title: Human Wharton's jelly stem cells and its conditioned medium enhance healing of excisional and diabetic wounds.
abstract: Wound healing is a major problem in diabetic patients and current treatments have met with limited success. We evaluated the treatment of excisional and diabetic wounds using a stem cell isolated from the human umbilical cord Wharton's jelly (hWJSC) that shares unique properties with embryonic and adult mesenchymal stem cells. hWJSCs are non-controversial, available in abundance, hypo-immunogenic, non-tumorigenic, differentiate into keratinocytes, and secrete important molecules for tissue repair. When human skin fibroblasts (CCD) in conventional scratch-wound assays were exposed to hWJSC-conditioned medium (hWJSC-CM) the fibroblasts at the wound edges migrated and completely covered the spaces by day 2 compared to controls. The number of invaded cells, cell viability, total collagen, elastin, and fibronectin levels were significantly greater in the hWJSC-CM treatment arm compared to controls (P < 0.05). When a single application of green fluorescent protein (GFP)-labeled hWJSCs (GFP-hWJSCs) or hWJSC-CM was administered to full-thickness murine excisional and diabetic wounds, healing rates were significantly greater compared to controls (P < 0.05). Wound biopsies collected at various time points showed the presence of green GFP-labeled hWJSCs, positive human keratinocyte markers (cytokeratin, involucrin, filaggrin) and expression of ICAM-1, TIMP-1, and VEGF-A. On histology, the GFP-hWJSCs and hWJSC-CM treated wounds showed reepithelialization, increased vascularity and cellular density and increased sebaceous gland and hair follicle numbers compared to controls. hWJSCs showed increased expression of several miRNAs associated with wound healing compared to CCDs. Our studies demonstrated that hWJSCs enhance healing of excisional and diabetic wounds via differentiation into keratinocytes and release of important molecules.
authors.affiliation: Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, 119228, Singapore.
authors.forename: Chui-Yee
authors.initials: CY
authors.lastname: Fong
authors.forename: Kimberley
authors.initials: K
authors.lastname: Tam
authors.forename: Suganya
authors.initials: S
authors.lastname: Cheyyatraivendran
authors.forename: Shu-Uin
authors.initials: SU
authors.lastname: Gan
authors.forename: Kalamegam
authors.initials: K
authors.lastname: Gauthaman
authors.forename: Arunmozhiarasi
authors.initials: A
authors.lastname: Armugam
authors.forename: Kandiah
authors.initials: K
authors.lastname: Jeyaseelan
authors.forename: Mahesh
authors.initials: M
authors.lastname: Choolani
authors.forename: Arijit
authors.initials: A
authors.lastname: Biswas
authors.forename: Ariff
authors.initials: A
authors.lastname: Bongso
mesh_terms: D000368:Aged; D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D017077:Culture Media, Conditioned / Q000378:metabolism; D048909:Diabetes Complications / Q000473:pathology / Q000628:therapy*; D003920:Diabetes Mellitus / Q000473:pathology / Q000628:therapy*; D005260:Female; D000091344:Filaggrin Proteins; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D014470:Umbilical Cord / Q000166:cytology; D014945:Wound Healing
chemical_list: D017077:Culture Media, Conditioned; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D035683:MicroRNAs
keywords: EXCISIONAL AND DIABETIC WOUNDS; HUMAN WHARTON'S JELLY STEM CELLS (hWJSCs); SCRATCH-WOUND ASSAY; WOUND HEALING; XENOGRAFT MURINE MODEL; hWJSC CONDITIONED MEDIUM