Reliable generation of glial enriched progenitors from human fibroblast-derived iPSCs.
Reliable generation of glial enriched progenitors from human fibroblast-derived iPSCs.
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DOI：
10.1016/j.scr.2021.102458
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发表时间：
2021-08
影响因子：
1.2
通讯作者：
Carmichael ST
中科院分区：
文献类型：
--
作者：
Llorente IL;Hatanaka EA;Meadow ME;Xie Y;Lowry WE;Carmichael ST
White matter stroke (WMS) occurs as small infarcts in deep penetrating blood vessels in the brain and affects the regions of the brain that carry connections, termed the subcortical white matter. WMS progresses over years and has devastating clinical consequences. Unlike large grey matter strokes, WMS disrupts the axonal architecture of the brain and depletes astrocytes, oligodendrocyte lineage cells, axons and myelinating cells, resulting in abnormalities of gait and executive function. An astrocytic cell-based therapy is positioned as a strong therapeutic candidate after WMS. In this study we report, the reliable generation of a novel stem cell-based therapeutic product, glial enriched progenitors (GEPs) derived from human induced pluripotent stem cells (hiPSCs). By transient treatment of hiPSC derived neural progenitors (hiPSC-NPCs) with the small molecule deferoxamine, a prolyl hydroxylase inhibitor, for three days hiPSC-NPCs become permanently biased towards an astrocytic fate, producing hiPSC-GEPs. In preparation for clinical application, we have developed qualification assays to ensure identity, safety, purity, and viability of the cells prior to manufacture. Using tailored q-RT-PCR-based assays, we have demonstrated the lack of pluripotency in our final therapeutic candidate cells (hiPSC-GEPs) and we have identified the unique genetic profile of hiPSC-GEPs that is clearly distinct from the parent lines, hiPSCs and iPSC-NPCs. After completion of the viability assay, we have stablished the therapeutic window of use for hiPSC-GEPs in future clinical applications (7 h). Lastly, we were able to reliably and consistently produce a safe therapeutic final product negative for contamination by any human or murine viral pathogens, selected bacteria, common laboratory mycoplasmas, growth of any aerobes, anaerobes, yeast, or fungi and 100 times less endotoxin levels than the maximum acceptable value. This study demonstrates the reliable and safe generation of patient derived hiPSC-GEPs that are clinically ready as a cell-based therapeutic approach for WMS.
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DOI：
10.1126/science.1247391
发表时间：
2014-08-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fox IJ;Daley GQ;Goldman SA;Huard J;Kamp TJ;Trucco M
通讯作者：
Trucco M
影响因子：
5.9
作者：
Douvaras, Panagiotis;Wang, Jing;Zimmer, Matthew;Hanchuk, Stephanie;O'Bara, Melanie A.;Sadiq, Saud;Sim, Fraser J.;Goldman, James;Fossati, Valentina
通讯作者：
Fossati, Valentina
影响因子：
7.5
作者：
Hazim RA;Karumbayaram S;Jiang M;Dimashkie A;Lopes VS;Li D;Burgess BL;Vijayaraj P;Alva-Ornelas JA;Zack JA;Kohn DB;Gomperts BN;Pyle AD;Lowry WE;Williams DS
通讯作者：
Williams DS
影响因子：
8.3
作者：
Bliss, Tonya;Guzman, Raphael;Steinberg, Gary K.
通讯作者：
Steinberg, Gary K.
影响因子：
3
作者：
Filous, Angela R.;Miller, Jared H.;Coulson-Thomas, Yvette M.;Horn, Kevin P.;Alilain, Warren J.;Silver, Jerry
通讯作者：
Silver, Jerry