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Fu Y, Han YT, Xie JL, Liu RQ, Zhao B, Zhang XL, Zhang J, Zhang J. Mesenchymal stem cell exosomes enhance the development of hair follicle to ameliorate androgenetic alopecia. World J Stem Cells 2025; 17:102088. [PMID: 40160691 PMCID: PMC11947894 DOI: 10.4252/wjsc.v17.i3.102088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 01/21/2025] [Accepted: 02/26/2025] [Indexed: 03/21/2025] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) and their secretome have significant potential in promoting hair follicle development. However, the effects of MSC therapy have been reported to vary due to their heterogeneous characteristics. Different sources of MSCs or culture systems may cause heterogeneity of exosomes. AIM To define the potential of human adipose-derived MSC exosomes (hADSC-Exos) and human umbilical cord-derived MSC exosomes (hUCMSC-Exos) for improving dermal papillary cell proliferation in androgenetic alopecia. METHODS We conducted liquid chromatography-mass spectrometry proteomic analysis of hADSC-Exos and hUCMSC-Exos. Liquid chromatography-mass spectrometry suggested that hADSC-Exos were related to metabolism and immunity. Additionally, the hADSC-Exo proteins regulated the cell cycle and other 9 functional groups. RESULTS We verified that hADSC-Exos inhibited glycogen synthase kinase-3β expression by activating the Wnt/β-catenin signaling pathway via cell division cycle protein 42, and enhanced dermal papillary cell proliferation and migration. Excess dihydrotestosterone caused androgenetic alopecia by shortening the hair follicle growth phase, but hADSC-Exos reversed these effects. CONCLUSION This study indicated that hair development is influenced by hADSC-Exo-mediated cell-to-cell communication via the Wnt/β-catenin pathway.
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Affiliation(s)
- Yu Fu
- Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
| | - Yao-Ting Han
- Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
| | - Jun-Ling Xie
- Research Center for Translational Medicine at East Hospital, School of Medicine, Tongji University, Shanghai 200092, China
| | - Rong-Qi Liu
- Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
| | - Bo Zhao
- Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China
| | - Xing-Liao Zhang
- Research Center for Translational Medicine at East Hospital, School of Medicine, Tongji University, Shanghai 200092, China
| | - Jun Zhang
- Tongji Lifeng Institute of Regenerative Medicine, Tongji University, Shanghai 200092, China
- Research Center for Translational Medicine at East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, School of Medicine, Tongji University, Shanghai 200092, China
| | - Jing Zhang
- Tongji Lifeng Institute of Regenerative Medicine, Tongji University, Shanghai 200092, China
- Research Center for Translational Medicine at East Hospital, School of Life Science, Tongji University, Shanghai 200092, China.
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Davies C, Miron RJ. Autolougous platelet concentrates in esthetic medicine. Periodontol 2000 2025; 97:363-419. [PMID: 39086171 PMCID: PMC11808453 DOI: 10.1111/prd.12582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Revised: 04/15/2024] [Accepted: 05/22/2024] [Indexed: 08/02/2024]
Abstract
This narrative review summarizes current knowledge on the use of autologous platelet concentrates (APCs) in esthetic medicine, with the goal of providing clinicians with reliable information for clinical practice. APCs contain platelets that release various growth factors with potential applications in facial and dermatologic treatments. This review examines several facial esthetic applications of APCs, including acne scarring, skin rejuvenation, melasma, vitiligo, stretchmarks, peri-orbital rejuvenation, peri-oral rejuvenation, hair regeneration and the volumizing effects of APC gels. A systematic review of literature databases (PubMed/MEDLINE) was conducted up to October 2023 to identify randomized controlled trials (RCTs) in the English language on APCs for facial rejuvenation and dermatology. A total of 96 articles were selected including those on platelet rich plasma (PRP), plasma-rich in growth factors (PRGF), and platelet-rich fibrin (PRF). Clinical recommendations gained from the reviews are provided. In summary, the use of APCs in facial esthetics is a promising yet relatively recent treatment approach. Overall, the majority of studies have focused on the use of PRP with positive outcomes. Only few studies have compared PRP versus PRF with all demonstrating superior outcomes using PRF. The existing studies have limitations including small sample sizes and lack of standardized assessment criteria. Future research should utilize well-designed RCTs, incorporating appropriate controls, such as split-face comparisons, and standardized protocols for APC usage, including optimal number of sessions, interval between sessions, and objective improvement scores. Nevertheless, the most recent formulations of platelet concentrates offer clinicians an ability to improve various clinical parameters and esthetic concerns.
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Affiliation(s)
- Catherine Davies
- ZD Hair ClinicJohannesburgSouth Africa
- Advanced PRF EducationVeniceFloridaUSA
| | - Richard J. Miron
- Advanced PRF EducationVeniceFloridaUSA
- Department of PeriodontologyUniversity of BernBernSwitzerland
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Ding YW, Li Y, Zhang ZW, Dao JW, Wei DX. Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment. Bioact Mater 2024; 38:95-108. [PMID: 38699241 PMCID: PMC11061199 DOI: 10.1016/j.bioactmat.2024.04.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 03/27/2024] [Accepted: 04/19/2024] [Indexed: 05/05/2024] Open
Abstract
Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.
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Affiliation(s)
- Yan-Wen Ding
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Department of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China
| | - Yang Li
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Department of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China
| | - Zhi-Wei Zhang
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Department of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China
| | - Jin-Wei Dao
- Dehong Biomedical Engineering Research Center, Dehong Teachers' College, Dehong, Yunnan Province, China
| | - Dai-Xu Wei
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Department of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China
- School of Clinical Medicine, Chengdu University, Chengdu, China
- Shaanxi Key Laboratory for Carbon Neutral Technology, Xi'an, 710069, China
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Fu S, Song X. The clinical and immunological features of alopecia areata following SARS-CoV-2 infection or COVID-19 vaccines. Expert Opin Ther Targets 2024; 28:273-282. [PMID: 38646688 DOI: 10.1080/14728222.2024.2344696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 04/15/2024] [Indexed: 04/23/2024]
Abstract
INTRODUCTION Alopecia areata (AA) is an autoimmune disease induced by viral infection or vaccination. With the increased incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the incidence of AA has also increased. Recently the incidence was found to be 7.8% from a previously reported rate of 2.1%. The physical and psychological damage caused by AA could seriously affect patients' lives, while AA is a challenging dermatological disease owing to its complex pathogenesis. AREAS COVERED This paper presents a comprehensive review of the prevalence, pathogenesis and potential therapeutic targets for AA after infection with SARS-CoV-2 or SARS-CoV-2 vaccine. EXPERT OPINION The treatment of AA remains challenging because of the complexity of its pathogenesis. For patients with AA after SARS-CoV-2 infection or vaccination, the use of sex hormones and alternative regenerative therapies may be actively considered in addition to conventional treatments. For preexisting disease, therapeutic agents should be adjusted to the patient's specific condition.
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Affiliation(s)
- Shiqi Fu
- The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Zhejiang, China
| | - Xiuzu Song
- Department of Dermatology, Hangzhou Third People's Hospital, Affiliated Hangzhou Dermatology Hospital, Hangzhou, China
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Sharma S, Vhadra B, Quinlan DJ, Shatta B, Hassan H. Injectable platelet-rich fibrin for treatment of female pattern hair loss. J COSMET LASER THER 2024; 26:17-25. [PMID: 38989555 DOI: 10.1080/14764172.2024.2374858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 04/05/2024] [Accepted: 06/27/2024] [Indexed: 07/12/2024]
Abstract
This case series evaluated use of injectable platelet rich fibrin (termed i-PRF+) for the treatment of female pattern hair loss (FPHL). Eleven individuals underwent 3-monthly intradermal injections of i-PRF+ using a mesotherapy gun. The mean number of hair follicles containing hairs per unit area improved at 3- and 6-months follow-up (p < .001), and all participants had a negative hair pull test. Hair volume and thickness, and patient-reported outcome scores also improved at follow-up (p < .001). Adverse effects were minor and self-limited. A series of three i-PRF+ injection sessions were effective for the treatment of FPHL, as shown by improved hair analysis parameters and patient self-assessment scores.
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Affiliation(s)
- Shova Sharma
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Bibhuti Vhadra
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Daniel J Quinlan
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Bashar Shatta
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Haidar Hassan
- Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Wang S, Li D, Zou M, Wu J, Wang X, Yang Y, Li X, Yang W. Efficacy of autologous platelet-rich plasma combined with a non-cross-linked hyaluronic acid compound in the treatment of female androgenetic alopecia: A retrospective, case-series study. J Cosmet Dermatol 2023; 22:3268-3275. [PMID: 37337401 DOI: 10.1111/jocd.15861] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 05/15/2023] [Accepted: 05/29/2023] [Indexed: 06/21/2023]
Abstract
BACKGROUND Female androgenetic alopecia (FAGA) is a condition that affects women and involves the gradual loss of terminal hair in specific areas of the scalp. The limited treatment options for FAGA necessitate the development of new strategies. This study aimed to evaluate the potential benefit of using a combination therapy composed of autologous platelet-rich plasma (PRP) and a non-cross-linked hyaluronic acid (HA) compound in the treatment of FAGA. METHODS This was a retrospective, case-series study, which enrolled nine female patients with FAGA between September 2021 and December 2022. The non-cross-linked HA compound (Hearty®, Imeik Technology Development Co., Ltd.) and PRP were implanted into the areas of hair loss over four treatment sessions separated by 4-week intervals. Patients were monitored for overall improvement in their hair loss, hair count, treatment satisfaction, and adverse events at 1, 3, and 6 months follow-up. RESULTS The improvement rates, subjectively evaluated by the study physician, were 88.89% at the 1-month and 100% at the 3-month follow-up, relative to baseline. Moreover, the quantitative evaluation results showed that the FAGA patients' hair density increased by 54.51% at the 1-month and by 77.25% at the 3-month follow-up. CONCLUSION The combination of PRP and non-cross-linked HA compound appeared to be a certain positive effective procedure for FAGA without serious adverse event. We envisage that this work will contribute to the development of new treatment options for women suffering from this condition.
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Affiliation(s)
- Shiwei Wang
- Department of Medical, Imeik Technology Development Co., Ltd., Beijing, China
| | - Dongmei Li
- Department of Medical Cosmetology, Beijing Huaxia Medical Beauty Hospital, Beijing, China
| | - Muyan Zou
- Department of Medical, Imeik Technology Development Co., Ltd., Beijing, China
| | - Jiaxu Wu
- Department of Medical, Imeik Technology Development Co., Ltd., Beijing, China
| | - Xuehan Wang
- Department of Medical Cosmetology, Beijing Huaxia Medical Beauty Hospital, Beijing, China
| | - Yu Yang
- Department of Medical Cosmetology, Beijing Huaxia Medical Beauty Hospital, Beijing, China
| | - Xin Li
- Department of Medical, Imeik Technology Development Co., Ltd., Beijing, China
| | - Wei Yang
- Department of Medical Cosmetology, Beijing Huaxia Medical Beauty Hospital, Beijing, China
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Wang G, Wang Z, Zhang J, Shen Y, Hou X, Su L, Chen W, Chen J, Guo X, Song H. Treatment of androgenetic alopecia by exosomes secreted from hair papilla cells and the intervention effect of LTF. J Cosmet Dermatol 2023; 22:2996-3007. [PMID: 37553912 DOI: 10.1111/jocd.15890] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 05/25/2023] [Accepted: 06/14/2023] [Indexed: 08/10/2023]
Abstract
BACKGROUND Androgenetic alopecia (AGA) is the most common cause of chronic progressive hair loss in men, and AGA has a severe negative impact on the quality of life and physical and mental health of patients. METHODS Four female C57BL/6 mice were isolated from DP cells in culture (≤4 generations) after stimulation of DPC proliferation by herbal concentrations obtained by the CCK-8 method, and exosomes were isolated by differential centrifugation at low temperature. Testosterone propionate and topical hair removal treatments were used together to establish the C57BL/6 mouse AGA model, which was treated with LTF, 5% minoxidil, and LTF-DPC-EXO, respectively. ELISA was used to detect serum hormone levels, in vivo tracing was used to observe dynamic changes in exosomes, H&E staining showed changes in mouse hair follicle tissue, and (q) RT-PCR and WB were used to detect dorsal skin VEGF, AKT1, and CASP3 expression in dorsal skin tissues. RESULTS Hair regeneration was significant in the LTF group, minoxidil group, and LTF-DPC-EXO group mice, and the hair growth was only seen in the local skin in the model group. The hormone T in all treatment groups was lower than that in the model group, and e2 was higher than that in the model group. (q) RT-PCR and western blot showed that VEGF and AKT1 expressions were upregulated and Caspase3 expression was downregulated in the skin sections of mice in the treatment groups. CONCLUSION DPC-EXO obtained through LTF may activate AKT1 and VEGF in the PI3K/AKT signaling pathway to inhibit CASP3, thereby protecting DPC to restore the hair growth.
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Affiliation(s)
- Guiyue Wang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhili Wang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiaqi Zhang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yan Shen
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xin Hou
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Lin Su
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Wen Chen
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiahao Chen
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiang Guo
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Hong Song
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
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Wang L, Qiao S, Xia R, Liu Y, Hu Y, Wu Y, Zhou J, Liang G, Tian T, Cao L. Mesenchymal stromal cell-derived magnetic nanovesicles for enhanced skin retention and hair follicle growth. Cytotherapy 2023; 25:1176-1185. [PMID: 37516947 DOI: 10.1016/j.jcyt.2023.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 06/29/2023] [Accepted: 07/05/2023] [Indexed: 07/31/2023]
Abstract
BACKGROUND AIMS Extracellular vesicles and exosome-mimetic nanovesicles (NVs) derived from mesenchymal stromal cells (MSCs) have emerged as promising to promote hair growth. However, short local skin retention after subcutaneous administration hinders their clinical applications. METHODS In this study, we prepared magnetic nanovesicles (MNVs) from iron oxide nanoparticle-incorporated MSCs. MNVs contained more therapeutic growth factors than NVs derived from naive MSCs, and their localization and internalization were manipulated by external magnetic field. RESULTS Following the subcutaneous injection of MNVs into a mouse model of depilation-induced hair regeneration, the magnetic attraction increased their skin retention. Then, the cellular proliferation and β-catenin signaling in hair follicles (HF) were markedly enhanced by MNV injection and magnetic field application. Furthermore, an acceleration of HF growth was revealed by histological analysis. CONCLUSIONS The proposed strategy can enhance the therapeutic potential of MSC-derived NVs for hair regeneration and other dermatological diseases.
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Affiliation(s)
- Lei Wang
- Department of Dermatology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China
| | - Shuya Qiao
- Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Rushan Xia
- Department of Dermatology, Jiangnan University Medical Center, Wuxi, Jiangsu, China
| | - Yiwen Liu
- Department of Dermatology, Jiangnan University Medical Center, Wuxi, Jiangsu, China
| | - Yifei Hu
- Department of Dermatology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China
| | - Yajuan Wu
- Department of Dermatology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China
| | - Junhao Zhou
- Department of Dermatology, Jiangnan University Medical Center, Wuxi, Jiangsu, China
| | - Gaofeng Liang
- School of Basic Medical Sciences, Henan University of Science & Technology, Luoyang, Henan, China
| | - Tian Tian
- Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Lei Cao
- Department of Dermatology, Jiangnan University Medical Center, Wuxi, Jiangsu, China.
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Wang Z, Feng C, Chang G, Liu H, Li S. The use of platelet-rich plasma in wound healing and vitiligo: A systematic review and meta-analysis. Skin Res Technol 2023; 29:e13444. [PMID: 37753680 PMCID: PMC10444946 DOI: 10.1111/srt.13444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 08/13/2023] [Indexed: 09/28/2023]
Abstract
OBJECTIVE To critically assess the effect and safety of platelet-rich plasma (PRP) in chronic wounds and vitiligo. METHODS A systematic literature searching was performed. Results were expressed as weight mean difference (WMD) or risk ratio (RR) with 95% confidence intervals (CIs). Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. RESULTS A total of 27 studies were included in this meta-analysis. In patients with chronic diabetic ulcers, PRP significantly increased proportion of complete wound healing, percentage of wound area healed, and shortened the complete wound healing. In venous ulcers, PRP improved the epithelialized area and percentage of wound area healed. In vitiligo, PRP had better results in degree of improvement and mean repigmentation than controls. Regarding the safety profile, PRP did not increase the risk of infection in patients with chronic diabetic ulcers. Meta-regression revealed that source of PRP and preparation method of PRP significantly affected the proportion of complete wound healing, whereas age, gender, country, duration of wound, and wound size had no impact on this outcome. CONCLUSION PRP is effective and safe, and can be used as a potential therapeutic adjunct or alternative treatment in chronic wounds of multiple etiologies and vitiligo.
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Affiliation(s)
- Zhi Wang
- Department of Plastic & Cosmetic SurgeryPeking Union Medical College HospitalBeijingChina
| | - Cheng Feng
- Department of Plastic & Cosmetic SurgeryPeking Union Medical College HospitalBeijingChina
| | - Guojing Chang
- Department of Plastic & Cosmetic SurgeryPeking Union Medical College HospitalBeijingChina
| | - Hao Liu
- Department of Plastic & Cosmetic SurgeryPeking Union Medical College HospitalBeijingChina
| | - Shuo Li
- Department of Plastic & Cosmetic SurgeryPeking Union Medical College HospitalBeijingChina
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Huerta CT, Ortiz YY, Liu ZJ, Velazquez OC. Methods and Limitations of Augmenting Mesenchymal Stem Cells for Therapeutic Applications. Adv Wound Care (New Rochelle) 2023; 12:467-481. [PMID: 36301919 PMCID: PMC10254976 DOI: 10.1089/wound.2022.0107] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 09/27/2022] [Indexed: 11/13/2022] Open
Abstract
Significance: Given their capacity for self-renewal, multilineage differentiation, and immunomodulatory potential, mesenchymal stem cells (MSCs) represent a promising modality of clinical therapy for both regenerative medicine and immune diseases. In this study, we review the key approaches and popular methods utilized to boost potency and modify functions of MSCs for clinical purposes as well as their associated limitations. Recent Advances: Several major domains of cell modification strategies are currently employed by investigators to overcome these deficits and augment the therapeutic potential of MSCs. Priming MSCs with soluble factors or pharmacologic agents as well as manipulating oxygen availability in culture have been demonstrated to be effective biochemical methods to augment MSC potential. Distinct genetic and epigenetic methods have emerged in recent years to modify the genetic expression of target proteins and factors thereby modulating MSCs capacity for differentiation, migration, and proliferation. Physical methods utilizing three-dimensional culture methods and alternative cell delivery systems and scaffolds can be used to recapitulate the native MSC niche and augment their engraftment and viability for in vivo models. Critical Issues: Unmodified MSCs have demonstrated only modest benefits in many preclinical and clinical studies due to issues with cell engraftment, viability, heterogeneity, and immunocompatibility between donor and recipient. Furthermore, unmodified MSCs can have low inherent therapeutic potential for which intensive research over the past few decades has been dedicated to improving cell functionality and potency.
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Affiliation(s)
- Carlos Theodore Huerta
- DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Yulexi Y. Ortiz
- DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Zhao-Jun Liu
- DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
- Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Omaida C. Velazquez
- DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
- Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
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Piccini I, Sousa M, Altendorf S, Jimenez F, Rossi A, Funk W, Bíró T, Paus R, Seibel J, Jakobs M, Yesilkaya T, Edelkamp J, Bertolini M. Intermediate Hair Follicles from Patients with Female Pattern Hair Loss Are Associated with Nutrient Insufficiency and a Quiescent Metabolic Phenotype. Nutrients 2022; 14:3357. [PMID: 36014862 PMCID: PMC9416027 DOI: 10.3390/nu14163357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/10/2022] [Accepted: 08/11/2022] [Indexed: 11/28/2022] Open
Abstract
Female pattern hair loss (FPHL) is a non-scarring alopecia resulting from the progressive conversion of the terminal (t) scalp hair follicles (HFs) into intermediate/miniaturized (i/m) HFs. Although data supporting nutrient deficiency in FPHL HFs are lacking, therapeutic strategies are often associated with nutritional supplementation. Here, we show by metabolic analysis that selected nutrients important for hair growth such as essential amino acids and vitamins are indeed decreased in affected iHFs compared to tHFs in FPHL scalp skin, confirming nutrient insufficiency. iHFs also displayed a more quiescent metabolic phenotype, as indicated by altered metabolite abundance in freshly collected HFs and release/consumption during organ culture of products/substrates of TCA cycle, aerobic glycolysis, and glutaminolysis. Yet, as assessed by exogenous nutrient supplementation ex vivo, nutrient uptake mechanisms are not impaired in affected FPHL iHFs. Moreover, blood vessel density is not diminished in iHFs versus tHFs, despite differences in tHFs from different FPHL scalp locations or versus healthy scalp or changes in the expression of angiogenesis-associated growth factors. Thus, our data reveal that affected iHFs in FPHL display a relative nutrient insufficiency and dormant metabolism, but are still capable of absorbing nutrients, supporting the potential of nutritional supplementation as an adjunct therapy for FPHL.
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Affiliation(s)
- Ilaria Piccini
- Monasterium Laboratory Skin & Hair Research Solutions GmbH, 48149 Münster, Germany
| | - Marta Sousa
- Monasterium Laboratory Skin & Hair Research Solutions GmbH, 48149 Münster, Germany
| | - Sabrina Altendorf
- Monasterium Laboratory Skin & Hair Research Solutions GmbH, 48149 Münster, Germany
| | - Francisco Jimenez
- Mediteknia Hair Transplant Clinic and Hair Lab, Universidad Fernando Pessoa Canarias, Gran Canaria, Canary Islands, 35450 Guía, Spain
| | - Alfredo Rossi
- Department of Clinical Internal Anesthesiological and Cardiovascular Sciences, “Sapienza” University of Rome, 00161 Rome, Italy
| | | | - Tamás Bíró
- Monasterium Laboratory Skin & Hair Research Solutions GmbH, 48149 Münster, Germany
| | - Ralf Paus
- Monasterium Laboratory Skin & Hair Research Solutions GmbH, 48149 Münster, Germany
- Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | | | | | | | - Janin Edelkamp
- Monasterium Laboratory Skin & Hair Research Solutions GmbH, 48149 Münster, Germany
| | - Marta Bertolini
- Monasterium Laboratory Skin & Hair Research Solutions GmbH, 48149 Münster, Germany
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Gentile P. Hair Loss and Telogen Effluvium Related to COVID-19: The Potential Implication of Adipose-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma as Regenerative Strategies. Int J Mol Sci 2022; 23:ijms23169116. [PMID: 36012383 PMCID: PMC9409133 DOI: 10.3390/ijms23169116] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/09/2022] [Accepted: 08/12/2022] [Indexed: 11/16/2022] Open
Abstract
The diffusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inducing coronavirus disease 2019 (COVID-19) has increased the incidence of several dermatological disorders, including hair loss (HL). This article aims to review the literature regarding the incidence of HL and telogen effluvium (TE) in COVID-19 patients and critically appraise the available evidence regarding the role of regenerative strategies like Platelet-Rich Plasma (PRP) and Human Follicle Stem Cells (HFSCs). A literature review regarding the correlation of HL and TE in COVID-19 patients analyzing the biomolecular pathway involved and the role of regenerative strategies was performed using PubMed, MEDLINE, Embase, PreMEDLINE, Scopus, and the Cochrane databases. Observational studies revealed an escalated incidence of pattern HL and TE in COVID-19 patients. Psychological stress, systemic inflammation, and oxidative stress are potential culprits. Proinflammatory cytokines and stress hormones negatively affect the normal metabolism of proteoglycans. Reduced anagenic expression of proteoglycans is a potential mediating mechanism that connects HL to COVID-19. Currently, only one study has been published on PRP against HL in COVID-19 patients. Further controlled trials are required to confirm PRP and HFSCs efficacy in COVID-19 patients.
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Affiliation(s)
- Pietro Gentile
- Plastic and Reconstructive Surgery, Department of Surgical Science, "Tor Vergata" University, 00133 Rome, Italy
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Ebrahimi Z, Alimohamadi Y, Janani M, Hejazi P, Kamali M, Goodarzi A. Platelet-rich plasma in the treatment of scars, to suggest or not to suggest? A systematic review and meta-analysis. J Tissue Eng Regen Med 2022; 16:875-899. [PMID: 35795892 DOI: 10.1002/term.3338] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 05/21/2022] [Accepted: 06/12/2022] [Indexed: 11/07/2022]
Abstract
Despite the rising trend for applying platelet-rich plasma (PRP) in the management of various types of scars, there is no convincing evidence supporting its use. This motivated us to review the randomized clinical trials that examine the effectiveness and safety of PRP, alone or in combination with other methods, for the management of atrophic or hypertrophic/keloidal scars. The Web of Science, Scopus, Google Scholar, and Cochrane Library databases were systematically searched until September 1st , 2020. Thirteen clinical trials were enrolled in the meta-analysis, and 10 more were reviewed for their results. The random effect meta-analysis method was used to assess the effect size of each outcome for each treatment type, and I2 was used to calculate the statistical heterogeneity between the studies. Patients treated with PRP experienced an overall response rate of 23%, comparable to the results seen with laser or micro-needling (22% and 23%, respectively) When used alone, moderate improvement was the most frequently observed degree of response with PRP (36%) whereas, when added to laser or micro-needling, most patients experienced marked (33%, 43%, respectively) or excellent (32% and 23%, respectively) results. Concerning the hypertrophic/keloid scars, the only study meeting the required criteria reported a better improvement and fewer adverse effects when PRP was added to the intralesional corticosteroids. Platelet-rich plasma appears to be a safe and effective treatment for various types of atrophic scars. In addition, when added to ablative lasers or micro-needling, it seems to considerably add to the efficacy of treatment and reduce the side effects.
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Affiliation(s)
- Zahra Ebrahimi
- Department of General Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Yousef Alimohamadi
- Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Majid Janani
- Department of Epidemiology & Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Pardis Hejazi
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mahboobeh Kamali
- Air Pollution Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Azadeh Goodarzi
- Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.,Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Chueh KS, Huang KH, Lu JH, Juan TJ, Chuang SM, Lin RJ, Lee YC, Long CY, Shen MC, Sun TW, Juan YS. Therapeutic Effect of Platelet-Rich Plasma Improves Bladder Overactivity in the Pathogenesis of Ketamine-Induced Ulcerative Cystitis in a Rat Model. Int J Mol Sci 2022; 23:ijms23105771. [PMID: 35628581 PMCID: PMC9147926 DOI: 10.3390/ijms23105771] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 05/19/2022] [Accepted: 05/19/2022] [Indexed: 12/15/2022] Open
Abstract
The present study attempted to elucidate whether intravesical instillation of platelet-rich plasma (PRP) could decrease bladder inflammation and ameliorate bladder hyperactivity in ketamine ulcerative cystitis (KIC) rat model. Female Sprague Dawley (S-D) rats were randomly divided into control group, ketamine-treated group, ketamine with PRP treated group, and ketamine with platelet-poor plasma (PPP) treated group. Cystometry and micturition frequency/volume studies were performed to investigate bladder function. The morphological change of bladder was investigated by Mason’s trichrome staining. Western blotting analysis were carried out to examine the protein expressions of inflammation, urothelial differentiation, proliferation, urothelial barrier function, angiogenesis and neurogenesis related proteins. The results revealed that treatment with ketamine significantly deteriorated bladder capacity, decreased voiding function and enhanced bladder overactivity. These pathological damage and interstitial fibrosis may via NF-κB/COX-2 signaling pathways and muscarinic receptor overexpression. PRP treatment decreased inflammatory fibrotic biosynthesis, attenuated oxidative stress, promoted urothelial cell regeneration, and enhanced angiogenesis and neurogenesis, thereafter recovered bladder dysfunction and ameliorate the bladder hyperactivity in KIC rat model. These findings suggested that the PRP therapy may offer new treatment options for those clinical KIC patients.
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Affiliation(s)
- Kuang-Shun Chueh
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (K.-S.C.); (C.-Y.L.)
- Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (S.-M.C.); (M.-C.S.); (T.-W.S.)
| | - Kuan-Hua Huang
- Divisions of Urological Oncology, Department of Surgery, Chi Mei Medical Center, Tainan 71004, Taiwan;
| | - Jian-He Lu
- Emerging Compounds Research Center, Department of Environmental Science and Engineering, College of Engineering, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan;
| | - Tai-Jui Juan
- Department of Medicine, National Defense Medical College, Taipei 11490, Taiwan;
| | - Shu-Mien Chuang
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (S.-M.C.); (M.-C.S.); (T.-W.S.)
| | - Rong-Jyh Lin
- Department of Parasitology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
| | - Yi-Chen Lee
- Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Cheng-Yu Long
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (K.-S.C.); (C.-Y.L.)
- Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Department of Obstetrics and Gynecology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 80708, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Mei-Chen Shen
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (S.-M.C.); (M.-C.S.); (T.-W.S.)
| | - Ting-Wei Sun
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (S.-M.C.); (M.-C.S.); (T.-W.S.)
| | - Yung-Shun Juan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (K.-S.C.); (C.-Y.L.)
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; (S.-M.C.); (M.-C.S.); (T.-W.S.)
- Correspondence: ; Tel.: +886-7-3121101
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