Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave., Boston, MA, 02115, USA.
Angiogenesis. 2013 Oct;16(4):735-44. doi: 10.1007/s10456-013-9350-0. Epub 2013 May 1.
Blood-derived endothelial colony-forming cells (ECFCs) have robust vasculogenic potential that can be exploited to bioengineer long-lasting human vascular networks in vivo. However, circulating ECFCs are exceedingly rare in adult peripheral blood. Because the mechanism by which ECFCs are mobilized into circulation is currently unknown, the reliability of peripheral blood as a clinical source of ECFCs remains a concern. Thus, there is a need to find alternative sources of autologous ECFCs. Here we aimed to determine whether ECFCs reside in the vasculature of human white adipose tissue (WAT) and to evaluate if WAT-derived ECFCs have equal clinical potential to blood-derived ECFCs. We isolated the complete endothelial cell (EC) population from intact biopsies of normal human subcutaneous WAT by enzymatic digestion and selection of CD31(+) cells. Subsequently, we extensively compared WAT-derived EC phenotype and functionality to bonafide ECFCs derived from both umbilical cord blood and adult peripheral blood. We demonstrated that human WAT is indeed a dependable source of ECFCs with indistinguishable properties to adult peripheral blood ECFCs, including hierarchical clonogenic ability, large expansion potential, stable endothelial phenotype, and robust in vivo blood vessel-forming capacity. Considering the unreliability and low rate of occurrence of ECFCs in adult blood and that biopsies of WAT can be obtained with minimal intervention in an ambulatory setting, our results indicate WAT as a more practical alternative to obtain large amounts of readily available autologous ECFCs for future vascular cell therapies.
血液来源的内皮祖细胞(ECFCs)具有强大的血管生成潜力,可以利用其在体内构建持久的人类血管网络。然而,成年外周血中循环的 ECFCs 极为罕见。由于 ECFC 动员进入循环的机制尚不清楚,外周血作为 ECFC 的临床来源的可靠性仍然令人担忧。因此,需要寻找替代的自体 ECFC 来源。本研究旨在确定 ECFC 是否存在于人类白色脂肪组织(WAT)的血管中,并评估 WAT 来源的 ECFC 是否具有与血液来源的 ECFC 同等的临床潜力。我们通过酶消化和选择 CD31+细胞从正常人体皮下 WAT 的完整活检中分离出完整的内皮细胞(EC)群体。随后,我们广泛比较了 WAT 来源的 EC 表型和功能与脐带血和成人外周血来源的真正 ECFC。我们证明,人类 WAT 确实是 ECFC 的可靠来源,其特性与成人外周血 ECFC 无法区分,包括分级克隆能力、巨大的扩增潜力、稳定的内皮表型和强大的体内血管生成能力。考虑到成人血液中 ECFC 的不可靠性和低发生率,以及 WAT 活检可以在门诊环境中以最小的干预获得,我们的结果表明 WAT 是获得大量现成自体 ECFC 的更实用的替代方法,用于未来的血管细胞治疗。