Effects of Erythropoietin in Murine-Induced Pluripotent Cell-Derived Panneural Progenitor Cells

• Автори: Nils Offen (Автор), Johannes Flemming (Автор), Hares Kamawal (Автор), Ruhel Ahmad (Автор), Wanja Wolber (Автор), Christian Geis (Автор), Holm Zaehres (Автор), Hans R. Schöler (Автор), Hannelore Ehrenreich (Автор), Albrecht M. Müller (Автор), Anna-Leena Sirén (Автор)
• Формат: Книга
• Опубліковано: BMC, 2013-11-01T00:00:00Z.
• Предмети: article
• Онлайн доступ: Connect to this object online.

Резюме

Abstract Induced cell fate changes by reprogramming of somatic cells offers an efficient strategy to generate autologous pluripotent stem (iPS) cells from any adult cell type. The potential of iPS cells to differentiate into various cell types is well established, however the efficiency to produce functional neurons from iPS cells remains modest. Here, we generated panneural progenitor cells (pNPCs) from mouse iPS cells and investigated the effect of the neurotrophic growth factor erythropoietin (EPO) on their survival, proliferation and neurodifferentiation. Under neural differentiation conditions, iPS-derived pNPCs gave rise to microtubule-associated protein-2 positive neuronlike cells (34% to 43%) and platelet-derived growth factor receptor positive oligodendrocytelike cells (21% to 25%) while less than 1% of the cells expressed the astrocytic marker glial fibrillary acidic protein. Neuronlike cells generated action potentials and developed active presynaptic terminals. The pNPCs expressed EPO receptor (EPOR) mRNA and displayed functional EPOR signaling. In proliferating cultures, EPO (0.1-3 U/mL) slightly improved pNPC survival but reduced cell proliferation and neurosphere formation in a concentration-dependent manner. In differentiating cultures EPO facilitated neurodifferentiation as assessed by the increased number of γ-III-tubulin positive neurons. Our results show that EPO inhibits iPS pNPC self-renewal and promotes neurogenesis.

Опис примірника

10.2119/molmed.2013.00136
1076-1551
1528-3658