Stromal vascular fraction promotes migration of fibroblasts and angiogenesis through regulation of extracellular matrix in the skin wound healing process

Autor: Huanran Tan, Yiqing Mao, Hui Li, Ying Xing, Xi Wang, David M. Irwin, Wuga Sha, Hongsen Bi, Chen Zhang, Fangfei Nie
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Angiogenesis
Stromal vascular fraction
medicine.medical_treatment
Medicine (miscellaneous)
Wound healing
Biochemistry
Genetics and Molecular Biology (miscellaneous)
Extracellular matrix
lcsh:Biochemistry
Mice
03 medical and health sciences
0302 clinical medicine
Cell Movement
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
lcsh:QD415-436
Fibroblast
Human adipose-derived stem cells
Cells
Cultured
Skin
030304 developmental biology
Skin repair
0303 health sciences
lcsh:R5-920
Neovascularization
Pathologic
integumentary system
business.industry
Research
3T3 Cells
Cell Biology
Fibroblasts
Coculture Techniques
Extracellular Matrix
3. Good health
Cell biology
Mice
Inbred C57BL
medicine.anatomical_structure
Cytokine
Adipose Tissue
030220 oncology & carcinogenesis
Molecular Medicine
Stromal Cells
Stem cell
business
lcsh:Medicine (General)
Zdroj: Stem Cell Research & Therapy, Vol 10, Iss 1, Pp 1-21 (2019)
Stem Cell Research & Therapy
ISSN: 1757-6512
DOI: 10.1186/s13287-019-1415-6
Popis: Background A refractory wound is a typical complication of diabetes and is a common outcome after surgery. Current approaches have difficulty in improving wound healing. Recently, non-expanded stromal vascular fraction (SVF), which is derived from mature fat, has opened up new directions for the treatment of refractory wound healing. The aim of the current study is to systematically investigate the impact of SVF on wound healing, including the rate and characteristics of wound healing, ability of fibroblasts to migrate, and blood transport reconstruction, with a special emphasis on their precise molecular mechanisms. Methods SVF was isolated by digestion, followed by filtration and centrifugation, and then validated by immunocytochemistry, a MTS proliferation assay and multilineage potential analysis. A wound model was generated by creating 6-mm-diameter wounds, which include a full skin defect, on the backs of streptozocin-induced hyperglycemic mice. SVF or human adipose-derived stem cell (hADSC) suspensions were subcutaneously injected, and the wounds were characterized over a 9-day period by photography and measurements. A scratch test was used to determine whether changes in the migratory ability of fibroblasts occurred after co-culture with hADSCs. Angiogenesis was observed with human umbilical vein endothelial cells. mRNA from fibroblasts, endotheliocyte, and skin tissue were sequenced by high-throughput RNAseq, and differentially expressed genes, and pathways, potentially regulated by SVF or hADSCs were bioinformatically analyzed. Results Our data show that hADSCs have multiple characteristics of MSC. SVF and hADSCs significantly improved wound healing in hyperglycemic mice. hADSCs improve the migratory ability of fibroblasts and capillary structure formation in HUVECs. SVF promotes wound healing by focusing on angiogenesis and matrix remodeling. Conclusions Both SVF and hADSCs improve the function of fibroblast and endothelial cells, regulate gene expression, and promote skin healing. Various mechanisms likely are involved, including migration of fibroblasts, tubulogenesis of endothelial cells through regulation of cell adhesion, and cytokine pathways.
Databáze: OpenAIRE
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