Efficacy of topical and systemic transplantation of mesenchymal stem cells in a rat model of diabetic ischemic wounds.
Efficacy of topical and systemic transplantation of mesenchymal stem cells in a rat model of diabetic ischemic wounds.
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间充质干细胞局部和全身移植在糖尿病缺血性伤口大鼠模型中的疗效
DOI：
10.1186/s13287-021-02288-8
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发表时间：
2021-03-31
影响因子：
7.5
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Yan J;Liang J;Cao Y;El Akkawi MM;Liao X;Chen X;Li C;Li K;Xie G;Liu H
BackgroundMesenchymal stem cells (MSCs) exert positive effects in chronic wounds. However, critical parameters, such as the most effective administration routes, remain unclear. Accordingly, the purpose of this study was to compare the effects of topical and systemic transplantation MSCs on diabetic ischemic wound healing and explored the underlying mechanisms.MethodA diabetic ischemic wound model was created on the dorsal foot of type 2 diabetes mellitus (T2DM) rat. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered via two routes: topical injection and intravenous (IV) infusion. Wound healing outcomes and blood glucose level were assessed dynamically. Meanwhile, blood flow recovery was evaluated in ischemic gastrocnemius muscles. The homing and transdifferentiation of mKate2-labeled BM-MSCs were assessed by fluorescence imaging and immunohistochemistry (IHC) analysis.ResultBoth topical and systemic treatments had a positive effect on the diabetic ischemic wound showing a significant reduction in wound area at day 14. Histological results showed an increase in the length of epithelial edges, collagen content, microvessel density in the wound bed, and a higher expression of vascular endothelial growth factor (VEGF). Meanwhile, systemic administration can ameliorate hyperglycemia and improve the blood perfusion of the ischemic hindlimb. BM-MSCs administered systemically were found distributed in wounded tissue and transdifferentiated into endothelial cells. Furthermore, BM-MSCs stimulated angiogenesis at wound sites by downregulating phosphatase and tensin homolog (PTEN) and activation of AKT signaling pathway.ConclusionsThe results demonstrated that both transplantation delivery method (topical and systemic) of BM-MSCs accelerated wound healing remarkably under pathological conditions. Nevertheless, systemic administration has the potential to ameliorate hyperglycemia and repair the damaged tissue.
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影响因子：
13.6
作者：
Ankrum J;Karp JM
通讯作者：
Karp JM
影响因子：
1.6
作者：
Byun JS;Kwak BK;Kim JK;Jung J;Ha BC;Park S
通讯作者：
Park S
影响因子：
2.9
作者：
Gentile, Pietro;Kothari, Ashutosh;Calabrese, Claudio
通讯作者：
Calabrese, Claudio
影响因子：
4
作者：
Evans, Michael;Baddour, Harry Michael, Jr.;Chen, Zhuo G.
通讯作者：
Chen, Zhuo G.
影响因子：
1.7
作者：
Gonzalez Sarasua, J.;Perez Lopez, S.;Otero Hernandez, J.
通讯作者：
Otero Hernandez, J.