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创伤性肌肉来源的多能祖细胞通过血管内皮生长因子-A 作用招募内皮细胞。

Traumatized muscle-derived multipotent progenitor cells recruit endothelial cells through vascular endothelial growth factor-A action.

机构信息

Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, School of Medicine.

Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA.

出版信息

J Tissue Eng Regen Med. 2017 Nov;11(11):3038-3047. doi: 10.1002/term.2205. Epub 2017 Jan 12.

Abstract

Traumatized muscle, such as that debrided from blast injury sites, is considered a promising and convenient tissue source for multipotent progenitor cells (MPCs), a population of adult mesenchymal stem cell (MSC)-like cells. The present study aimed to assess the regenerative therapeutic potential of human traumatized muscle-derived MPCs, e.g., for injury repair in the blast-traumatized extremity, by comparing their pro-angiogenic potential in vitro and capillary recruitment activity in vivo to those of MSCs isolated from human bone marrow, a widely-used tissue source. MPCs were tested for their direct and indirect effects on human microvascular endothelial cells (ECs) in vitro. The findings reported here showed that MPC-conditioned culture medium (MPC-CM), like MSC-CM, promoted EC-cord network branching. Silent (si)RNA-mediated silencing of vascular endothelial growth factor-A (VEGF-A) expression in MPCs attenuated this effect. In a chick embryonic chorioallantoic membrane in vivo angiogenesis assay, MPCs encapsulated in photocrosslinked gelatin scaffold recruited blood vessels more efficiently than either MSCs or human foreskin fibroblasts. Together, these findings support the potential application of traumatized muscle-derived MPCs in cell-based regenerative medicine therapies as a result of their influence on EC organization. Copyright © 2017 John Wiley & Sons, Ltd.

摘要

创伤肌肉,如从爆炸伤部位切除的肌肉,被认为是多能祖细胞(MPC)的有前途和方便的组织来源,MPC 是一种类似于成人间充质干细胞(MSC)的细胞群体。本研究旨在评估人创伤肌肉来源的 MPC 的再生治疗潜力,例如,通过比较其在体外的促血管生成潜力和体内毛细血管募集活性,与从广泛使用的组织来源人骨髓中分离的 MSC 进行比较,以评估其在爆炸伤肢体损伤修复中的作用。MPC 被测试其在体外对人微血管内皮细胞(EC)的直接和间接作用。这里报道的研究结果表明,MPC 条件培养基(MPC-CM)与 MSC-CM 一样,促进 EC 索状网络分支。在 MPC 中的沉默(si)RNA 介导的血管内皮生长因子-A(VEGF-A)表达沉默减弱了这种作用。在鸡胚绒毛尿囊膜体内血管生成试验中,包封在光交联明胶支架中的 MPC 比 MSC 或人包皮成纤维细胞更有效地募集血管。总之,这些发现支持了创伤肌肉来源的 MPC 在基于细胞的再生医学治疗中的潜在应用,因为它们对 EC 组织的影响。版权所有©2017 约翰威立父子公司

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