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Xu L, Gao W, Bai S, Duan H, Pan X, Wu W. MEF/KSF-conditioned culture medium: An effective method for in vitro culture of mouse dermal papilla cells with osteogenic differentiation potential. Exp Ther Med 2021; 22:828. [PMID: 34149874 PMCID: PMC8200806 DOI: 10.3892/etm.2021.10260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 01/08/2021] [Indexed: 11/06/2022] Open
Abstract
Hair follicle stem cells are pluripotent and have a self-renewal capacity and multi-differentiation potential in vitro. As hair follicle stem cells can be easily sampled from the skin and hair of clinical patients at a considerable quantity, these cells have potential applications in wound repair and skin tissue engineering. Effective approaches for the in vitro culture and amplification of mouse hair follicle stem cells, as well as the in vitro osteogenic differentiation potential and cell source when obtaining mouse-separated cells were examined. Serial subculture was performed in different culture systems. Cell source was detected based on the relevant surface markers derived from mouse hair follicles at the gene and protein levels, and the differential potential was determined. The proliferative ability of hair follicle-derived stem cells obtained from mouse embryonic fibroblast (MEF)/keratinocyte serum-free medium (KSF)-conditioned medium was the highest among all culture systems. The induced group had a stronger osteogenic differentiation potential compared with the non-induced group, indicating that the cells obtained from MEF/KSF-conditioned medium were cells derived from the hair follicle dermal papilla. Therefore, the strong osteogenic differentiation potential of the hair follicle-derived mesenchymal stem cells was screened with MEF/KSF-conditioned culture medium following amplification, and biological characteristics similar to those of hair follicle dermal papilla cells were observed.
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Affiliation(s)
- Liang Xu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
| | - Wenlan Gao
- Department of Stomatology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
| | - Shanshan Bai
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
| | - Huichuan Duan
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
| | - Xiaogang Pan
- Department of Orthodontics, Shanghai Ninth Peoples' Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
| | - Wei Wu
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
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Shao S, Fang H, Li Q, Wang G. Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment. Am J Cancer Res 2020; 10:9937-9955. [PMID: 32929326 PMCID: PMC7481415 DOI: 10.7150/thno.45488] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 07/31/2020] [Indexed: 12/16/2022] Open
Abstract
Extracellular vesicles (EVs), naturally secreted by almost all known cell types into extracellular space, can transfer their bioactive cargos of nucleic acids and proteins to recipient cells, mediating cell-cell communication. Thus, they participate in many pathogenic processes including immune regulation, cell proliferation and differentiation, cell death, angiogenesis, among others. Cumulative evidence has shown the important regulatory effects of EVs on the initiation and progression of inflammation, autoimmunity, and cancer. In dermatology, recent studies indicate that EVs play key immunomodulatory roles in inflammatory skin disorders, including psoriasis, atopic dermatitis, lichen planus, bullous pemphigoid, systemic lupus erythematosus, and wound healing. Importantly, EVs can be used as biomarkers of pathophysiological states and/or therapeutic agents, both as carriers of drugs or even as a drug by themselves. In this review, we will summarize current research advances of EVs from different cells and their implications in inflammatory skin disorders, and further discuss their future applications, updated techniques, and challenges in clinical translational medicine.
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Carluccio M, Ziberi S, Zuccarini M, Giuliani P, Caciagli F, Di Iorio P, Ciccarelli R. Adult mesenchymal stem cells: is there a role for purine receptors in their osteogenic differentiation? Purinergic Signal 2020; 16:263-287. [PMID: 32500422 DOI: 10.1007/s11302-020-09703-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 05/04/2020] [Indexed: 02/06/2023] Open
Abstract
The role played by mesenchymal stem cells (MSCs) in contributing to adult tissue homeostasis and damage repair thanks to their differentiation capabilities has raised a great interest, mainly in bone regenerative medicine. The growth/function of these undifferentiated cells of mesodermal origin, located in specialized structures (niches) of differentiated organs is influenced by substances present in this microenvironment. Among them, ancestral and ubiquitous molecules such as adenine-based purines, i.e., ATP and adenosine, may be included. Notably, extracellular purine concentrations greatly increase during tissue injury; thus, MSCs are exposed to effects mediated by these agents interacting with their own receptors when they act/migrate in vivo or are transplanted into a damaged tissue. Here, we reported that ATP modulates MSC osteogenic differentiation via different P2Y and P2X receptors, but data are often inconclusive/contradictory so that the ATP receptor importance for MSC physiology/differentiation into osteoblasts is yet undetermined. An exception is represented by P2X7 receptors, whose expression was shown at various differentiation stages of bone cells resulting essential for differentiation/survival of both osteoclasts and osteoblasts. As well, adenosine, usually derived from extracellular ATP metabolism, can promote osteogenesis, likely via A2B receptors, even though findings from human MSCs should be implemented and confirmed in preclinical models. Therefore, although many data have revealed possible effects caused by extracellular purines in bone healing/remodeling, further studies, hopefully performed in in vivo models, are necessary to identify defined roles for these compounds in favoring/increasing the pro-osteogenic properties of MSCs and thereby their usefulness in bone regenerative medicine.
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Affiliation(s)
- Marzia Carluccio
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100, Chieti, Italy.,Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100, Chieti, Italy.,StemTeCh Group, Via L. Polacchi, 66100, Chieti, Italy
| | - Sihana Ziberi
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100, Chieti, Italy.,Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100, Chieti, Italy.,StemTeCh Group, Via L. Polacchi, 66100, Chieti, Italy
| | - Mariachiara Zuccarini
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100, Chieti, Italy.,Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100, Chieti, Italy
| | - Patricia Giuliani
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100, Chieti, Italy.,Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100, Chieti, Italy
| | - Francesco Caciagli
- Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100, Chieti, Italy
| | - Patrizia Di Iorio
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100, Chieti, Italy.,Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100, Chieti, Italy
| | - Renata Ciccarelli
- Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini 29, 66100, Chieti, Italy. .,Center for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Via L. Polacchi, 66100, Chieti, Italy. .,StemTeCh Group, Via L. Polacchi, 66100, Chieti, Italy.
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HB-EGF Improves the Hair Regenerative Potential of Adipose-Derived Stem Cells via ROS Generation and Hck Phosphorylation. Int J Mol Sci 2019; 21:ijms21010122. [PMID: 31878047 PMCID: PMC6981845 DOI: 10.3390/ijms21010122] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 12/18/2019] [Accepted: 12/18/2019] [Indexed: 02/06/2023] Open
Abstract
Although adipose-derived stem cells (ASCs) have hair regenerative potential, their hair inductive capabilities are limited. The mitogenic and hair inductive effects of heparin binding-epidermal growth factor-like growth factor (HB-EGF) on ASCs were investigated in this study and the underlying mechanism of stimulation was examined. Cell growth, migration, and self-renewal assays, as well as quantitative polymerase chain reactions and immunostaining, were carried out. Telogen-to-anagen transition and organ culture using vibrissa follicles were also conducted. HB-EGF significantly increased ASC motility, including cell proliferation, migration, and self-renewal activity. The preconditioning of ASCs with HB-EGF induced telogen-to-anagen transition more rapidly in vivo, and injected PKH26-ASCs survived for longer periods of time. Conditioned medium obtained from HB-EGF-treated ASCs promoted hair growth in vivo, upregulating growth factors. In particular, thrombopoietin (THPO) also induced hair growth in vivo, stimulating dermal papilla cells (DPCs). Reactive oxygen species (ROS) appeared to play a key role in ASC stimulation as the inhibition of ROS generation and NOX4 knockout attenuated ASC stimulation and THPO upregulation by HB-EGF. In addition, the Hck phosphorylation pathway mediated the stimulation of ASCs by HB-EGF. In summary, HB-EGF increased the motility and paracrine effects of ASCs releasing THPO growth factor and THPO promoted hair growth-stimulating DPCs. ROS generation and Hck phosphorylation are key factors in HB-EGF-induced ASC stimulation. Therefore, combination therapy involving HB-EGF and ASCs may provide a novel solution for hair-loss treatment.
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Choi N, Sung JH. Udenafil Induces the Hair Growth Effect of Adipose-Derived Stem Cells. Biomol Ther (Seoul) 2019; 27:404-413. [PMID: 30971059 PMCID: PMC6609107 DOI: 10.4062/biomolther.2018.195] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 01/01/2019] [Accepted: 02/25/2019] [Indexed: 12/25/2022] Open
Abstract
Udenafil, which is a PDE5 inhibitor, is used to treat erectile dysfunction. However, it is unclear whether udenafil induces hair growth via the stimulation of adipose-derived stem cells (ASCs). In this study, we investigated whether udenafil stimulates ASCs and whether increased growth factor secretion from ASCs to facilitate hair growth. We found that subcutaneous injection of udenafil-treated ASCs accelerated telogen-to-anagen transition in vivo. We also observed that udenafil induced proliferation, migration and tube formation of ASCs. It also increased the secretion of growth factors from ASCs, such as interleukin-4 (IL-4) and IL12B, and the phosphorylation of ERK1/2 and NFκB. Furthermore, concomitant upregulation of IL-4 and IL12B mRNA levels was attenuated by ERK inhibitor or NFκB knockdown. Application of IL-4 or IL12B enhanced anagen induction in mice and increased hair follicle length in organ culture. The results indicated that udenafil stimulates ASC motility and increases paracrine growth factor, including cytokine signaling. Udenafil-stimulated secretion of cytokine from ASCs may promote hair growth via the ERK and NFκB pathways. Therefore, udenafil can be used as an ASC-preconditioning agent for hair growth.
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Affiliation(s)
- Nahyun Choi
- College of Pharmacy, Yonsei University, Incheon 21983, Republic of Korea.,STEMORE Co. Ltd., Incheon 21984, Republic of Korea
| | - Jong-Hyuk Sung
- College of Pharmacy, Yonsei University, Incheon 21983, Republic of Korea.,STEMORE Co. Ltd., Incheon 21984, Republic of Korea
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Kruglikov IL, Zhang Z, Scherer PE. The Role of Immature and Mature Adipocytes in Hair Cycling. Trends Endocrinol Metab 2019; 30:93-105. [PMID: 30558832 PMCID: PMC6348020 DOI: 10.1016/j.tem.2018.11.004] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 10/29/2018] [Accepted: 11/20/2018] [Indexed: 02/06/2023]
Abstract
Hair follicles (HFs) strongly interact with adipocytes within the dermal white adipose tissue (dWAT), suggesting a strong physiological dependence on the content of immature and mature adipocytes in this layer. This content is regulated by the proliferation and differentiation of adipocyte precursors, as well as by dedifferentiation of mature existing adipocytes. Spatially, long-range interactions between HFs and dWAT involve the exchange of extracellular vesicles which are differentially released by precursors, preadipocytes, and mature adipocytes. Different exogenous factors, including light irradiation, are likely to modify the release of adipocyte-derived exosomes in dWAT, which can lead to aberrations of the HF cycle. Consequently, dWAT should be considered as a potential target for the modulation of hair growth.
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Affiliation(s)
| | - Zhuzhen Zhang
- Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA
| | - Philipp E Scherer
- Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA.
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Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells. Int J Mol Sci 2018; 19:ijms19030691. [PMID: 29495622 PMCID: PMC5877552 DOI: 10.3390/ijms19030691] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 02/24/2018] [Accepted: 02/26/2018] [Indexed: 01/09/2023] Open
Abstract
Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.
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Tabatabaei Qomi R, Sheykhhasan M. Adipose-derived stromal cell in regenerative medicine: A review. World J Stem Cells 2017; 9:107-117. [PMID: 28928907 PMCID: PMC5583529 DOI: 10.4252/wjsc.v9.i8.107] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 04/30/2017] [Accepted: 05/18/2017] [Indexed: 02/06/2023] Open
Abstract
The application of appropriate cell origin for utilizing in regenerative medicine is the major issue. Various kinds of stem cells have been used for the tissue engineering and regenerative medicine. Such as, several stromal cells have been employed as treat option for regenerative medicine. For example, human bone marrow-derived stromal cells and adipose-derived stromal cells (ADSCs) are used in cell-based therapy. Data relating to the stem cell therapy and processes associated with ADSC has developed remarkably in the past 10 years. As medical options, both the stromal vascular and ADSC suggests good opportunity as marvelous cell-based therapeutics. The some biological features are the main factors that impact the regenerative activity of ADSCs, including the modulation of the cellular immune system properties and secretion of bioactive proteins such as cytokines, chemokines and growth factors, as well as their intrinsic anti-ulcer and anti-inflammatory potential. A variety of diseases have been treated by ADSCs, and it is not surprising that there has been great interest in the possibility that ADSCs might be used as therapeutic strategy to improve a wider range of diseases. This is especially important when it is remembered that routine therapeutic methods are not completely effective in treat of diseases. Here, it was discuss about applications of ADSC to colitis, liver failure, diabetes mellitus, multiple sclerosis, orthopaedic disorders, hair loss, fertility problems, and salivary gland damage.
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Affiliation(s)
- Reza Tabatabaei Qomi
- Department of Stem Cell, the Academic Center for Education, Culture and Research, PO Box QOM-3713189934, Qom, Iran
| | - Mohsen Sheykhhasan
- Department of Stem Cell, the Academic Center for Education, Culture and Research, PO Box QOM-3713189934, Qom, Iran
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