Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo
© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Stem cells translational medicine - 10(2021), 2 vom: 16. Feb., Seite 278-290 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hiller, Benjamin M [VerfasserIn] |
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| Links: |
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| Themen: |
50SG953SK6 |
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| Anmerkungen: |
Date Completed 21.03.2022 Date Revised 21.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/sctm.20-0014 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315679646 |
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| 245 | 1 | 0 | |a Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo |
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| 500 | |a Date Revised 21.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Parkinson's disease | |
| 650 | 4 | |a cell transplantation | |
| 650 | 4 | |a immune-deficient models | |
| 650 | 4 | |a induced pluripotent stem cells | |
| 650 | 7 | |a Mitomycin |2 NLM | |
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| 700 | 1 | |a Marmion, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Gross, Rachel M |e verfasserin |4 aut | |
| 700 | 1 | |a Thompson, Cayla A |e verfasserin |4 aut | |
| 700 | 1 | |a Chavez, Carrie A |e verfasserin |4 aut | |
| 700 | 1 | |a Brundin, Patrik |e verfasserin |4 aut | |
| 700 | 1 | |a Wakeman, Dustin R |e verfasserin |4 aut | |
| 700 | 1 | |a McMahon, Christopher W |e verfasserin |4 aut | |
| 700 | 1 | |a Kordower, Jeffrey H |e verfasserin |4 aut | |
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