Wound Healing by Allogeneic Transplantation of Umbilical Cord Mesenchymal Stem Cells in different species

IRIBARNE, AILEN; PALMA, MARIA BELEN; SEOANE ROCHA, CAMILA; ANDRINI LAURA; RICCILLO FERNANDO; BUERO GUILLERMO; TORRES, MARCOS; BRUNO, SANTIAGO; PELINSKI PABLO; MIRIUKA, SANTIAGO G.; CAROSELLA, EDGARDO D.; GARCÍA, MARCELA N.

Paris

Conferencia; 9th International Conference on HLA-G; 2022

CEA, DRF-Francois Jacob Institute SRHI, Saint-Louis Hospital

In normal physiological conditions, restoration of a functional epidermal barrier is highly efficient; nevertheless, some pathologies can interfere with this barrier generating a chronic ulcerative skin defect, one of the most frequently recognized complications of diabetes. Most of these chronic venous ulcers do not heal with conventional treatment, leading to the appearance of infections and complications in the patient. Treatments based on the use of autologous mesenchymal stem cells (MSC) have been successful; however, its implementation entails complications. The umbilical cord offers an unlimited source of adult MSC (ucMSC) from the Wharton’s jelly tissue with the same relevant features for clinical applicability and avoiding difficulties. The present work aims to demonstrate the safety, efficacy, and therapeutic potencial of the use of human, murine, and equine ucMSCs in the healing of chronic dermal wounds in each one of the species. The immune chekpoint (IC) HLA G and VEGF expression in human ucMSCs has been extensively demonstrated, however, our intention is to show that other species such as the equine (not just the mouse) have a similar HLA G protein structure and function. Upon co-culture with both, the human and equine ucMSC, peripheral blood mononuclear cell proliferation was inhibited, demonstrating that ucMSCs are able to generate a tolerogenic environment. In a xenograft transplantation assay, murine, equine, and human ucMSC improved wound healing with no signs of rejection of the transplanted cells in immunocompetent mice. This study confirms that HLA-G, the Q2a functional mouse orthologue, and similar IC protein in equine cells allow allogeneic and xenogeneic cell transplantation. ucMSC could play a very important role in regenerative medicine, not only in humans but also in other species such as horses, which also present significant complications in skin lesions on the legs. These umbilical cord-derived cells could generate a new and effective therapeutic alternative for individuals with dermal chronic injuries resistant to conventional treatments.