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

Abstract

Impaired wound healing is a severe clinical challenge and research into finding effective wound healing strategies is underway as there is no ideal treatment. Gelatinous material from the umbilical cord called Wharton's jelly is a valuable source of mesenchymal stem cells which have been shown to aid wound healing. While the cellular component of Wharton's jelly has been the subject of extensive research during the last few years, little is known about the de-cellularized jelly material of the umbilical cord. This is important as they are native niche of stem cells. We have isolated Wharton's jelly from umbilical cords and then fractionated acellular gelatinous Wharton's jelly (AGWJ). Here, we show for the first time that AGWJ enhances wound healing in vitro as well as in vivo for wounds in a murine model. In vivo staining of the wounds revealed a smaller wound length in the AGWJ treated wounds in comparison to control treatment by enhancing cell migration and differentiation. AGWJ significantly enhanced fibroblast cell migration in vitro. Aside from cell migration, AGWJ changed the cell morphology of fibroblasts to a more elongated phenotype, characteristic of myofibroblasts, confirmed by upregulation of alpha smooth muscle actin using immunoblotting. AGWJ treatment of wounds led to accelerated differentiation of cells into myofibroblasts, shortening the proliferation phase of wound healing. This data provides support for a novel wound healing remedy using AGWJ. AGWJ being native biological, cost effective and abundantly available globally, makes it a highly promising treatment option for wound dressing and skin regeneration.

Promotion of dermal regeneration using pullulan/gelatin porous skin substitute

“…It is known that myofibroblasts contribute to wound closure and scar formation (Amini‐Nik, ; Amini‐Nik et al, ; Arno et al, ; Bakhtyar et al, ; Desmoulière, Chaponnier, & Gabbiani, ; Mak et al, ; Moulin, Auger, Garrel, & Germain, ). Therefore, sustained myofibroblast presence in the proliferation phase of wound healing, although important in the early phase, can lead to scar formation.…”

“…Informed signed consent was obtained from the patients (REB PIN 142‐2015 and UHN REB# 13‐6437‐CE). Normal human skin dermis was used to obtain normal human fibroblasts through the primary cell culture technique (Arno et al, ; Bakhtyar, Jeschke, Mainville, Herer, & Amini‐Nik, ). The study has been approved and reviewed by the REB/IRB of Sunnybrook Research Institute.…”

Use of Human Umbilical Cord and Its Byproducts in Tissue Regeneration

“…Human umbilical cord contains factors that stimulate cell proliferation, migration, tissue differentiation, and growth (Lago et al, 2005;Secunda et al, 2015;Bruschi et al, 2018). Previous work has shown that HUC components can be isolated and used as decellularized scaffolds or extracts which have great regenerative potential (Bakhtyar et al, 2017). Decellularized WJ (DWJ) from HUC was tested as a scaffold where cells migrate and proliferate in vitro.…”

“…Studies have shown that these two migrations cause some MSCs to become trapped in the WJ and remain there for the duration of the gestational period (Wang et al, 2008). The jelly trapped MSCs generates sufficient microenvironment components, such as cytokines and a specific stroma, which ensure the maintenance of the cell population and the preservation of their function (Troyer and Weiss, 2008;Taghizadeh et al, 2011;Bakhtyar et al, 2017). The presence of MSCs in the HUC is the key feature of its regenerative properties (Kalaszczynska and Ferdyn, 2015;Ren et al, 2016).…”

Biomaterials for Skin Substitutes

“…The normal wound healing response and intrinsic tissue regeneration of the skin are not sufficient in cases like acute and large area wounds and burns, or in elderly and diabetic patients . While autologous grafts are considered to be the gold‐standard for skin regeneration, limitations in the donor site availability and complications associated with reharvesting donor sites necessitate the investigation of skin substitutes . Currently, different skin substitutes are being used in clinic.…”