immunohistochemical analysis showed that several cytokines including OPG, Wnt2b, Noggin, VCAM-1 and RANKL might be involved in this process. Conclusion: Human HF-MSCs transplantation can combat trabecular bone loss induced by menopause and aging in mice. And the above mechanism that hHF-MSCs transplantation inhibits bone resorption and promote bone formation is related to OPG, Wnt2b, VCAM-1, Noggin and RANKL.
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Affiliation(s)
- Longshuai Lin
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Enjun He
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongjie Wang
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weihong Guo
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhenkai Wu
- Department of Pediatric Orthopaedics, Shanghai Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Zhenkai Wu, ; Kai Huang, ; Qinghua Zhao,
| | - Kai Huang
- Department of Orthopedics, Zhabei Central Hospital of Jing’an District, Shanghai, China
- *Correspondence: Zhenkai Wu, ; Kai Huang, ; Qinghua Zhao,
| | - Qinghua Zhao
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Zhenkai Wu, ; Kai Huang, ; Qinghua Zhao,
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Liu Q, Lv C, Jiang Y, Luo K, Gao Y, Liu J, Zhang X, Mohammad Omar J, Jin S. From hair to liver: emerging application of hair follicle mesenchymal stem cell transplantation reverses liver cirrhosis by blocking the TGF-β/Smad signaling pathway to inhibit pathological HSC activation. PeerJ 2022; 10:e12872. [PMID: 35186473 PMCID: PMC8855721 DOI: 10.7717/peerj.12872] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 01/11/2022] [Indexed: 01/10/2023] Open
Abstract
Liver cirrhosis (LC) involves multiple systems throughout the body, and patients with LC often die of multiple organ failure. However, few drugs are useful to treat LC. Hair follicle mesenchymal stem cells (HF-MSCs) are derived from the dermal papilla and the bulge area of hair follicles and are pluripotent stem cells in the mesoderm with broad prospects in regenerative medicine. As an emerging seed cell type widely used in skin wound healing and plastic surgery, HF-MSCs show considerable prospects in the treatment of LC due to their proliferation and multidirectional differentiation capabilities. We established an LC model in C57BL/6J mice by administering carbon tetrachloride (CCl4) and injected HF-MSCs through the tail vein to explore the therapeutic effects and potential mechanisms of HF-MSCs on LC. Here, we found that HF-MSCs improved liver function and ameliorated the liver pathology of LC. Notably, PKH67-labeled HF-MSCs were detected in the injured liver and expressed the hepatocyte-specific markers cytokeratin 18 (CK18) and albumin (ALB). In addition, in contrast to that in the LC group, the α-SMA expression showed a decreasing trend in the treatment group in vitro and in vivo, indicating that the pathological activation of hepatic stellate cells (HSCs) was inhibited by HF-MSC treatment. Moreover, the levels of transforming growth factor β (TGF-β1) and p-Smad3, a signaling molecule downstream of TGF-β1, were increased in mice with LC, while HF-MSC treatment reversed these changes in vivo and in vitro. Based on these findings, HF-MSCs may reverse LC by blocking the TGF-β/Smad pathway and inhibiting the pathological activation of HSCs, which may provide evidence for the application of HF-MSCs to treat LC.
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Affiliation(s)
- Qi Liu
- Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chengqian Lv
- Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yanan Jiang
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy of Harbin Medical University, Harbin, China,Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
| | - Kunpeng Luo
- Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yang Gao
- Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jingyang Liu
- Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xu Zhang
- Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jan Mohammad Omar
- Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Shizhu Jin
- Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Zhai X, Gong M, Peng Y, Yang D. Effects of UV Induced-Photoaging on the Hair Follicle Cycle of C57BL6/J Mice. Clin Cosmet Investig Dermatol 2021; 14:527-539. [PMID: 34040410 PMCID: PMC8140904 DOI: 10.2147/ccid.s310487] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 05/05/2021] [Indexed: 12/16/2022]
Abstract
Purpose To study the changes in the hair follicle cycle and related stem cells induced by photoaging to establish a mouse model of senescence in hair follicles. Methods There were 54 C57BL6/J mice randomly divided into three groups. The UVA group and the UVB group underwent photoaging induced by UV lamps for 8 weeks. Changes in skin and the hair follicle cycle were compared by physical signs, dermoscopy, and hematoxylin and eosin and Masson's staining in each group. Western blot, immunohistochemistry, and RT-qPCR were carried out to test canonical proteins and gene expression of the Wnt signaling pathway in the samples. Immunofluorescence was chosen to show variations in the stem cells related to the hair follicle cycle. Results There were more gray hairs in the UVA group than the other groups (P<0.05). Both diameter of the hair shaft and depth of hair root were significantly decreased in the UV groups (P<0.05). Stem cells and melanocytes of the hair follicles were reduced in the UVA group. UV, especially UVB, up-regulated the expression of the Wnt signaling pathway and prolonged anagen and telogen phases in the hair follicles, compared with the control group (P<0.05). Conclusion By decreasing the number of stem cells related to hair follicles, UVA induces hair follicle photoaging characterized by hair follicle miniaturization and gray hairs. UV up-regulated the expression of the Wnt signaling pathway, and the hair follicle cycle was significantly prolonged by UVB.
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Affiliation(s)
- Xu Zhai
- Department of Plastic Surgery, The 2nd Hospital of Harbin Medical University, Harbin, People's Republic of China
| | - Meihua Gong
- Department of Plastic Surgery, The 2nd Hospital of Harbin Medical University, Harbin, People's Republic of China.,Department of Plastic and Cosmetic Surgery, Shenzhen People's Hospital, Second Affiliated Hospital of Jinan University Medical College, Shenzhen, People's Republic of China
| | - Yixuan Peng
- Department of Plastic Surgery, The 2nd Hospital of Harbin Medical University, Harbin, People's Republic of China
| | - Daping Yang
- Department of Plastic Surgery, The 2nd Hospital of Harbin Medical University, Harbin, People's Republic of China
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Žnidarič M, Žurga ŽM, Maver U. Design of In Vitro Hair Follicles for Different Applications in the Treatment of Alopecia-A Review. Biomedicines 2021; 9:biomedicines9040435. [PMID: 33923738 PMCID: PMC8072628 DOI: 10.3390/biomedicines9040435] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 04/08/2021] [Accepted: 04/13/2021] [Indexed: 12/19/2022] Open
Abstract
The hair research field has seen great improvement in recent decades, with in vitro hair follicle (HF) models being extensively developed. However, due to the cellular complexity and number of various molecular interactions that must be coordinated, a fully functional in vitro model of HFs remains elusive. The most common bioengineering approach to grow HFs in vitro is to manipulate their features on cellular and molecular levels, with dermal papilla cells being the main focus. In this study, we focus on providing a better understanding of HFs in general and how they behave in vitro. The first part of the review presents skin morphology with an emphasis on HFs and hair loss. The remainder of the paper evaluates cells, materials, and methods of in vitro growth of HFs. Lastly, in vitro models and assays for evaluating the effects of active compounds on alopecia and hair growth are presented, with the final emphasis on applications of in vitro HFs in hair transplantation. Since the growth of in vitro HFs is a complicated procedure, there is still a great number of unanswered questions aimed at understanding the long-term cycling of HFs without losing inductivity. Incorporating other regions of HFs that lead to the successful formation of different hair classes remains a difficult challenge.
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Zaki AKA, Almundarij TI, Abo-Aziza FAM. Comparative characterization and osteogenic / adipogenic differentiation of mesenchymal stem cells derived from male rat hair follicles and bone marrow. CELL REGENERATION (LONDON, ENGLAND) 2020; 9:13. [PMID: 32778979 PMCID: PMC7417469 DOI: 10.1186/s13619-020-00051-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 05/06/2020] [Indexed: 01/11/2023]
Abstract
Clinical applications of cell therapy and tissue regeneration under different conditions need a multiplicity of adult stem cell sources. Up to date, little is available on the comparative isolation, characterization, proliferation, rapid amplification, and osteogenic/adipogenic differentiation of rat mesenchymal stem cells (MSCs) isolated from living bulge cells of the hair follicle (HF) and bone marrow (BM) from the same animal. This work hopes to use HF-MSCs as an additional adult stem cell source for research and application. After reaching 80% confluence, the cell counting, viability %, and yields of HF-MSCs and BM-MSCs were nearly similar. The viability % was 91.41 ± 2.98 and 93.11 ± 3.06 while the cells yield of initial seeding was 33.15 ± 2.76 and 34.22 ± 3.99 and of second passage was 28.76 ± 1.01 and 29.56 ± 3.11 for HF-MSCs and BM-MSCs respectively. Clusters of differentiation (CDs) analysis revealed that HF-MSCs were positively expressed CD34, CD73 and CD200 and negatively expressed CD45. BM-MSCs were positively expressed CD73 and CD200 and negatively expressed of CD34 and CD45. The proliferation of HF-MSCs and BM-MSCs was determined by means of incorporation of Brd-U, population doubling time (PDT) assays and the quantity of formazan release. The percentage of Brd-U positive cells and PDT were relatively similar in both types of cells. The proliferation, as expressed by the quantity of formazan assay in confluent cells, revealed that the quantity of release by BM-MSCs was slightly higher than HF-MSCs. Adipogenic differentiated BM-MSCs showed moderate accumulation of oil red-O stained lipid droplets when compared to that of HF-MSCs which exhibited high stain. The total lipid concentration was significantly higher in adipogenic differentiated HF-MSCs than BM-MSCs (P < 0.05). It was found that activity of bone alkaline phosphatase and calcium concentration were significantly higher (P < 0.01 and P < 0.05 respectively) in osteogenic differentiated BM-MSCs than that of HF-MSCs. The present findings demonstrate that the HF-MSCs are very similar in most tested characteristics to BM-MSCs with the exception of differentiation. Additionally; no issues have been reported during the collection of HF-MSCs. Therefore, the HF may represent a suitable and accessible source for adult stem cells and can be considered an ideal cell source for adipogenesis research.
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Affiliation(s)
- Abdel Kader A Zaki
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia.
- Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
| | - Tariq I Almundarij
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Faten A M Abo-Aziza
- Department of Parasitology and Animal Diseases, Veterinary Research Division, National Research Centre, Cairo, Egypt
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Wang B, Liu XM, Liu ZN, Wang Y, Han X, Lian AB, Mu Y, Jin MH, Liu JY. Human hair follicle-derived mesenchymal stem cells: Isolation, expansion, and differentiation. World J Stem Cells 2020; 12:462-470. [PMID: 32742563 PMCID: PMC7360986 DOI: 10.4252/wjsc.v12.i6.462] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/18/2020] [Accepted: 05/29/2020] [Indexed: 02/06/2023] Open
Abstract
Hair follicles are easily accessible skin appendages that protect against cold and potential injuries. Hair follicles contain various pools of stem cells, such as epithelial, melanocyte, and mesenchymal stem cells (MSCs) that continuously self-renew, differentiate, regulate hair growth, and maintain skin homeostasis. Recently, MSCs derived from the dermal papilla or dermal sheath of the human hair follicle have received attention because of their accessibility and broad differentiation potential. In this review, we describe the applications of human hair follicle-derived MSCs (hHF-MSCs) in tissue engineering and regenerative medicine. We have described protocols for isolating hHF-MSCs from human hair follicles and their culture condition in detail. We also summarize strategies for maintaining hHF-MSCs in a highly proliferative but undifferentiated state after repeated in vitro passages, including supplementation of growth factors, 3D suspension culture technology, and 3D aggregates of MSCs. In addition, we report the potential of hHF-MSCs in obtaining induced smooth muscle cells and tissue-engineered blood vessels, regenerated hair follicles, induced red blood cells, and induced pluripotent stem cells. In summary, the abundance, convenient accessibility, and broad differentiation potential make hHF-MSCs an ideal seed cell source of regenerative medical and cell therapy.
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Affiliation(s)
- Bo Wang
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Xiao-Mei Liu
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Zi-Nan Liu
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Yuan Wang
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Xing Han
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Ao-Bo Lian
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Ying Mu
- Research Center for Analytical Instrumentation, Institute of Cyber-Systems and Control, State Key Laboratory of Industrial Control Technology, Zhejiang University, Hangzhou 310000, Zhejiang Province, China
| | - Ming-Hua Jin
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Jin-Yu Liu
- Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, Jilin Province, China
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Khalil S, Ariel Gru A, Saavedra AP. Cutaneous extramedullary haematopoiesis: Implications in human disease and treatment. Exp Dermatol 2019; 28:1201-1209. [DOI: 10.1111/exd.14013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 06/26/2019] [Accepted: 07/11/2019] [Indexed: 12/17/2022]
Affiliation(s)
- Shadi Khalil
- Department of Dermatology University of Virginia School of Medicine Charlottesville Virginia
| | - Alejandro Ariel Gru
- Department of Pathology University of Virginia School of Medicine Charlottesville Virginia
| | - Arturo P. Saavedra
- Department of Dermatology University of Virginia School of Medicine Charlottesville Virginia
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10
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Farivar S, Ramezankhani R, Mohajerani E, Ghazimoradi MH, Shiari R. Gene Expression Analysis of Chondrogenic Markers in Hair Follicle Dermal Papillae Cells Under the Effect of Laser Photobiomodulation and the Synovial Fluid. J Lasers Med Sci 2019; 10:171-178. [PMID: 31749941 DOI: 10.15171/jlms.2019.27] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Introduction: Regarding the limited ability of the damaged cartilage cells to self-renew, which is due to their specific tissue structure, subtle damages can usually cause diseases such as osteoarthritis. In this work, using laser photobiomodulation and an interesting source of growth factors cocktail called the synovial fluid, we analyzed the chondrogenic marker genes in treated hair follicle dermal papilla cells as an accessible source of cells with relatively high differentiation potential. Methods: Dermal papilla cells were isolated from rat whisker hair follicle (Rattus norvegicus) and established cell cultures were treated with a laser (gallium aluminum arsenide diode Laser (λ=780 nm, 30 mW) at 5 J/cm2 ), the synovial fluid, and a combination of both. After 1, 4, 7, and 14 days, the morphological changes were evaluated and the expression levels of four chondrocyte marker genes (Col2a1, Sox-9, Col10a1, and Runx-2) were assessed by the quantitative real-time polymerase chain reaction. Results: It was monitored that treating cells with laser irradiation can accelerate the rate of proliferation of cells. The morphology of the cells treated with the synovial fluid altered considerably as in the fourth day they surprisingly looked like cultured articular chondrocytes. The gene expression analysis showed that all genes were up-regulated until the day 14 following the treatments although not equally in all the cell groups. Moreover, the cell groups treated with both irradiation and the synovial fluid had a significantly augmented expression in gene markers. Conclusion: Based on the gene expression levels and the morphological changes, we concluded that the synovial fluid can have the potential to make the dermal papilla cells to most likely mimic the chondrogenic and/or osteogenic differentiation, although this process seems to be augmented by the irradiation of the low-level laser.
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Affiliation(s)
- Shirin Farivar
- Department of Molecular and Cell Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, General Campus, Tehran, Iran
| | - Roya Ramezankhani
- Department of Molecular and Cell Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, General Campus, Tehran, Iran
| | - Ezedin Mohajerani
- Laser and Plasma Research Institute, Shahid Beheshti University, General Campus, Tehran, Iran
| | - Mohammad Hosein Ghazimoradi
- Department of Molecular and Cell Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, General Campus, Tehran, Iran
| | - Reza Shiari
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Cho H, Blatchley MR, Duh EJ, Gerecht S. Acellular and cellular approaches to improve diabetic wound healing. Adv Drug Deliv Rev 2019; 146:267-288. [PMID: 30075168 DOI: 10.1016/j.addr.2018.07.019] [Citation(s) in RCA: 146] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Revised: 07/23/2018] [Accepted: 07/30/2018] [Indexed: 02/06/2023]
Abstract
Chronic diabetic wounds represent a huge socioeconomic burden for both affected individuals and the entire healthcare system. Although the number of available treatment options as well as our understanding of wound healing mechanisms associated with diabetes has vastly improved over the past decades, there still remains a great need for additional therapeutic options. Tissue engineering and regenerative medicine approaches provide great advantages over conventional treatment options, which are mainly aimed at wound closure rather than addressing the underlying pathophysiology of diabetic wounds. Recent advances in biomaterials and stem cell research presented in this review provide novel ways to tackle different molecular and cellular culprits responsible for chronic and nonhealing wounds by delivering therapeutic agents in direct or indirect ways. Careful integration of different approaches presented in the current article could lead to the development of new therapeutic platforms that can address multiple pathophysiologic abnormalities and facilitate wound healing in patients with diabetes.
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Affiliation(s)
- Hongkwan Cho
- Wilmer Ophthalmologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Michael R Blatchley
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Institute for NanoBioTechnology, Johns Hopkins University Baltimore, MD, USA
| | - Elia J Duh
- Wilmer Ophthalmologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sharon Gerecht
- Department of Chemical and Biomolecular Engineering, Institute for NanoBioTechnology, Johns Hopkins University Baltimore, MD, USA.
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Golchin A, Farahany TZ, Khojasteh A, Soleimanifar F, Ardeshirylajimi A. The Clinical Trials of Mesenchymal Stem Cell Therapy in Skin Diseases: An Update and Concise Review. Curr Stem Cell Res Ther 2019; 14:22-33. [PMID: 30210006 DOI: 10.2174/1574888x13666180913123424] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Revised: 08/15/2018] [Accepted: 09/04/2018] [Indexed: 12/13/2022]
Abstract
The skin is one of the crucial body organs with anatomy and physiology linked to various disorders including congenital and acquired diseases. Nowadays, mesenchymal stem cell (MSCs)- based therapy has appeared as a promising therapeutic field, in which many see opportunities to cure the costliest and incurable diseases. However, one question to be asked is that if the use of MSCs in clinical trials studies and diseases treatment has improved. In this study, the clinical trials using MSCs in skin diseases were reviewed. A remarkable number of clinical trial studies are in progress in this field; however, only a few of them have led to tangible benefits for patients. The relevant papers and ongoing clinical trials that address MSC's therapeutic goals for various skin disorders were examined. This review can be very useful for both the dermatologists and basic skin researchers interested in contributing to stem cell-based therapeutic researches in the area of skin disorders.
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Affiliation(s)
- Ali Golchin
- Department of Tissue engineering and Applied Cell Sciences, Student Research Committee, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tahereh Z Farahany
- Department of Biology, School of Advanced Technologies in Medicine, Islamic Azad University Medical Branch of Tehran, Tehran, Iran
| | - Arash Khojasteh
- Department of Tissue engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Soleimanifar
- Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran
| | - Abdolreza Ardeshirylajimi
- Department of Tissue engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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13
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Ohyama M. Use of human intra-tissue stem/progenitor cells and induced pluripotent stem cells for hair follicle regeneration. Inflamm Regen 2019; 39:4. [PMID: 30834027 PMCID: PMC6388497 DOI: 10.1186/s41232-019-0093-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 01/23/2019] [Indexed: 01/07/2023] Open
Abstract
Background The hair follicle (HF) is a unique miniorgan, which self-renews for a lifetime. Stem cell populations of multiple lineages reside within human HF and enable its regeneration. In addition to resident HF stem/progenitor cells (HFSPCs), the cells with similar biological properties can be induced from human-induced pluripotent stem cells (hiPSCs). As approaches to regenerate HF by combining HF-derived cells have been established in rodents and a huge demand exists to treat hair loss diseases, attempts have been made to bioengineer human HF using HFSPCs or hiPSCs. Main body of the abstract The aim of this review is to comprehensively summarize the strategies to regenerate human HF using HFSPCs or hiPSCs. HF morphogenesis and regeneration are enabled by well-orchestrated epithelial-mesenchymal interactions (EMIs). In rodents, various combinations of keratinocytes with mesenchymal (dermal) cells with trichogenic capacity, which were transplanted into in vivo environment, have successfully generated HF structures. The regeneration efficiency was higher, when epithelial or dermal HFSPCs were adopted. The success in HF formation most likely depended on high receptivity to trichogenic dermal signals and/or potent hair inductive capacity of HFSPCs. In theory, the use of epithelial HFSPCs in the bulge area and dermal papilla cells, their precursor cells in the dermal sheath, or trichogenic neonatal dermal cells should elicit intense EMI sufficient for HF formation. However, technical hurdles, represented by the limitation in starting materials and the loss of intrinsic properties during in vitro expansion, hamper the stable reconstitution of human HFs with this approach. Several strategies, including the amelioration of culture condition or compartmentalization of cells to strengthen EMI, can be conceived to overcome this obstacle. Obviously, use of hiPSCs can resolve the shortage of the materials once reliable protocols to induce wanted HFSPC subsets have been developed, which is in progress. Taking advantage of their pluripotency, hiPSCs may facilitate previously unthinkable approaches to regenerate human HFs, for instance, via bioengineering of 3D integumentary organ system, which can also be applied for the treatment of other diseases. Short conclusion Further development of methodologies to reproduce bona fide EMI in HF formation is indispensable. However, human HFSPCs and hiPSCs hold promise as materials for human HF regeneration.
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Affiliation(s)
- Manabu Ohyama
- Department of Dermatology, Kyorin University Faculty of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611 Japan
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14
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Hair Follicle Dermal Cells Support Expansion of Murine and Human Embryonic and Induced Pluripotent Stem Cells and Promote Haematopoiesis in Mouse Cultures. Stem Cells Int 2018; 2018:8631432. [PMID: 30154866 PMCID: PMC6098861 DOI: 10.1155/2018/8631432] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Accepted: 04/26/2018] [Indexed: 12/26/2022] Open
Abstract
In the hair follicle, the dermal papilla (DP) and dermal sheath (DS) support and maintain proliferation and differentiation of the epithelial stem cells that produce the hair fibre. In view of their regulatory properties, in this study, we investigated the interaction between hair follicle dermal cells (DP and DS) and embryonic stem cells (ESCs); induced pluripotent stem cells (iPSCs); and haematopoietic stem cells. We found that coculture of follicular dermal cells with ESCs or iPSCs supported their prolonged maintenance in an apparently undifferentiated state as established by differentiation assays, immunocytochemistry, and RT-PCR for markers of undifferentiated ESCs. We further showed that cytokines that are involved in ESC support are also expressed by cultured follicle dermal cells, providing a possible explanation for maintenance of ES cell stemness in cocultures. The same cytokines were expressed within follicles in situ in a pattern more consistent with a role in follicle growth activities than stem cell maintenance. Finally, we show that cultured mouse follicle dermal cells provide good stromal support for haematopoiesis in an established coculture model. Human follicular dermal cells represent an accessible and readily propagated source of feeder cells for pluripotent and haematopoietic cells and have potential for use in clinical applications.
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15
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Krygowska AA, Castellano E. PI3K: A Crucial Piece in the RAS Signaling Puzzle. Cold Spring Harb Perspect Med 2018; 8:cshperspect.a031450. [PMID: 28847905 DOI: 10.1101/cshperspect.a031450] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
RAS proteins are key signaling switches essential for control of proliferation, differentiation, and survival of eukaryotic cells. RAS proteins are mutated in 30% of human cancers. In addition, mutations in upstream or downstream signaling components also contribute to oncogenic activation of the pathway. RAS proteins exert their functions through activation of several signaling pathways and dissecting the contributions of these effectors in normal cells and in cancer is an ongoing challenge. In this review, we summarize our current knowledge about how RAS regulates type I phosphatidylinositol 3-kinase (PI3K), one of the main RAS effectors. RAS signaling through PI3K is necessary for normal lymphatic vasculature development and for RAS-induced transformation in vitro and in vivo, especially in lung cancer, where it is essential for tumor initiation and necessary for tumor maintenance.
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Affiliation(s)
- Agata Adelajda Krygowska
- Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom
| | - Esther Castellano
- Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom
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16
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Call M, Meyer EA, Kao WW, Kruse FE, Schlӧtzer-Schrehardt U. Hair Follicle Stem Cell Isolation and Expansion. Bio Protoc 2018; 8:e2848. [PMID: 29951567 PMCID: PMC6017999 DOI: 10.21769/bioprotoc.2848] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Revised: 04/22/2018] [Accepted: 04/24/2018] [Indexed: 01/15/2023] Open
Abstract
Stem cells are widely used for numerous clinical applications including limbal stem cell deficiency. Stem cell derived from the bulge region of the hair follicle have the ability to differentiate into a variety of cell types including interfollicular epidermis, hair follicle structures, sebaceous glands and corneal epithelial cells when provided the appropriate cues. Hair follicle stem cells are being studied as a valuable source of autologous stem cells to treat disease. The protocol described below details the isolation and expansion of these cells for eventual clinical application. We used a dual-reporter mouse model to visualize both isolation and eventual differentiation of these cells in a limbal stem cell-deficient mouse model.
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Affiliation(s)
- Mindy Call
- Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, USA
| | - Ewa Anna Meyer
- Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany
- Department of Ophthalmology, Paracelsus Medical University, Nuremberg, Germany
| | - Winston W. Kao
- Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, USA
| | - Friedrich E. Kruse
- Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany
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17
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Tao Y, Yang Q, Wang L, Zhang J, Zhu X, Sun Q, Han Y, Luo Q, Wang Y, Guo X, Wu J, Li B, Yang X, He L, Ma G. β-catenin activation in hair follicle dermal stem cells induces ectopic hair outgrowth and skin fibrosis. J Mol Cell Biol 2018; 11:26-38. [DOI: 10.1093/jmcb/mjy032] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 05/12/2018] [Indexed: 02/01/2023] Open
Abstract
Abstract
Hair follicle dermal sheath (DS) harbors hair follicle dermal stem cells (hfDSCs), which can be recruited to replenish DS and dermal papilla (DP). Cultured DS cells can differentiate into various cell lineages in vitro. However, it is unclear how its plasticity is modulated in vivo. Wnt/β-catenin signaling plays an important role in maintaining stem cells of various lineages and is required for HF development and regeneration. Here we report that activation of β-catenin in DS generates ectopic HF outgrowth (EF) by reprogramming HF epidermal cells and DS cells themselves, and endows DS cells with hair inducing ability. Epidermal homeostasis of pre-existing HFs is disrupted. Additionally, cell-autonomous progressive skin fibrosis is prominent in dermis, where the excessive fibroblasts largely originate from DS. Gene expression analysis of purified DS cells with activated β-catenin revealed significantly increased expression of Bmp, Fgf, and Notch ligands and administration of Bmp, Fgf, or Notch signaling inhibitor attenuates EF formation. In summary, our findings advance the current knowledge of high plasticity of DS cells and provide an insight into understanding how Wnt/β-catenin signaling controls DS cell behaviors.
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Affiliation(s)
- Yixin Tao
- Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Qingchun Yang
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Lei Wang
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Jie Zhang
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Xuming Zhu
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Qianqian Sun
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Yunbin Han
- School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Qian Luo
- School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Yushu Wang
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Xizhi Guo
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Ji Wu
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Baojie Li
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Xiao Yang
- State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, China
| | - Lin He
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
| | - Gang Ma
- Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
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18
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Advances of Stem Cell Therapeutics in Cutaneous Wound Healing and Regeneration. Mediators Inflamm 2017; 2017:5217967. [PMID: 29213192 PMCID: PMC5682068 DOI: 10.1155/2017/5217967] [Citation(s) in RCA: 142] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Revised: 08/14/2017] [Accepted: 09/13/2017] [Indexed: 12/15/2022] Open
Abstract
Cutaneous wound healing is a complex multiple phase process, which overlaps each other, where several growth factors, cytokines, chemokines, and various cells interact in a well-orchestrated manner. However, an imbalance in any of these phases and factors may lead to disruption in harmony of normal wound healing process, resulting in transformation towards chronic nonhealing wounds and abnormal scar formation. Although various therapeutic interventions are available to treat chronic wounds, current wound-care has met with limited success. Progenitor stem cells possess potential therapeutic ability to overcome limitations of the present treatments as it offers accelerated wound repair with tissue regeneration. A substantial number of stem cell therapies for cutaneous wounds are currently under development as a result of encouraging preliminary findings in both preclinical and clinical studies. However, the mechanisms by which these stem cells contribute to the healing process have yet to be elucidated. In this review, we emphasize on the major treatment modalities currently available for the treatment of the wound, role of various interstitial stem cells and exogenous adult stem cells in cutaneous wound healing, and possible mechanisms involved in the healing process.
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19
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Wang Y, Yin P, Bian GL, Huang HY, Shen H, Yang JJ, Yang ZY, Shen ZY. The combination of stem cells and tissue engineering: an advanced strategy for blood vessels regeneration and vascular disease treatment. Stem Cell Res Ther 2017; 8:194. [PMID: 28915929 PMCID: PMC5603030 DOI: 10.1186/s13287-017-0642-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Over the past years, vascular diseases have continued to threaten human health and increase financial burdens worldwide. Transplantation of allogeneic and autologous blood vessels is the most convenient treatment. However, it could not be applied generally due to the scarcity of donors and the patient’s condition. Developments in tissue engineering are contributing greatly with regard to this urgent need for blood vessels. Tissue engineering-derived blood vessels are promising alternatives for patients with aortic dissection/aneurysm. The aim of this review is to show the importance of advances in biomaterials development for the treatment of vascular disease. We also provide a comprehensive overview of the current status of tissue reconstruction from stem cells and transplantable cellular scaffold constructs, focusing on the combination of stem cells and tissue engineering for blood vessel regeneration and vascular disease treatment.
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Affiliation(s)
- Ying Wang
- Department of Cardiovascular Surgery & Institute of Cardiovascular Science, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Pei Yin
- Department of Cardiovascular Surgery & Institute of Cardiovascular Science, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.,Department of Cardio-Thoracic Surgery, Taixing People's Hospital, Taixing, Jiangsu, China
| | - Guang-Liang Bian
- Department of Cardiovascular Surgery & Institute of Cardiovascular Science, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.,Department of Cardio-Thoracic Surgery, Jingjiang People's Hospital, Jingjiang, Jiangsu, China
| | - Hao-Yue Huang
- Department of Cardiovascular Surgery & Institute of Cardiovascular Science, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Han Shen
- Department of Cardiovascular Surgery & Institute of Cardiovascular Science, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jun-Jie Yang
- Department of Cardiovascular Surgery & Institute of Cardiovascular Science, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Zi-Ying Yang
- Department of Cardiovascular Surgery & Institute of Cardiovascular Science, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Zhen-Ya Shen
- Department of Cardiovascular Surgery & Institute of Cardiovascular Science, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
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20
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Improvement of Flap Necrosis in a Rat Random Skin Flap Model by In Vivo Electroporation-Mediated HGF Gene Transfer. Plast Reconstr Surg 2017; 139:1116e-1127e. [PMID: 28445365 DOI: 10.1097/prs.0000000000003259] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Despite great understanding of underlying mechanisms for flap necrosis and advances in surgical techniques, flap necrosis remains a critical issue. In the present study, the authors investigated the efficacy of electroporation-mediated hepatocyte growth factor (HGF) gene delivery to random dorsal skin flaps (McFarlane) to accelerate wound healing and reduce flap necrosis. METHODS Fifteen male Wistar rats (290 to 320 g) were divided randomly into three groups. Group a, the control group (n = 5), underwent surgery and received no gene transfer. Group b received electroporation-mediated HGF gene delivery 24 hours after surgery as a treatment. Group c received electroporation-mediated HGF gene delivery 24 hours before surgery as prophylaxis (n = 5). Planimetry, laser Doppler imaging, and immunohistochemistry were used to assess the efficacy of HGF gene therapy among the groups. RESULTS Electroporation-mediated HGF gene delivery significantly decreased flap necrosis percentage compared with the control group in prophylactic and treatment groups (p = 0.0317 and p = 0.0079, respectively) and significantly increased cutaneous perfusion compared with the control group (p = 0.0317 and p = 0.0159, respectively). Moreover, Spearman rank correlation showed a significant negative correlation between flap necrosis percentage and laser index (p = 0.0213 and r = -0.5964, respectively). Furthermore, significantly higher mean CD31 vessel density was detected in treatment and prophylactic groups (p = 0.0079 and p = 0.0159, respectively). In addition, quantitative image analysis revealed significantly higher HGF protein expression in groups b and c (p = 0.0079 and p = 0.0079, respectively). CONCLUSION These findings suggested in vivo electroporation-mediated HGF gene delivery enhanced viability and vascularity of the ischemic skin flap.
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21
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Seyed Jafari SM, Shafighi M, Beltraminelli H, Weber B, Schmid RA, Geiser T, Gazdhar A, Hunger RE. Efficacy of In Vivo Electroporation-Mediated IL-10 Gene Delivery on Survival of Skin Flaps. J Membr Biol 2017; 251:211-219. [PMID: 28776087 DOI: 10.1007/s00232-017-9974-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 07/29/2017] [Indexed: 12/29/2022]
Abstract
Despite advances in understanding the underlying mechanisms of flap necrosis and improvement in surgical techniques, skin flap necrosis after reconstructive surgery remains a crucial issue. We investigated the efficacy of electroporation-mediated IL-10 gene transfer to random skin flap with an aim to accelerate wound healing and improve skin flap survival. Nine male Wistar rats (300-330 g) were divided in two groups (a) control group (n = 5), only surgery no gene transfer, and (b) experimental group, received electroporation-mediated IL-10 gene transfer 24 h before the surgery as prophylaxis (n = 4). Random skin flap (McFarlane) was performed in both groups. Planimetry, Laser Doppler imaging, and immunohistochemistry were used to evaluate the effect of IL-10 gene transfer between study groups at day 7. Electroporation-mediated IL-10 gene transfer decreased percentage of flap necrosis (p value = 0.0159) and increased cutaneous perfusion compared to the control group (p value = 0.0159). In addition, Spearman's rank correlation showed a significant negative correlation between percentage of flap necrosis and Laser Index (p value = 0.0083, r -0.83, respectively). Furthermore, significantly higher mean CD31+ vessel density was detected in the experimental group compared to the control group (p value = 0.0159). Additionally, semi-quantitative image analysis showed lower inflammatory cell count in experimental group compared to control group (p value = 0.0317). In vivo electroporation-mediated IL-10 gene transfer reduced necrosis, enhanced survival and vascularity in the ischemic skin flap.
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Affiliation(s)
- S Morteza Seyed Jafari
- Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland
- Department of Clinical Research, University of Bern, Bern, Switzerland
- Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
| | - Maziar Shafighi
- Department of Clinical Research, University of Bern, Bern, Switzerland
| | - Helmut Beltraminelli
- Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland
| | - Benedikt Weber
- Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland
| | - Ralph A Schmid
- Department of General Thoracic Surgery, University Hospital, Bern, Switzerland
| | - Thomas Geiser
- Department of Clinical Research, University of Bern, Bern, Switzerland
- Department of Pulmonary Medicine, University Hospital, Inselspital Bern, Bern, Switzerland
| | - Amiq Gazdhar
- Department of Clinical Research, University of Bern, Bern, Switzerland.
- Department of Pulmonary Medicine, University Hospital, Inselspital Bern, Bern, Switzerland.
| | - Robert E Hunger
- Department of Dermatology, Inselspital, Bern University Hospital, Bern, Switzerland
- Department of Clinical Research, University of Bern, Bern, Switzerland
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22
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Lee SE, Uhm SJ, Son YJ, Park YG, Kim EY, Park SP. Intermediate Reprogramming of Mouse Skin Fibroblasts into Stem-Like Cells by Bone Morphogenetic Protein 4. Cell Reprogram 2017; 19:107-115. [PMID: 28170287 DOI: 10.1089/cell.2016.0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Specific transcription factors are sufficient to reprogram fully induced pluripotent stem cells or other types of cells. These findings raise the question of whether chemical molecules or proteins can replace transcription factors to alter the defined cell fate. In this study, we treated mouse skin fibroblasts (MSFs) with bone morphogenetic protein 4 (BMP4) and examined intermediate reprogramming of MSFs into stem-like cells. Putative epidermal stem cells isolated from the ventral skin epidermis of an adult mouse were used to confirm the reprogramming activity of BMP4, which increased the proliferation of these cells. After these cells formed spheroids, they were treated with BMP4 and cultured for 5 days. Following BMP4 treatment, the characteristics of these cells changed, and they expressed Oct-4 and its target transcripts Nanog, Sox2, and alkaline phosphatase. To confirm the stem cell potency of these cells, we induced their differentiation into cardiomyocytes. Stem-like cell-derived cardiomyocytes exhibited mRNA expression of cardiac mesoderm markers such as Nk2 transcription factor-related locus 5 and connexin 40, and the cardiomyocyte marker troponin T. These differentiated cells exhibited contracting masses. These results suggest that BMP4-mediated somatic stem cell reprogramming may become an alternative approach for cell therapy.
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Affiliation(s)
- Seung-Eun Lee
- 1 Stem Cell Research Center, Jeju National University , Jeju, Korea.,2 Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University , Jeju, Korea
| | - Sang-Jun Uhm
- 3 Department of Animal Science and Biotechnology, Sangji Youngseo College , Wonju, South Korea
| | - Yeo-Jin Son
- 1 Stem Cell Research Center, Jeju National University , Jeju, Korea.,2 Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University , Jeju, Korea
| | - Yun-Gwi Park
- 1 Stem Cell Research Center, Jeju National University , Jeju, Korea.,2 Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University , Jeju, Korea
| | - Eun-Young Kim
- 1 Stem Cell Research Center, Jeju National University , Jeju, Korea.,2 Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University , Jeju, Korea.,4 Mirae Cell Bio, Seoul, Korea
| | - Se-Pill Park
- 1 Stem Cell Research Center, Jeju National University , Jeju, Korea.,2 Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University , Jeju, Korea.,4 Mirae Cell Bio, Seoul, Korea
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23
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Ge W, Cheng SF, Dyce PW, De Felici M, Shen W. Skin-derived stem cells as a source of primordial germ cell- and oocyte-like cells. Cell Death Dis 2016; 7:e2471. [PMID: 27831564 PMCID: PMC5260893 DOI: 10.1038/cddis.2016.366] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 08/30/2016] [Accepted: 09/01/2016] [Indexed: 12/19/2022]
Abstract
The skin is a unique organ that contains a variety of stem cells for the maintenance of skin homeostasis and the repair of skin tissues following injury and disease. Skin-derived stem cells (SDSCs) constitute a heterogeneous population of stem cells generated in vitro from dermis, which can be cultured as spherical aggregates of cells in suspension culture. Under certain in vitro or in vivo conditions, SDSCs show multipotency and can generate a variety of neural, mesodermal, and endodermal cell types such as neurons, glia, fibroblasts, adipocytes, muscle cells, chondroblasts, osteoblats, and islet β-cell-like cells. SDSCs are likely derived from multipotent stem cells located in the hair follicles that are, in turn, derived from embryonic migratory neural crest or mesoderm cells. During the past decade, a wave of reports have shown that germ cells can be generated from various types of stem cells. It has been shown that SDSCs are able to produce primordial germ cell-like cells in vitro, and even oocyte-like cells (OLCs). Whether these germ cell-like cells (GCLCs) can give rise to viable progeny remains, however, unknown. In this review, we will discuss the origin and characteristics of SDSCs from which the GCLC are derived, the possible mechanisms of this differentiation process, and finally the prospective biomedical applications of the SDSC-derived GCLCs.
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Affiliation(s)
- Wei Ge
- Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China
| | - Shun-Feng Cheng
- Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China
| | - Paul W Dyce
- Department of Animal Sciences, Auburn University, Auburn, AL 36849, USA
| | - Massimo De Felici
- Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Rome 00133, Italy
| | - Wei Shen
- Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China
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24
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Bai T, Liu F, Zou F, Zhao G, Jiang Y, Liu L, Shi J, Hao D, Zhang Q, Zheng T, Zhang Y, Liu M, Li S, Qi L, Liu JY. Epidermal Growth Factor Induces Proliferation of Hair Follicle-Derived Mesenchymal Stem Cells Through Epidermal Growth Factor Receptor-Mediated Activation of ERK and AKT Signaling Pathways Associated with Upregulation of Cyclin D1 and Downregulation of p16. Stem Cells Dev 2016; 26:113-122. [PMID: 27702388 DOI: 10.1089/scd.2016.0234] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The maintenance of highly proliferative capacity and full differentiation potential is a necessary step in the initiation of stem cell-based regenerative medicine. Our recent study showed that epidermal growth factor (EGF) significantly enhanced hair follicle-derived mesenchymal stem cell (HF-MSC) proliferation while maintaining the multilineage differentiation potentials. However, the underlying mechanism remains unclear. Herein, we investigated the role of EGF in HF-MSC proliferation. HF-MSCs were isolated and cultured with or without EGF. Immunofluorescence staining, flow cytometry, cytochemistry, and western blotting were used to assess proliferation, cell signaling pathways related to the EGF receptor (EGFR), and cell cycle progression. HF-MSCs exhibited surface markers of mesenchymal stem cells and displayed trilineage differentiation potentials toward adipocytes, chondrocytes, and osteoblasts. EGF significantly increased HF-MSC proliferation as well as EGFR, ERK1/2, and AKT phosphorylation (p-EGFR, p-ERK1/2, and p-AKT) in a time- and dose-dependent manner, but not STAT3 phosphorylation. EGFR inhibitor (AG1478), PI3K-AKT inhibitor (LY294002), ERK inhibitor (U0126), and STAT3 inhibitor (STA-21) significantly blocked EGF-induced HF-MSC proliferation. Moreover, AG1478, LY294002, and U0126 significantly decreased p-EGFR, p-AKT, and p-ERK1/2 expression. EGF shifted HF-MSCs at the G1 phase to the S and G2 phase. Concomitantly, cyclinD1, phosphorylated Rb, and E2F1expression increased, while that of p16 decreased. In conclusion, EGF induces HF-MSC proliferation through the EGFR/ERK and AKT pathways, but not through STAT-3. The G1/S transition was stimulated by upregulation of cyclinD1 and inhibition of p16 expression.
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Affiliation(s)
- Tingting Bai
- 1 Department of Pathobiology, Key Laboratory of Ministry of Education, College of Basic Medicine, Jilin University , Changchun, China .,2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China
| | - Feilin Liu
- 2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China .,3 Department of Ophthalmology, Second Hospital of Jilin University , Changchun, China
| | - Fei Zou
- 2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China .,4 Department of Pediatrics, First Hospital of Jilin University , Changchun, China
| | - Guifang Zhao
- 5 Department of Pathology, Jilin Medical College , Jilin, China
| | - Yixu Jiang
- 1 Department of Pathobiology, Key Laboratory of Ministry of Education, College of Basic Medicine, Jilin University , Changchun, China .,2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China
| | - Li Liu
- 1 Department of Pathobiology, Key Laboratory of Ministry of Education, College of Basic Medicine, Jilin University , Changchun, China .,2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China
| | - Jiahong Shi
- 2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China
| | - Deshun Hao
- 1 Department of Pathobiology, Key Laboratory of Ministry of Education, College of Basic Medicine, Jilin University , Changchun, China .,2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China
| | - Qi Zhang
- 2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China
| | - Tong Zheng
- 2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China
| | - Yingyao Zhang
- 2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China
| | - Mingsheng Liu
- 2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China
| | - Shilun Li
- 6 Department of Oncology, First People's Hospital of Lishu County , Lishu County, China
| | - Liangchen Qi
- 7 Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University , Changchun, China
| | - Jin Yu Liu
- 2 Department of Toxicology, School of Public Health, Jilin University , Changchun, China
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Abstract
SUMMARYCells must respond to a diverse, complex, and ever-changing mix of signals, using a fairly limited set of parts. Changes in protein level, protein localization, protein activity, and protein-protein interactions are critical aspects of signal transduction, allowing cells to respond highly specifically to a nearly limitless set of cues and also to vary the sensitivity, duration, and dynamics of the response. Signal-dependent changes in levels of gene expression and protein synthesis play an important role in regulation of protein levels, whereas posttranslational modifications of proteins regulate their degradation, localization, and functional interactions. Protein ubiquitylation, for example, can direct proteins to the proteasome for degradation or provide a signal that regulates their interactions and/or location within the cell. Similarly, protein phosphorylation by specific kinases is a key mechanism for augmenting protein activity and relaying signals to other proteins that possess domains that recognize the phosphorylated residues.
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Affiliation(s)
- Michael J Lee
- David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
| | - Michael B Yaffe
- David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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26
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Toxic Epidermal Necrolysis in Recessive Dystrophic Epidermolysis Bullosa following Bone Marrow Transplantation. J Pediatr 2016; 173:242-4. [PMID: 26976809 PMCID: PMC5322426 DOI: 10.1016/j.jpeds.2016.02.037] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 01/12/2016] [Accepted: 02/10/2016] [Indexed: 01/21/2023]
Abstract
A 3-year-old child with recessive dystrophic epidermolysis bullosa treated with bone marrow transplantation subsequently developed body-wide epidermal detachment distinct from his epidermolysis bullosa. Toxic epidermal necrolysis was diagnosed by examination and skin biopsy. Although graft-vs-host disease was considered, he had no features of this diagnosis by laboratory studies or skin biopsy, and he improved without addition of further immune suppressants. Throughout the episode, the patient was maintained on cyclosporine A, a component of his transplant regimen, and also a reported therapy for toxic epidermal necrolysis. He had full recovery. Re-epithelialization occurred in a unique folliculocentric pattern, which we postulate was related to the patient's mesenchymal stem cell infusion, received as an adjunct to his marrow transplantation.
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27
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Mitchell A, Wei P, Lim WA. Oscillatory stress stimulation uncovers an Achilles' heel of the yeast MAPK signaling network. Science 2015; 350:1379-83. [PMID: 26586187 DOI: 10.1126/science.aab0892] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Accepted: 11/08/2015] [Indexed: 01/26/2023]
Abstract
Cells must interpret environmental information that often changes over time. In our experiment, we systematically monitored the growth of yeast cells under various frequencies of oscillating osmotic stress. Growth was severely inhibited at a particular resonance frequency, at which cells show hyperactivated transcriptional stress responses. This behavior represents a sensory misperception: The cells incorrectly interpret oscillations as a staircase of ever-increasing osmolarity. The misperception results from the capacity of the osmolarity-sensing mitogen-activated protein kinase (MAPK) network to retrigger with sequential osmotic stresses. Although this feature is critical for coping with natural challenges, such as continually increasing osmolarity, it results in a trade-off of fragility to non-natural oscillatory inputs that match the retriggering time. These findings demonstrate the value of non-natural dynamic perturbations in exposing hidden sensitivities of cellular regulatory networks.
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Affiliation(s)
- Amir Mitchell
- Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA. Center for Systems and Synthetic Biology, UCSF, San Francisco, CA 94158, USA
| | - Ping Wei
- Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA. Center for Quantitative Biology, and Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Peking University, Beijing 100871, China.
| | - Wendell A Lim
- Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA. Center for Systems and Synthetic Biology, UCSF, San Francisco, CA 94158, USA. Howard Hughes Medical Institute (HHMI), UCSF, San Francisco, CA 94158, USA.
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28
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Ojeh N, Pastar I, Tomic-Canic M, Stojadinovic O. Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications. Int J Mol Sci 2015; 16:25476-501. [PMID: 26512657 PMCID: PMC4632811 DOI: 10.3390/ijms161025476] [Citation(s) in RCA: 190] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 10/15/2015] [Accepted: 10/20/2015] [Indexed: 12/18/2022] Open
Abstract
The skin is the largest organ of the body and has an array of functions. Skin compartments, epidermis, and hair follicles house stem cells that are indispensable for skin homeostasis and regeneration. These stem cells also contribute to wound repair, resulting in restoration of tissue integrity and function of damaged tissue. Unsuccessful wound healing processes often lead to non-healing wounds. Chronic wounds are caused by depletion of stem cells and a variety of other cellular and molecular mechanisms, many of which are still poorly understood. Current chronic wound therapies are limited, so the search to develop better therapeutic strategies is ongoing. Adult stem cells are gaining recognition as potential candidates for numerous skin pathologies. In this review, we will discuss epidermal and other stem cells present in the skin, and highlight some of the therapeutic applications of epidermal stem cells and other adult stem cells as tools for cell/scaffold-based therapies for non-healing wounds and other skin disorders. We will also discuss emerging concepts and offer some perspectives on how skin tissue-engineered products can be optimized to provide efficacious therapy in cutaneous repair and regeneration.
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Affiliation(s)
- Nkemcho Ojeh
- Faculty of Medical Sciences, the University of the West Indies, Cave Hill Campus, P.O. Box 64, Bridgetown BB 11000, St. Michael, Barbados; E-Mail:
| | - Irena Pastar
- Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami Miller Medical School, 1600 NW 10th Avenue, RMSB, Room 2023-A, Miami, FL 33136, USA; E-Mails: (I.P.); (M.T.-C.)
| | - Marjana Tomic-Canic
- Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami Miller Medical School, 1600 NW 10th Avenue, RMSB, Room 2023-A, Miami, FL 33136, USA; E-Mails: (I.P.); (M.T.-C.)
| | - Olivera Stojadinovic
- Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami Miller Medical School, 1600 NW 10th Avenue, RMSB, Room 2023-A, Miami, FL 33136, USA; E-Mails: (I.P.); (M.T.-C.)
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +1-305-243-7295; Fax: +1-305-243-6191
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Sehic A, Utheim ØA, Ommundsen K, Utheim TP. Pre-Clinical Cell-Based Therapy for Limbal Stem Cell Deficiency. J Funct Biomater 2015; 6:863-88. [PMID: 26343740 PMCID: PMC4598682 DOI: 10.3390/jfb6030863] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 08/10/2015] [Accepted: 08/21/2015] [Indexed: 12/13/2022] Open
Abstract
The cornea is essential for normal vision by maintaining transparency for light transmission. Limbal stem cells, which reside in the corneal periphery, contribute to the homeostasis of the corneal epithelium. Any damage or disease affecting the function of these cells may result in limbal stem cell deficiency (LSCD). The condition may result in both severe pain and blindness. Transplantation of ex vivo cultured cells onto the cornea is most often an effective therapeutic strategy for LSCD. The use of ex vivo cultured limbal epithelial cells (LEC), oral mucosal epithelial cells, and conjunctival epithelial cells to treat LSCD has been explored in humans. The present review focuses on the current state of knowledge of the many other cell-based therapies of LSCD that have so far exclusively been explored in animal models as there is currently no consensus on the best cell type for treating LSCD. Major findings of all these studies with special emphasis on substrates for culture and transplantation are systematically presented and discussed. Among the many potential cell types that still have not been used clinically, we conclude that two easily accessible autologous sources, epidermal stem cells and hair follicle-derived stem cells, are particularly strong candidates for future clinical trials.
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Affiliation(s)
- Amer Sehic
- Department of Oral Biology, Faculty of Dentistry, University of Oslo, Sognsvannsveien 10, Oslo 0372, Norway.
| | - Øygunn Aass Utheim
- Department of Ophthalmology, Oslo University Hospital, Kirkeveien 166, Oslo 0407, Norway.
| | - Kristoffer Ommundsen
- Department of Medical Biochemistry, Oslo University Hospital, Kirkeveien 166, Oslo 0407, Norway.
| | - Tor Paaske Utheim
- Department of Oral Biology, Faculty of Dentistry, University of Oslo, Sognsvannsveien 10, Oslo 0372, Norway.
- Department of Medical Biochemistry, Oslo University Hospital, Kirkeveien 166, Oslo 0407, Norway.
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30
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Vapniarsky N, Arzi B, Hu JC, Nolta JA, Athanasiou KA. Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine. Stem Cells Transl Med 2015; 4:1187-98. [PMID: 26253713 DOI: 10.5966/sctm.2015-0084] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Accepted: 07/08/2015] [Indexed: 12/16/2022] Open
Abstract
UNLABELLED The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. SIGNIFICANCE Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides analysis of the current state-of-the-art regenerative approaches using human-derived dermal stem cells, with consideration of current guidelines, to assist translation toward therapeutic use.
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Affiliation(s)
- Natalia Vapniarsky
- Department of Biomedical Engineering, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, Institute for Regenerative Cures and Department of Internal Medicine, School of Medicine, and Department of Orthopaedic Surgery, University of California, Davis, Davis, California, USA
| | - Boaz Arzi
- Department of Biomedical Engineering, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, Institute for Regenerative Cures and Department of Internal Medicine, School of Medicine, and Department of Orthopaedic Surgery, University of California, Davis, Davis, California, USA
| | - Jerry C Hu
- Department of Biomedical Engineering, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, Institute for Regenerative Cures and Department of Internal Medicine, School of Medicine, and Department of Orthopaedic Surgery, University of California, Davis, Davis, California, USA
| | - Jan A Nolta
- Department of Biomedical Engineering, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, Institute for Regenerative Cures and Department of Internal Medicine, School of Medicine, and Department of Orthopaedic Surgery, University of California, Davis, Davis, California, USA
| | - Kyriacos A Athanasiou
- Department of Biomedical Engineering, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, Institute for Regenerative Cures and Department of Internal Medicine, School of Medicine, and Department of Orthopaedic Surgery, University of California, Davis, Davis, California, USA
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31
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Ma D, Kua JEH, Lim WK, Lee ST, Chua AWC. In vitro characterization of human hair follicle dermal sheath mesenchymal stromal cells and their potential in enhancing diabetic wound healing. Cytotherapy 2015; 17:1036-51. [DOI: 10.1016/j.jcyt.2015.04.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Revised: 04/01/2015] [Accepted: 04/02/2015] [Indexed: 01/09/2023]
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32
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Li P, Liu F, Wu C, Jiang W, Zhao G, Liu L, Bai T, Wang L, Jiang Y, Guo L, Qi X, Kou J, Fan R, Hao D, Lan S, Li Y, Liu JY. Feasibility of human hair follicle-derived mesenchymal stem cells/CultiSpher(®)-G constructs in regenerative medicine. Cell Tissue Res 2015; 362:69-86. [PMID: 25948482 DOI: 10.1007/s00441-015-2182-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 03/25/2015] [Indexed: 12/30/2022]
Abstract
The use of human mesenchymal stem cells (hMSCs) in cell therapies has increased the demand for strategies that allow efficient cell scale-up. Preliminary data on the three-dimensional (3D) spinner culture describing the potential use of microcarriers for hMSCs culture scale-up have been reported. We exploited a rich source of autologous stem cells (human hair follicle) and demonstrated the robust in vitro long-term expansion of human hair follicle-derived mesenchymal stem cells (hHF-MSCs) by using CultiSpher(®)-G microcarriers. We analyzed the feasibility of 3D culture by using hHF-MSCs/CultiSpher(®)-G microcarrier constructs for its potential applicability in regenerative medicine by comparatively analyzing the performance of hHF-MSCs adhered to the CultiSpher(®)-G microspheres in 3D spinner culture and those grown on the gelatin-coated plastic dishes (2D culture), using various assays. We showed that the hHF-MSCs seeded at various densities quickly adhered to and proliferated well on the microspheres, thus generating at least hundreds of millions of hHF-MSCs on 1 g of CultiSpher(®)-G within 12 days. This resulted in a cumulative cell expansion of greater than 26-fold. Notably, the maximum and average proliferation rates in 3D culture were significantly greater than that of the 2D culture. However, the hHF-MSCs from both the cultures retained surface marker and nestin expression, proliferation capacity and differentiation potentials toward adipocytes, osteoblasts and smooth muscle cells and showed no significant differences as evidenced by Edu incorporation, cell cycle, colony formation, apoptosis, biochemical quantification and qPCR assays.
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Affiliation(s)
- Pengdong Li
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China.,Department of Toxicology, School of Preventive Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Feilin Liu
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Chunling Wu
- Harbin Veterinary Research Institute, CAAS-Michigan State University Joint Laboratory of Innate Immunity, State Key Laboratory of Veterinary Biotechnology, Chinese Academy of Agricultural Sciences, Maduan Street 427, Nangang District, Harbin, 150001, People's Republic of China
| | - Wenyue Jiang
- Department of Analytical Chemistry, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Guifang Zhao
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Li Liu
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Tingting Bai
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Li Wang
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Yixu Jiang
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Lili Guo
- Department of Pathology, Jilin Cancer Hospital, Changchun, Jilin, 130012, People's Republic of China
| | - Xiaojuan Qi
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Junna Kou
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Ruirui Fan
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Deshun Hao
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Shaowei Lan
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Yulin Li
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China
| | - Jin Yu Liu
- Department of Pathobiology, Key Laboratory of Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China. .,Department of Toxicology, School of Preventive Medicine, Jilin University, Changchun, Jilin, 130021, People's Republic of China.
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Son S, Liang MS, Lei P, Xue X, Furlani EP, Andreadis ST. Magnetofection Mediated Transient NANOG Overexpression Enhances Proliferation and Myogenic Differentiation of Human Hair Follicle Derived Mesenchymal Stem Cells. Bioconjug Chem 2015; 26:1314-27. [PMID: 25685943 DOI: 10.1021/bc5005203] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
We used magnetofection (MF) to achieve high transfection efficiency into human mesenchymal stem cells (MSCs). A custom-made magnet array, matching well-to-well to a 24-well plate, was generated and characterized. Theoretical predictions of magnetic force distribution within each well demonstrated that there was no magnetic field interference among magnets in adjacent wells. An optimized protocol for efficient gene delivery to human hair follicle derived MSCs (hHF-MSCs) was established using an egfp-encoding plasmid, reaching approximately ∼50% transfection efficiency without significant cytotoxicity. Then we applied the optimized MF protocol to express the pluripotency-associated transcription factor NANOG, which was previously shown to reverse the effects of organismal aging on MSC proliferation and myogenic differentiation capacity. Indeed, MF-mediated NANOG delivery increased proliferation and enhanced the differentiation of hHF-MSCs into smooth muscle cells (SMCs). Collectively, our results show that MF can achieve high levels of gene delivery to MSCs and, therefore, may be employed to moderate or reverse the effects of cellular senescence or reprogram cells to the pluripotent state without permanent genetic modification.
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Affiliation(s)
| | | | | | | | | | - Stelios T Andreadis
- ∥Center of Excellence in Bioinformatics and Life Sciences, Buffalo, New York 14203, United States
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Transdifferentiation of Human Hair Follicle Mesenchymal Stem Cells into Red Blood Cells by OCT4. Stem Cells Int 2015; 2015:389628. [PMID: 25755671 PMCID: PMC4337757 DOI: 10.1155/2015/389628] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 01/09/2015] [Accepted: 01/12/2015] [Indexed: 12/30/2022] Open
Abstract
Shortage of red blood cells (RBCs, erythrocytes) can have potentially life-threatening consequences for rare or unusual blood type patients with massive blood loss resulting from various conditions. Erythrocytes have been derived from human pluripotent stem cells (PSCs), but the risk of potential tumorigenicity cannot be ignored, and a majority of these cells produced from PSCs express embryonic ε- and fetal γ-globins with little or no adult β-globin and remain nucleated. Here we report a method to generate erythrocytes from human hair follicle mesenchymal stem cells (hHFMSCs) by enforcing OCT4 gene expression and cytokine stimulation. Cells generated from hHFMSCs expressed mainly the adult β-globin chain with minimum level of the fetal γ-globin chain. Furthermore, these cells also underwent multiple maturation events and formed enucleated erythrocytes with a biconcave disc shape. Gene expression analyses showed that OCT4 regulated the expression of genes associated with both pluripotency and erythroid development during hHFMSC transdifferentiation toward erythroid cells. These findings show that mature erythrocytes can be generated from adult somatic cells, which may serve as an alternative source of RBCs for potential autologous transfusion.
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35
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Hsia CW, Ho MY, Shui HA, Tsai CB, Tseng MJ. Analysis of dermal papilla cell interactome using STRING database to profile the ex vivo hair growth inhibition effect of a vinca alkaloid drug, colchicine. Int J Mol Sci 2015; 16:3579-98. [PMID: 25664862 PMCID: PMC4346914 DOI: 10.3390/ijms16023579] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Accepted: 01/03/2015] [Indexed: 12/28/2022] Open
Abstract
Dermal papillae (DPs) control the formation of hair shafts. In clinical settings, colchicine (CLC) induces patients' hair shedding. Compared to the control, the ex vivo hair fiber elongation of organ cultured vibrissa hair follicles (HFs) declined significantly after seven days of CLC treatment. The cultured DP cells (DPCs) were used as the experimental model to study the influence of CLC on the protein dynamics of DPs. CLC could alter the morphology and down-regulate the expression of alkaline phosphatase (ALP), the marker of DPC activity, and induce IκBα phosphorylation of DPCs. The proteomic results showed that CLC modulated the expression patterns (fold>2) of 24 identified proteins, seven down-regulated and 17 up-regulated. Most of these proteins were presumably associated with protein turnover, metabolism, structure and signal transduction. Protein-protein interactions (PPI) among these proteins, established by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, revealed that they participate in protein metabolic process, translation, and energy production. Furthermore, ubiquitin C (UbC) was predicted to be the controlling hub, suggesting the involvement of ubiquitin-proteasome system in modulating the pathogenic effect of CLC on DPC.
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Affiliation(s)
- Ching-Wu Hsia
- Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chia-yi 621, Taiwan.
| | - Ming-Yi Ho
- Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
| | - Hao-Ai Shui
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.
| | - Chong-Bin Tsai
- Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chia-yi 621, Taiwan.
- Department of Ophthalmology, Chia-yi Christian Hospital, Chia-yi 600, Taiwan.
| | - Min-Jen Tseng
- Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chia-yi 621, Taiwan.
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Gao Y, Liu F, Zhang L, Su X, Liu JY, Li Y. Acellular blood vessels combined human hair follicle mesenchymal stem cells for engineering of functional arterial grafts. Ann Biomed Eng 2014; 42:2177-89. [PMID: 25023659 DOI: 10.1007/s10439-014-1061-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Accepted: 06/19/2014] [Indexed: 12/11/2022]
Abstract
Tissue-engineered vessels offer options for autologous vascular grafts in cardiovascular repair and regeneration. The experiments aimed to construct functional arterial grafts by combining human hair follicle mesenchymal stem cells (HF-MSCs) with acellular umbilical arteries. We isolated mesenchymal stem cells from human hair follicles. Under appropriate culture conditions, these cells displayed CD44, CD90 and CD105, and exhibited the potential for differentiation to adipocytes, osteoblasts and chondrocytes. Very promisingly, HF-MSCs expressed the vascular smooth muscle specific markers in the presence of transforming growth factor-β. We created acellular arterial scaffolds by digesting human umbilical arteries with trypsin and sodium dodecyl sulfate. These acellular arterial scaffolds retained major components of the extracellular matrix. The mechanical properties of these acellular arterial scaffolds were very similar to those of native blood vessels. We then seeded HF-MSCs into acellular arterial scaffolds and found that they still expressed vascular smooth muscle specific markers. The arterial grafts derived from HF-MSCs demonstrated vasoreactivity in response to humoral constrictors. We constructed arterial grafts that are very close to native blood vessels in their structures and physiological functions. These properties suggest that these arterial grafts could be used as small diameter arterial grafts for cardiovascular repair and regeneration.
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Affiliation(s)
- Yunhe Gao
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, 130021, Jilin, China
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Chen Z, Wang Y, Shi C. Therapeutic Implications of Newly Identified Stem Cell Populations From the Skin Dermis. Cell Transplant 2014; 24:1405-22. [PMID: 24972091 DOI: 10.3727/096368914x682431] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Skin, the largest organ of the body, is a promising reservoir for adult stem cells. The epidermal stem cells and hair follicle stem cells have been well studied for their important roles in homeostasis, regeneration, and repair of the epidermis and appendages for decades. However, stem cells residing in dermis were not identified until the year 2001, when a variety of stem cell subpopulations have been isolated and identified from the dermis of mammalian skin such as neural crest stem cells, mesenchymal stem cell-like dermal stem cells, and dermal hematopoietic cells. These stem cell subpopulations exhibited capabilities of self-renewing, multipotent differentiating, and immunosuppressive properties. Hence, the dermis-derived stem cells showed extensive potential applications in regenerative medicine, especially for wound healing/tissue repair, neural repair, and hematopoietic recovery. Here we summarized current research on the stem cell subpopulations derived from the dermis and aimed to provide a comprehensive review on their isolation, specific markers, differentiation capacity, and the functional activities in homeostasis, regeneration, and tissue repair.
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Affiliation(s)
- Zelin Chen
- Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
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Bertolini M, Meyer KC, Slominski R, Kobayashi K, Ludwig RJ, Paus R. The immune system of mouse vibrissae follicles: cellular composition and indications of immune privilege. Exp Dermatol 2014; 22:593-8. [PMID: 23947674 DOI: 10.1111/exd.12205] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2013] [Indexed: 12/22/2022]
Abstract
Although vibrissae hair follicles (VHFs) have long been a key research model in the life sciences, their immune system (IS) is essentially unknown. Therefore, we have characterized basic parameters of the VHF-IS of C57BL/6J mice by quantitative (immuno-)histomorphometry. Murine anagen VHF harbour few CD4+ and CD8+ T cells in the distal mesenchyme and sinuses but hardly any gamma-delta T cells in their distal epithelium. MHC class II+ Langerhans cells are seeded in the VHF infundibulum, which is also surrounded by MHC class II+ and CD11b+ cells (macrophages). The number of Langerhans cells then declines sharply in the VHF bulge, and the VHF bulb lacks MHC class II+ cells. Mast cells densely populate the VHF connective tissue sheath, where they strikingly cluster around the bulge. Both the bulge and the bulb of VHF display signs of immune privilege, that is, low MHC class I and MHC class II expression and local immunoinhibitor expression (CD200, TGFβ1). This immunophenotyping study fills an important gap in the immunobiology of murine skin and identifies differences between the IS of VHF, mouse pelage and human terminal HFs. This facilitates utilizing murine VHF as a versatile organ culture model for general immunology and immune privilege research in situ.
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Affiliation(s)
- Marta Bertolini
- Department of Dermatology, University of Lübeck, Lübeck, Germany
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39
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Yu M, Finner A, Shapiro J, Lo B, Barekatain A, McElwee KJ. Hair follicles and their role in skin health. ACTA ACUST UNITED AC 2014. [DOI: 10.1586/17469872.1.6.855] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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40
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Hodgkinson T, Yuan XF, Bayat A. Adult stem cells in tissue engineering. Expert Rev Med Devices 2014; 6:621-40. [DOI: 10.1586/erd.09.48] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Hong S, Alapure BV, Lu Y, Tian H, Wang Q. Immunohistological localization of endogenous unlabeled stem cells in wounded skin. J Histochem Cytochem 2014; 62:276-85. [PMID: 24399040 DOI: 10.1369/0022155414520710] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Various types of endogenous stem cells (SCs) participate in wound healing in the skin at different anatomical locations. SCs need to be identified through multiple markers, and this is usually performed using flow cytometry. However, immunohistological identification of endogenous stem cells in the skin at different anatomical locations by co-staining multiple SC markers has been seldom explored. We examined the immunohistological localization of four major types of SCs in wounded skin by co-staining for their multiple markers. Hematopoietic SCs were co-stained for Sca1 and CD45; mesenchymal SCs for Sca1, CD29, and CD106; adipose SCs for CD34, CD90, and CD105; and endothelial progenitor cells and their differentiated counterparts were co-stained for CD34, Tie2, and von Willebrand factor. We found Sca1(+)CD45(+) SCs in the epidermis, dermis and hypodermis of wounded skin. Sca1(+)CD29(+) and Sca1(+)CD106(+) mesenchymal SCs, CD34(+)CD105(+), CD34(+)CD90(+), and CD90(+)CD105(+) adipose SCs, as well as CD34(+)Tie2(+) endothelial progenitor cells were also located in the epidermis, dermis, and hypodermis. This study demonstrates the feasibility of using immunohistological staining to determine the location of SCs in wounded skin and the intracellular distribution of their molecular markers.
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Affiliation(s)
- Song Hong
- Center of Neuroscience Excellence, Louisiana State University Health Science Center, New Orleans, Louisiana
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42
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Mistriotis P, Andreadis ST. Hair follicle: a novel source of multipotent stem cells for tissue engineering and regenerative medicine. TISSUE ENGINEERING PART B-REVIEWS 2013; 19:265-78. [PMID: 23157470 DOI: 10.1089/ten.teb.2012.0422] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The adult body harbors powerful reservoirs of stem cells that enable tissue regeneration under homeostatic conditions or in response to disease or injury. The hair follicle (HF) is a readily accessible mini organ within the skin and contains stem cells from diverse developmental origins that were shown to have surprisingly broad differentiation potential. In this review, we discuss the biology of the HF with particular emphasis on the various stem cell populations residing within the tissue. We summarize the existing knowledge on putative HF stem cell markers, the differentiation potential, and technologies to isolate and expand distinct stem cell populations. We also discuss the potential of HF stem cells for drug and gene delivery, tissue engineering, and regenerative medicine. We propose that the abundance of stem cells with broad differentiation potential and the ease of accessibility makes the HF an ideal source of stem cells for gene and cell therapies.
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Affiliation(s)
- Panagiotis Mistriotis
- Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York 14260-4200, USA
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43
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Gledhill K, Gardner A, Jahoda CAB. Isolation and establishment of hair follicle dermal papilla cell cultures. Methods Mol Biol 2013; 989:285-292. [PMID: 23483403 DOI: 10.1007/978-1-62703-330-5_22] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
The isolation of hair follicle dermal papilla cells has become an important technique in the field of cutaneous stem cell biology. These cells can be used for a number of biological and translational purposes. They are studied to identify the cellular characteristics and molecular factors that underpin the initiation, maintenance, and modulation of hair growth; to develop new human hair replacement techniques; and as a source of cells capable of being directed down a variety of different lineages. Here, we describe the isolation of hair follicle dermal papilla cells from both human and murine sources via the microdissection techniques used in our lab.
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Affiliation(s)
- Karl Gledhill
- School of Biological and Biomedical Sciences, Durham University, Durham, UK
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Ceafalan L, Gherghiceanu M, Popescu LM, Simionescu O. Telocytes in human skin--are they involved in skin regeneration? J Cell Mol Med 2012; 16:1405-20. [PMID: 22500885 PMCID: PMC3823211 DOI: 10.1111/j.1582-4934.2012.01580.x] [Citation(s) in RCA: 152] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Telocytes (TCs), a particular interstitial cell type, have been recently described in a wide variety of mammalian organs (www.telocytes.com). The TCs are identified morphologically by a small cell body and extremely long (tens to hundreds of μm), thin prolongations (less than 100 nm in diameter, below the resolving power of light microscopy) called telopodes. Here, we demonstrated with electron microscopy and immunofluorescence that TCs were present in human dermis. In particular, TCs were found in the reticular dermis, around blood vessels, in the perifollicular sheath, outside the glassy membrane and surrounding sebaceous glands, arrector pili muscles and both the secretory and excretory portions of eccrine sweat glands. Immunofluorescence screening and laser scanning confocal microscopy showed two subpopulations of dermal TCs; one expressed c-kit/CD117 and the other was positive for CD34. Both subpopulations were also positive for vimentin. The TCs were connected to each other by homocellular junctions, and they formed an interstitial 3D network. We also found TCs adjoined to stem cells in the bulge region of hair follicles. Moreover, TCs established atypical heterocellular junctions with stem cells (clusters of undifferentiated cells). Given the frequency of allergic skin pathologies, we would like to emphasize the finding that close, planar junctions were frequently observed between TCs and mast cells. In conclusion, based on TC distribution and intercellular connections, our results suggested that TCs might be involved in skin homeostasis, skin remodelling, skin regeneration and skin repair.
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Affiliation(s)
- Laura Ceafalan
- Molecular Medicine Laboratory, V. Babeş National Institute of Pathology, Bucharest, Romania
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Abstract
Acute ischemic stroke causes a disturbance of neuronal circuitry and disruption of the blood-brain barrier that can lead to functional disabilities. At present, thrombolytic therapy inducing recanalization of the occluded vessels in the cerebral infarcted area is a commonly used therapeutic strategy. However, only a minority of patients have timely access to this kind of therapy. Recently, neural stem cells (NSCs) as therapy for stroke have been developed in preclinical studies. NSCs are harbored in the subventricular zone (SVZ) as well as the subgranular zone of the brain. The microenvironment in the SVZ, including intercellular interactions, extracellular matrix proteins, and soluble factors, can promote NSC proliferation, self-renewal, and multipotency. Endogenous neurogenesis responds to insults of ischemic stroke supporting the existence of remarkable plasticity in the mammalian brain. Homing and integration of NSCs to the sites of damaged brain tissue are complex morphological and physiological processes. This review provides an update on current preclinical cell therapies for stroke, focusing on neurogenesis in the SVZ and dentate gyrus and on recruitment cues that promote NSC homing and integration to the site of the damaged brain.
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Affiliation(s)
- Dah-Ching Ding
- Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan, ROC
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Stenn K, Parimoo S, Zheng Y, Barrows T, Boucher M, Washenik K. Bioengineering the hair follicle. Organogenesis 2012; 3:6-13. [PMID: 19279694 DOI: 10.4161/org.3.1.3237] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The hair follicle develops from the primitive embryonic epidermis as a result of complex epithelial-mesenchymal interactions. The full follicle, consisting of epithelial cylinders under control of a proximal lying mesenchymal papilla, grows in cycles giving rise to a new hair shaft during each cycle. The ability to cycle endows the follicle with regenerative properties. The evolution of hair follicle engineering began with the recognition in the early 1960's that hair follicles could be transplanted clinically into a foreign site and still grow a shaft typical of the donor site. Since that time, it has been found that the follicular papilla has hair follicle inducing properties and that the hair follicle houses within it epithelial stem cells that can respond to hair inductive signals. These findings have laid the foundation for isolating hair-forming cells, for expanding the cells in culture, and for forming new follicles in vivo.
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Affiliation(s)
- K Stenn
- Aderans Research Institute, Inc.; Philadelphia, Pennsylvania USA
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Abstract
Urinary diversion after radical cystectomy in patients with bladder cancer normally takes the form of an ileal conduit or neobladder. However, such diversions are associated with a number of complications including increased risk of infection. A plausible alternative is the construction of a neobladder (or bladder tissue) in vitro using autologous cells harvested from the patient. Biomaterials can be used as a scaffold for naturally occurring regenerative stem cells to latch onto to regrow the bladder smooth muscle and epithelium. Such engineered tissues show great promise in urologic tissue regeneration, but are faced with a number of challenges. For example, the differentiation mesenchymal stem cells from various sources can be difficult and the smooth muscle cells formed do not precisely mimic the natural cells.
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Bajpai VK, Andreadis ST. Stem cell sources for vascular tissue engineering and regeneration. TISSUE ENGINEERING PART B-REVIEWS 2012; 18:405-25. [PMID: 22571595 DOI: 10.1089/ten.teb.2011.0264] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
This review focuses on the stem cell sources with the potential to be used in vascular tissue engineering and to promote vascular regeneration. The first clinical studies using tissue-engineered vascular grafts are already under way, supporting the potential of this technology in the treatment of cardiovascular and other diseases. Despite progress in engineering biomaterials with the appropriate mechanical properties and biological cues as well as bioreactors for generating the correct tissue microenvironment, the source of cells that make up the vascular tissues remains a major challenge for tissue engineers and physicians. Mature cells from the tissue of origin may be difficult to obtain and suffer from limited proliferative capacity, which may further decline as a function of donor age. On the other hand, multipotent and pluripotent stem cells have great potential to provide large numbers of autologous cells with a great differentiation capacity. Here, we discuss the adult multipotent as well as embryonic and induced pluripotent stem cells, their differentiation potential toward vascular lineages, and their use in engineering functional and implantable vascular tissues. We also discuss the associated challenges that need to be addressed in order to facilitate the transition of this technology from the bench to the bedside.
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Affiliation(s)
- Vivek K Bajpai
- Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York 14260-4200, USA
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Bell E, Richardson GD, Jahoda CA, Gledhill K, Phillips HM, Henderson D, Owens WA, Hole N. Dermal stem cells can differentiate down an endothelial lineage. Stem Cells Dev 2012; 21:3019-30. [PMID: 22571645 DOI: 10.1089/scd.2011.0694] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
In this study, we have demonstrated that cells of neural crest origin located in the dermal papilla (DP) exhibit endothelial marker expression and a functional activity. When grown in endothelial growth media, DP primary cultures upregulate expression of vascular endothelial growth factor receptor 1 (FLT1) mRNA and downregulate expression of the dermal stem cell marker α-smooth muscle actin. DP cells have demonstrated functional characteristics of endothelial cells, including the ability to form capillary-like structures on Matrigel, increase uptake of low-density lipoprotein and upregulate ICAM1 (CD54) in response to tumour necrosis factor alpha (TNF-α) stimulation. We confirmed that these observations were not due to contaminating endothelial cells, by using DP clones. We have also used the WNT1cre/ROSA26R and WNT1cre/YFP lineage-tracing mouse models to identify a population of neural crest-derived cells in DP cultures that express the endothelial marker PECAM (CD31); these cells also form capillary-like structures on Matrigel. Importantly, cells of neural crest origin that express markers of endothelial and mesenchymal lineages exist within the dermal sheath of the vibrissae follicle.
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Affiliation(s)
- Emma Bell
- School of Biological and Biomedical Sciences, Durham University, Durham, UK
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50
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Saichanma S, Bunyaratvej A, Sila-Asna M. In vitro transdifferentiation of corneal epithelial-like cells from human skin-derived precursor cells. Int J Ophthalmol 2012; 5:158-63. [PMID: 22762041 DOI: 10.3980/j.issn.2222-3959.2012.02.08] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2011] [Accepted: 03/15/2012] [Indexed: 12/28/2022] Open
Abstract
The damage of human corneal cells encounter with the problem of availability of corneal cells for replacement. Limitation of the source of corneal cells has been realized. An attempt of development of corneal epithelial-like cells from the human skin-derived precursor (hSKPs) has been made in this study. Combination of three essential growth factors: epidermal growth factor (EGF), keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) could demonstrate successfully induction of hSKPs to differentiation into corneal cells.The induced cells expressed the appearance of markers of corneal epithelial cells as shown by the presence of keratin 3 (K3) by antibody label and Western blot assay. The K3 gene expression of induced hSKPs cells as shown by reverse transcription-polymerase chain reaction (RT-PCR) technology was also demonstrated. The presence of these markers at both gene and protein levels could lead to our conclusion that the directional transdifferentiation of hSKPs cells into corneal epithelial cells was successfully done under this cell induction protocol. The finding shows a newly available stem cell source can be obtained from easily available skin. Cells from autologous human skin might be used for corneal disorder treatment in future clinical application.
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Affiliation(s)
- Sarawut Saichanma
- Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 14140, Thailand
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