[PDF][PDF] Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation

D Doi, B Samata, M Katsukawa, T Kikuchi, A Morizane… - Stem cell reports, 2014 - cell.com
D Doi, B Samata, M Katsukawa, T Kikuchi, A Morizane, Y Ono, K Sekiguchi, M Nakagawa…
Stem cell reports, 2014cell.com
Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain
dopaminergic (DA) neurons for cell replacement therapy for Parkinson's disease. However,
iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. Here, we
show that human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting
using a floor plate marker, CORIN. We induced DA neurons using scalable culture
conditions on human laminin fragment, and the sorted CORIN+ cells expressed the midbrain …
Summary
Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson's disease. However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. Here, we show that human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, CORIN. We induced DA neurons using scalable culture conditions on human laminin fragment, and the sorted CORIN+ cells expressed the midbrain DA progenitor markers, FOXA2 and LMX1A. When transplanted into 6-OHDA-lesioned rats, the CORIN+ cells survived and differentiated into midbrain DA neurons in vivo, resulting in significant improvement of the motor behavior, without tumor formation. In particular, the CORIN+ cells in a NURR1+ cell-dominant stage exhibited the best survival and function as DA neurons. Our method is a favorable strategy in terms of scalability, safety, and efficiency and may be advantageous for clinical application.
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