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

Youfeng Li | Zendy; Yuning Zhang | Zendy; Hua Wang | Zendy; Chengfeng Sun | Zendy; Dongmei Liu | Zendy; Hongying Liu | Zendy; Jia He | Zendy; FuRong Chen | Zendy; WeiTing Wang | Zendy; Xi Jiang | Zendy; Chu-Tse Wu | Zendy; Yuefeng Yang | Zendy

Open Access

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

Author(s) -

Youfeng Li,

Yuning Zhang,

Hua Wang,

Chengfeng Sun,

Dongmei Liu,

Hongying Liu,

Jia He,

FuRong Chen,

WeiTing Wang,

Xi Jiang,

Chu-Tse Wu,

Yuefeng Yang

Publication year - 2021

Publication title -

stem cells international

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.205

H-Index - 64

eISSN - 1687-9678

pISSN - 1687-966X

DOI - 10.1155/2021/5585255

Subject(s) - mesenchymal stem cell , angiogenesis , arteriogenesis , hepatocyte growth factor , medicine , therapeutic angiogenesis , vascular endothelial growth factor , neovascularization , cancer research , immunology , bone marrow , pathology , receptor , vegf receptors

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-1 α ). 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-1 α . In conclusion, DP-MSCs might be a promising approach for treating CLI.

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