Dental Pulp Mesenchymal Stem Cells Attenuate Limb Ischemia via Promoting Capillary Proliferation and Collateral Development in a Preclinical Model

• Published in: Stem cells international Vol. 2021; pp. 1 - 10
• Main Authors: Li, Youfeng, Zhang, Yuning, Wang, Hua, Sun, Chengfeng, Liu, Dongmei, Liu, Hongying, He, Jia, Chen, Furong, Wang, Weiting, Jiang, Xi, Wu, Chu-tse, Yang, Yuefeng
• Format: Journal Article
• Language: English
• Published: New York Hindawi 01.09.2021; Hindawi Limited; Wiley
• Subjects: Advertising executives; Angiogenesis; Antibodies; Biomedical materials; Bone marrow; Cell proliferation; Chemokines; Comparative analysis; Dental pulp; Deprivation; Differentiation (biology); Femoral artery; Flow velocity; Growth factors; Health aspects; Hepatocyte growth factor; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-inducible factor 1a; Inflammation; Ischemia; Laboratory animals; Medical imaging; Mesenchymal stem cells; Muscles; Regeneration; Stem cells; Therapeutic applications; Umbilical cord; Vascular diseases; Vascular endothelial growth factor; Vascularization; China; Beijing China; Japan
• ISSN: 1687-966X; 1687-9678; 1687-9678
• DOI: 10.1155/2021/5585255

Critical limb ischemia (CLI), an end-stage manifestation of peripheral artery disease (PAD), still lacks effective therapeutic strategies. Recently, dental pulp-derived mesenchymal stem cells (DP-MSCs) have been attracting more and more attentions in therapeutic applications due to their high proliferation ability, powerful osteogenic differentiation potential, and effective anti-inflammatory effects. In this study, we compared the therapeutic effects of MSCs derived from different sources in a femoral artery-ligated preclinical ischemic model. We found that treatments with MSCs, including bone marrow- (BM-), adipose- (AD-), dental pulp- (DP-), and umbilical cord- (UC-) derived MSCs, improved limb functions, reduced inflammatory responses, increased angiogenesis, and promoted regeneration of muscle fiber. Among them, DP-MSCs and BM-MSCs produced much more impressive effects in restoring limb functions and promoting angiogenesis. The flow velocity restored to nearly 20% of the normal level at 3 weeks after treatments with DP-MSCs and BM-MSCs, and obvious capillary proliferation and collateral development could be observed. Although neovascularization was induced in the ischemic limb after ligation, MSCs, especially DP-MSCs, significantly enhanced the angiogenesis. In vitro experiments showed that serum deprivation improved the expression of angiogenic factors, growth factors, and chemokines in DP-MSCs and UC-MSCs, but not in BM-MSCs and AD-MSCs. However, DP-MSCs produced stronger therapeutic responses than UC-MSCs, which might be due to the higher expression of hepatocyte growth factor (HGF) and hypoxia-inducible factor-1 α (HIF-1α). We speculated that DP-MSCs might stimulate angiogenesis and promote tissue repair via expressing and secreting angiogenic factors, growth factors, and chemokines, especially HGF and HIF-1α. In conclusion, DP-MSCs might be a promising approach for treating CLI.