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.

Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

“…On the other hand, other studies have revealed that transplanted MSCs do not necessarily have to be in close proximity to damaged tissue to promote wound repair and functional recovery, thereby suggesting that paracrine factor secretion is the main MSC therapeutic action concerned in repairing skin disorders [129,130]. This theory has been further reinforced by recent studies which have shown that allogeneic MSCs-conditioned medium has enhanced healing when administered locally into wounds [121,122,[131][132][133][134].…”

Acellular Gelatinous Material of Human Umbilical Cord Enhances Wound Healing: A Candidate Remedy for Deficient Wound Healing

“…There is a substantial amount of literature which investigate the beneficial effects of cellular therapy with WJ-MSCs, alone or within a scaffold (Zebardast et al, 2010; Azari et al, 2011; Shohara et al, 2012; Arno et al, 2014; Fong et al, 2014; Ribeiro et al, 2014; Sabapathy et al, 2014). Emerging reports are showing the promising role of decellularized biological matrices for tissue repair (Boccafoschi et al, 2015).…”

“…Wharton's jelly-derived MSCs have the ability to maintain phenotypic attributes, cell growth kinetics, cell cycle pattern, in vitro multilineage differentiation plasticity, apoptotic pattern, normal karyotype-like intrinsic MSC properties in long-term in vitro cultures (Sabapathy et al, 2014). Several studies have investigated cellular therapy with WJ-MSCs, alone or within a scaffold (Azari et al, 2011; Shohara et al, 2012; Fong et al, 2014; Ribeiro et al, 2014; Sabapathy et al, 2014). Studies have elucidated the role of WJ-MSCs for various applications, such as for neurological disorders (Shalitin et al, 2003), kidney injury (Du et al, 2013), lung injury (Moodley et al, 2009), liver injury and cancer therapy (Sabapathy et al, 2014).…”

Conditioned Medium of Wharton's Jelly Derived Stem Cells Can Enhance the Cartilage Specific Genes Expression by Chondrocytes in Monolayer and Mass Culture Systems

“…28 Stem cells derived from umbilical cord Wharton’s jelly show high proliferative capacity, can differentiate into the three germ lineages, are available in large numbers and have prolonged stemness characteristic‏. 29,30 These advantages combined with their non-controversial nature and non-tumorogenicity make them attractive cell source for cell-based therapy‏. 15 The exact mechanism by which WJ-SCs exert their function isn’t yet completely known but they can affect the other cell’s behavior through secretion of specific molecules such as cytokines and growth factors‏.…”