Robust and highly-efficient differentiation of functional monocytic cells from human pluripotent stem cells under serum- and feeder cell-free conditions

在无血清和无饲养细胞条件下,人类多能干细胞可稳健高效地分化出功能性单核细胞

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作者:Masakatsu D Yanagimachi, Akira Niwa, Takayuki Tanaka, Fumiko Honda-Ozaki, Seiko Nishimoto, Yuuki Murata, Takahiro Yasumi, Jun Ito, Shota Tomida, Koichi Oshima, Isao Asaka, Hiroaki Goto, Toshio Heike, Tatsutoshi Nakahata, Megumu K Saito

Abstract

Monocytic lineage cells (monocytes, macrophages and dendritic cells) play important roles in immune responses and are involved in various pathological conditions. The development of monocytic cells from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is of particular interest because it provides an unlimited cell source for clinical application and basic research on disease pathology. Although the methods for monocytic cell differentiation from ESCs/iPSCs using embryonic body or feeder co-culture systems have already been established, these methods depend on the use of xenogeneic materials and, therefore, have a relatively poor-reproducibility. Here, we established a robust and highly-efficient method to differentiate functional monocytic cells from ESCs/iPSCs under serum- and feeder cell-free conditions. This method produced 1.3 × 10(6) ± 0.3 × 10(6) floating monocytes from approximately 30 clusters of ESCs/iPSCs 5-6 times per course of differentiation. Such monocytes could be differentiated into functional macrophages and dendritic cells. This method should be useful for regenerative medicine, disease-specific iPSC studies and drug discovery.

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