Wound Healing Society

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WOUND HEALING ACTIVITY OF HUMAN UMBILICAL CORD BLOOD-DERIVED MESENCHYMAL STEM CELLS ON DIABETIC WOUND
Jae-A Jung, MD, PhD, Kyung-Chul Moon, PhD
Korea University Medical Center, Seoul, South Korea

Recently, there has been increasing interest in the use of cell-based therapies for diabetic wounds. These therapies are designed to modulate the levels of biologic molecules, including growth factors and extracellular matrices that may promote wound healing. Various types of skin substitutes composed of either allogeneic or autologous fibroblasts and/or keratinocytes have been commercialized. Although allogeneic cells, derived from healthy donors, are already available, they may carry the risk of immunologic reactions or cross-infections. Autologous cells are free from these drawbacks. However, they require a long culture time, and, in diabetic patients, autologous cells may not have sufficient capacity to stimulate wound healing. Mesenchymal stem cells (MSCs) may be a good alternative for treating diabetic wounds because they have the advantage of containing both allogeneic and autologous cells. MSCs demonstrate low levels of immunity-assisted rejection and can divide without apoptosis. It was demonstrated that even after 20 or 30 cycles of cell doubling in culture, they still retain initial stem cell properties. Accordingly, MSCs have attracted much interest in the bioengineering field. Bone marrow (BM) stroma is one of the main sources of MSCs. Previous studies performed by our group demonstrated that BM-derived MSCs (BM-MSCs) synthesize higher amounts of collagen, fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) in vitro, as compared with dermal fibroblasts. However, the number of MSCs in the BM decreases with aging and procurement is relatively invasive. In addition, because of issues regarding approval by the Food and Drug Administration (FDA), it is difficult for a clinician to use cultured BM-MSCs for wound healing these days. In the meantime, a novel commercial drug that uses human umbilical cord blood-derived MSCs (hUCB-MSCs) has been developed and achieved recognition by the Korean FDA for helping the regeneration of knee cartilage. Human UCB-MSCs can be obtained in massive quantities without significant ethical issues. Besides, cord blood stem cells are more immature than adult MSCs and can proliferate easily in vitro. Because immune system of newborn is relatively immature than that of adult, cord blood-derived MSCs have been successfully transplanted without causing rejection. Today I will show previous studies performed by our group demonstrated that hUCB-MSCs have superior wound healing activities when compared with both healthy and diabetic fibroblasts not only in vitro but also in vivo studies.


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