Mesenchymal stromal cells of human umbilical cord Wharton's jelly accelerate wound healing by paracrine mechanisms |
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| Authors: | Ryutaro Shohara Akihito Yamamoto Sachiko Takikawa Akira Iwase Hideharu Hibi Fumitaka Kikkawa Minoru Ueda |
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| Affiliation: | 1. Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan;2. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan;1. Regenerative Medicine Institute, NUI Galway, Galway, Ireland;2. Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA;3. Discipline of Anatomy, NUI Galway, Galway, Ireland;4. Department of Anatomy, University College Cork, Cork, Ireland;5. School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia;1. Maine Medical Center Research Institute, Scarborough, ME; and;2. Graduate School of Biomedical Sciences, University of Maine, Orono, ME;1. 3B’s Research Group, Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Taipas, Guimarães, Portugal;2. ICVS/3B’s Portuguese Government Associate Laboratory, Braga, Portugal;1. CHU Sainte-Justine Research Center, Center of Cancerology Charles-Bruneau, Montreal, Quebec, Canada;2. Department of Microbiology and Immunology, University of Montreal, Montreal, Quebec, Canada;3. Department of Paediatrics, University of Montreal, Montreal, Quebec, Canada;1. PhD Candidate, Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan;2. Graduate Student, Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan;3. Graduate Student, Department of General Medicine, National Defense Medical College, Saitama, Japan;4. Assistant Professor, Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan;6. Professor, Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan;5. Professor, Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan;1. Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Va;2. The Vascular and Cardiac Center for Adult Stem Cell Therapy, Indiana University School of Medicine, Indianapolis, Ind |
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| Abstract: | ![]()
Background aimsMesenchymal stromal cells (MSC) can be isolated from the perivascular connective tissue of umbilical cords, called Wharton's jelly. These human umbilical cord perivascular cells (HUCPVC) might provide therapeutic benefits when treating skeletal or cutaneous malformations in neonatal patients.MethodsHUCPVC were isolated, and their proliferation rate, marker expression and multilineage differentiation potential determined. HUCPVC or their conditioned medium (HUCPVC-CM) was injected into the excisional wound of a mouse splinted-wound model. The effects of the treatment on wound closure were examined by morphohistochemical and gene expression analyses.ResultsHUCPVC expressed typical MSC markers and could differentiate into osteoblastic and adipogenic lineages. HUCPVC transplanted into the mouse wound accelerated wound closure. Immunohistologic analysis showed that the HUCPVC accelerated wound healing by enhancing collagen deposition and angiogenesis via paracrine mechanisms. Furthermore, treatment with HUCPVC-CM alone significantly enhanced wound closure. HUCPVC-CM increased the number of anti-inflammatory M2 macrophages expressing resistin-like molecule (RELM)-α/CD11b and promoted neovessel maturation. Quantitative polymerase chain reaction (PCR) analysis showed that HUCPVC-CM increased the expression of tissue-repairing cytokines interleukin (IL)-10, transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF)-1 and angiopoietin-1 at the healing wound.ConclusionsOur results show that HUCPVC promotes wound healing via multifaceted paracrine mechanisms. Together with their ability to differentiate into the osteogenic linage, HUCPVC may provide significant therapeutic benefits for treating wounds in neonatal patients. |
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