Department of Chemical and Biological Engineering, University of Colorado , Boulder, Colorado.
Tissue Eng Part B Rev. 2018 Feb;24(1):1-24. doi: 10.1089/ten.TEB.2017.0127. Epub 2017 Jul 3.
Self-assembled microvasculature from cocultures of endothelial cells (ECs) and stromal cells has significantly advanced efforts to vascularize engineered tissues by enhancing perfusion rates in vivo and producing investigative platforms for microvascular morphogenesis in vitro. However, to clinically translate prevascularized constructs, the issue of EC source must be resolved. Endothelial progenitor cells (EPCs) can be noninvasively supplied from the recipient through adult peripheral and umbilical cord blood, as well as derived from induced pluripotent stem cells, alleviating antigenicity issues. EPCs can also differentiate into all tissue endothelium, and have demonstrated potential for therapeutic vascularization. Yet, EPCs are not the standard EC choice to vascularize tissue constructs in vitro. Possible reasons include unresolved issues with EPC identity and characterization, as well as uncertainty in the selection of coculture, scaffold, and culture media combinations that promote EPC microvessel formation. This review addresses these issues through a summary of EPC vascular biology and the effects of tissue engineering design parameters upon EPC microvessel formation. Also included are perspectives to integrate EPCs with emerging technologies to produce functional, organotypic vascularized tissues.
由内皮细胞 (EC) 和基质细胞共培养形成的自组装微血管,通过提高体内灌注率和产生体外微血管形态发生的研究平台,显著推进了工程组织的血管化。然而,要将预血管化的构建物转化为临床应用,就必须解决 EC 来源的问题。内皮祖细胞 (EPC) 可以通过受体的成人外周血和脐带血非侵入性地提供,也可以从诱导多能干细胞中获得,从而减轻抗原性问题。EPC 还可以分化为所有组织的内皮细胞,并显示出治疗性血管化的潜力。然而,EPC 并不是体外血管化组织构建物的标准 EC 选择。可能的原因包括 EPC 身份和特征的未解决问题,以及在促进 EPC 微血管形成的共培养、支架和培养基组合的选择方面存在不确定性。本综述通过总结 EPC 的血管生物学以及组织工程设计参数对 EPC 微血管形成的影响来解决这些问题。还包括将 EPC 与新兴技术相结合以产生功能性、器官样血管化组织的观点。