Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

Abstract

Mesenchymal stem cells (MSCs), an ideal cell source for regenerative therapy with no ethical issues, play an important role in diabetic foot ulcer (DFU). Growing evidence has demonstrated that MSCs transplantation can accelerate wound closure, ameliorate clinical parameters, and avoid amputation. In this review, we clarify the mechanism of preclinical studies, as well as safety and efficacy of clinical trials in the treatment of DFU. Bone marrow-derived mesenchymal stem cells (BM-MSCs), compared with MSCs derived from other tissues, may be a suitable cell type that can provide easy, effective, and cost-efficient transplantation to treat DFU and protect patients from amputation.

Figure 1

Mechanism of BM-MSCs for treatment of DFU. BM-MSCs can migrate and adhere via CCR7, ICAM1-, VCAM1-, and Akt- dependent mechanism and enhance angiogenesis through increasing VEGF, NGF, BDNF, VEGF-A, eNOS, and HIF. Cell proliferation of HUVECs and keratinocytes plays significant role in angiogenesis and reepithelialization, respectively. Keratinocyte function is improved by regulating IGF-1, EGF, MMP-2, MMP-9, TIMP-1, TIMP-2, and Erk signaling pathway. CCR7: C-C chemokine receptor type 7, ICAM1: intercellular adhesion molecule 1, VCAM1: vascular adhesion molecule 1, VEGF: vascular endothelial growth factor, NGF: nerve growth factor, BDNF: brain-derived neurotrophic factor, VEGF-A: vascular endothelial growth factor A, eNOS: endothelial nitric oxide synthase, HIF: hypoxia inducible factor, IGF-1: insulin-like growth factor 1, EGF: epidermal growth factor, MMP-2: matrix metalloproteinase-2, MMP-9: matrix metalloproteinase-9, TIMP-1: tissue inhibitor of metalloproteinase-1, and TIMP-2: tissue inhibitor of metalloproteinase-2.