| Autor: |
Doi D; Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan., Samata B; Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan., Katsukawa M; Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan., Kikuchi T; Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan., Morizane A; Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan., Ono Y; Group for Neuronal Differentiation and Development, KAN Research Institute, Inc., 650-0047 Kobe, Japan., Sekiguchi K; Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, 565-0871 Osaka, Japan., Nakagawa M; Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan., Parmar M; Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 221 84 Lund, Sweden., Takahashi J; Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan ; Department of Biological Repair, Institute for Frontier Medical Sciences, Kyoto University, 606-8507 Kyoto, Japan ; Department of Neurosurgery, Kyoto University School of Medicine, 606-8507 Kyoto, Japan. |
| Abstrakt: |
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. |
