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Generation of human vascularized brain organoids

Pham, Missy, T.a; Pollock, Kari, M.a; Rose, Melanie, D.a; Cary, Whitney, A.a; Stewart, Heather, R.a; Zhou, Pinga; Nolta, Jan, A.a; Waldau, Bena,b

doi: 10.1097/WNR.0000000000001014
Degeneration and Repair

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.

aInstitute for Regenerative Cures (IRC)

bDepartment of Neurological Surgery, UC Davis Medical Center, Sacramento, California, USA

Correspondence to Ben Waldau, MD, Department of Neurological Surgery, UC Davis Medical Center, 4680 Y Street, ACC 3740, Sacramento, CA 95817, USA Tel: +1 916 734 6510, fax: +1 916 703 5368; e-mail: bwaldau@ucdavis.edu

Received February 16, 2018

Accepted February 26, 2018

© 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins