Mitomycin‐C treatment during differentiation of induced pluripotent stem cell‐derived dopamine neurons reduces proliferation without compromising survival or function in vivo
Abstract 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 |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Stem cells translational medicine - 10(2021), 2, Seite 278-290 |
| Beteiligte Personen: |
Hiller, Benjamin M. [VerfasserIn] |
|---|
| Anmerkungen: |
© 2021 AlphaMed Press |
|---|
| Umfang: |
13 |
|---|
| doi: |
10.1002/sctm.20-0014 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
WLY013184075 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | WLY013184075 | ||
| 003 | DE-627 | ||
| 005 | 20230308014105.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230221s2021 xx |||||o 00| ||und c | ||
| 024 | 7 | |a 10.1002/sctm.20-0014 |2 doi | |
| 028 | 5 | 2 | |a SCT3_SCT312803.xml |
| 035 | |a (DE-627)WLY013184075 | ||
| 035 | |a (WILEY)SCT312803 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 082 | 0 | 4 | |a 610 |q ASE |
| 100 | 1 | |a Hiller, Benjamin M. |e verfasserin |4 aut | |
| 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 |
| 264 | 1 | |c 2021 | |
| 300 | |a 13 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © 2021 AlphaMed Press | ||
| 520 | |a Abstract 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. | ||
| 700 | 1 | |a Marmion, David J. |4 aut | |
| 700 | 1 | |a Gross, Rachel M. |4 aut | |
| 700 | 1 | |a Thompson, Cayla A. |4 aut | |
| 700 | 1 | |a Chavez, Carrie A. |4 aut | |
| 700 | 1 | |a Brundin, Patrik |4 aut | |
| 700 | 1 | |a Wakeman, Dustin R. |4 aut | |
| 700 | 1 | |a McMahon, Christopher W. |4 aut | |
| 700 | 1 | |a Kordower, Jeffrey H. |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Stem cells translational medicine |d Oxford : Oxford University Press, 2012 |g 10(2021), 2, Seite 278-290 |w (DE-627)WLY013180533 |w (DE-600)2642270-0 |x 21576580 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2021 |g number:2 |g pages:278-290 |g extent:13 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_WLY | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2021 |e 2 |h 278-290 |g 13 | ||