Open AccessMitomycin‐C treatment during differentiation of induced pluripotent stem cell‐derived dopamine neurons reduces proliferation without compromising survival or function in vivo
Author(s) -
Hiller Benjamin M.,
Marmion David J.,
Gross Rachel M.,
Thompson Cayla A.,
Chavez Carrie A.,
Brundin Patrik,
Wakeman Dustin R.,
McMahon Christopher W.,
Kordower Jeffrey H.
Publication year - 2021
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.1002/sctm.20-0014
Subject(s) - induced pluripotent stem cell , stem cell , mitomycin c , dopamine , transplantation , biology , cellular differentiation , in vivo , cancer research , fgf8 , neuron , microbiology and biotechnology , neuroscience , medicine , embryonic stem cell , genetics , fibroblast growth factor , receptor , gene
Nongenetic methodologies to reduce undesirable proliferation would be valuable when generating dopamine neurons from stem cells for transplantation in Parkinson's disease (PD). To this end, we modified an established method for controlled differentiation of human induced pluripotent stem cells (iPSCs) into midbrain dopamine neurons using two distinct methods: omission of FGF8 or the in‐process use of the DNA cross‐linker mitomycin‐C (MMC). We transplanted the cells to athymic rats with unilateral 6‐hydroxydopamine lesions and monitored long‐term survival and function of the grafts. Transplants of cells manufactured using MMC had low proliferation while still permitting robust survival and function comparable to that seen with transplanted dopamine neurons derived using genetic drug selection. Conversely, cells manufactured without FGF8 survived transplantation but exhibited poor in vivo function. Our results suggest that MMC can be used to reduce the number of proliferative cells in stem cell‐derived postmitotic neuron preparations for use in PD cell therapy.