Pham Missy T, Pollock Kari M, Rose Melanie D, Cary Whitney A, Stewart Heather R, Zhou Ping, Nolta Jan A, Waldau Ben
Institute for Regenerative Cures (IRC).
Department of Neurological Surgery, UC Davis Medical Center, Sacramento, California, USA.
Neuroreport. 2018 May 2;29(7):588-593. doi: 10.1097/WNR.0000000000001014.
The aim of this study was to vascularize brain organoids with a patient's own endothelial cells (ECs). Induced pluripotent stem cells (iPSCs) of one UC Davis patient were grown into whole-brain organoids. Simultaneously, iPSCs from the same patient were differentiated into ECs. On day 34, the organoid was re-embedded in Matrigel with 250 000 ECs. Vascularized organoids were grown in vitro for 3-5 weeks or transplanted into immunodeficient mice on day 54, and animals were perfused on day 68. Coating of brain organoids on day 34 with ECs led to robust vascularization of the organoid after 3-5 weeks in vitro and 2 weeks in vivo. Human CD31-positive blood vessels were found inside and in-between rosettes within the center of the organoid after transplantation. Vascularization of brain organoids with a patient's own iPSC-derived ECs is technically feasible.
本研究的目的是用患者自身的内皮细胞（ECs）使脑类器官血管化。将一名加州大学戴维斯分校患者的诱导多能干细胞（iPSCs）培育成全脑类器官。同时，将来自同一名患者的iPSCs分化为ECs。在第34天，将类器官重新包埋于含有250000个ECs的基质胶中。血管化类器官在体外培养3 - 5周，或在第54天移植到免疫缺陷小鼠体内，并在第68天对动物进行灌注。在第34天用ECs包被脑类器官，在体外培养3 - 5周和体内培养2周后，类器官实现了强大的血管化。移植后，在类器官中心的玫瑰花结内部和之间发现了人CD31阳性血管。用患者自身的iPSC衍生的ECs使脑类器官血管化在技术上是可行的。
