hPSC‐derived Midbrain Dopaminergic Neurons Generated in a Scalable 3‐D Biomaterial

Abstract

Human pluripotent stem cell (hPSC)-derived midbrain dopaminergic (mDA) neurons may facilitate the development of therapies for Parkinson's disease via disease modeling, drug screening, and cell replacement therapy. However, large numbers of cells are typically needed for these applications, and 2-D culture-based approaches typically used for mDA differentiation are difficult to scale up and require a long time for mDA maturation. Here we present a protocol to rapidly generate functional mDA neurons in a fully defined, scalable, thermoresponsive 3-D biomaterial. Resource-efficient and accelerated differentiation of large numbers of mDA neurons may thus facilitate studying and treating PD. © 2018 by John Wiley & Sons, Inc.

Advanced Materials to Enhance Central Nervous System Tissue Modeling and Cell Therapy

“…Stem cell-derived therapies are promising candidates to treat CNS disorders, and the rationale and feasibility of these therapies have been widely explored during recent years. [10,11,13,14] CRTs offer the potential to restore function in the CNS when neurodegenerative conditions have progressed to the stage that significant endogenous cell populations have been lost. [64] In addition, implanted cells could also secrete protective factors to slow disease progression.…”

“…[ 7–9 ] Therefore, the use of stem cells for cell‐replacement therapies offers the unique opportunity to repair the damaged tissue and thereby potentially restore motor and/or cognitive functions. In particular, cortical neurons, [ 10 ] cortical interneurons, [ 11 ] medium spiny neurons, [ 12 ] oligodendrocyte precursors, [ 13 ] and dopaminergic neurons [ 14 ] have been generated by differentiating human stem cells in culture and offer potential to treat neurological conditions.…”

Stem cell‐based therapy for Parkinson’s disease with a focus on human endometrium‐derived mesenchymal stem cells

“…Besides immature neural cells can proliferate unpredictably, resulting in graft overgrowth in an experiment with the PD model. Hence, great research in producing donor cells from iPSCs efforts concentrate on the development of new approaches to regulate the direction of the cell phenotype and the extent of maturation (Adil & Schaffer, 2018;Doi et al, 2012). On the other hand, the poor graft survival rate was accentuated by using mature transplanted neural cells.…”