Vascularization and engraftment of a human skin substitute using circulating progenitor cell-derived endothelial cells
Vascularization and engraftment of a human skin substitute using circulating progenitor cell-derived endothelial cells
复制标题
DOI：
10.1096/fj.05-5682fje
复制
发表时间：
2006-08-01
期刊：
影响因子：
4.8
通讯作者：
Schechner, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Shepherd, Benjamin R.;Enis, David R.;Schechner, Jeffrey S.
我们接种组织工程人类皮肤替代品与内皮细胞（EC）在体外分化的祖细胞从脐带血（CB-EC）或成人外周血（AB-EC），比较结果与以前的工作，使用培养的人脐静脉EC（HUVEC）与或没有Bcl-2转导。通过在表皮表面的角质形成细胞覆盖后将Bcl-2转导或未转导的HUVEC、CB-EC或AB-EC接种在脱细胞的人真皮的深表面上来制备血管化皮肤替代物。将这些皮肤替代物移植到C. B-17 SCID/beige小鼠接受全身雷帕霉素或载体对照，并在21天后进行分析。CB-EC和Bcl-2-HUVEC比AB-EC或对照HUVEC形成更多的人EC衬里的血管; CB-EC、Bcl-2-HUVEC和AB-EC而不是对照HUVEC促进小鼠EC衬里的血管向内生长。Bcl-2转导增加了接种HUVEC的移植物中人类和小鼠EC衬里血管的数量，但不增加CB-EC或AB-EC。CB-EC和AB-EC诱导的微血管都被平滑肌细胞特异性α-肌动蛋白阳性壁细胞所覆盖，表明成熟。雷帕霉素抑制小鼠EC内衬血管的向内生长，但不抑制人EC内衬血管的形成。我们的结论是，EC分化的循环祖细胞可用于血管化人类皮肤替代品，即使在设置受损的主机血管生成/血管生成。
We seeded tissue engineered human skin substitutes with endothelial cells (EC) differentiated in vitro from progenitors from umbilical cord blood (CB-EC) or adult peripheral blood (AB-EC), comparing the results to previous work using cultured human umbilical vein EC (HUVEC) with or without Bcl-2 transduction. Vascularized skin substitutes were prepared by seeding Bcl-2-transduced or nontransduced HUVEC, CB-EC, or AB- EC on the deep surface of decellularized human dermis following keratinocyte coverage of the epidermal surface. These skin substitutes were transplanted onto C. B-17 SCID/beige mice receiving systemic rapamycin or vehicle control and were analyzed 21 d later. CB-EC and Bcl-2-HUVEC formed more human EC-lined vessels than AB- EC or control HUVEC; CB-EC, Bcl-2-HUVEC, and AB- EC but not control HUVEC promoted ingrowth of mouse EC-lined vessels. Bcl-2 transduction increased the number of human and mouse EC-lined vessels in grafts seeded with HUVEC but not with CB-EC or AB- EC. Both CB-EC and AB-EC-induced microvessels became invested by smooth muscle cell-specific alpha-actin-positive mural cells, indicative of maturation. Rapamycin inhibited ingrowth of mouse EC-lined vessels but did not inhibit formation of human EC-lined vessels. We conclude that EC differentiated from circulating progenitors can be utilized to vascularize human skin substitutes even in the setting of compromised host angiogenesis/vasculogenesis.