TY - JOUR
T1 - A robust vitronectin-derived peptide for the scalable long-term expansion and neuronal differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (hNPCs)
AU - Varun, Divya
AU - Srinivasan, Gayathri Rajaram
AU - Tsai, Yi Huan
AU - Kim, Hyun Je
AU - Cutts, Joshua
AU - Petty, Francis
AU - Merkley, Ryan
AU - Stephanopoulos, Nicholas
AU - Dolezalova, Dasa
AU - Marsala, Martin
AU - Brafman, David
N1 - Publisher Copyright:
© 2016 Acta Materialia Inc.
PY - 2017/1/15
Y1 - 2017/1/15
N2 - Despite therapeutic advances, neurodegenerative diseases and disorders remain some of the leading causes of mortality and morbidity in the United States. Therefore, cell-based therapies to replace lost or damaged neurons and supporting cells of the central nervous system (CNS) are of great therapeutic interest. To that end, human pluripotent stem cell (hPSC) derived neural progenitor cells (hNPCs) and their neuronal derivatives could provide the cellular ‘raw material’ needed for regenerative medicine therapies for a variety of CNS disorders. In addition, hNPCs derived from patient-specific hPSCs could be used to elucidate the underlying mechanisms of neurodegenerative diseases and identify potential drug candidates. However, the scientific and clinical application of hNPCs requires the development of robust, defined, and scalable substrates for their long-term expansion and neuronal differentiation. In this study, we rationally designed a vitronectin-derived peptide (VDP) that served as an adhesive growth substrate for the long-term expansion of several hNPC lines. Moreover, VDP-coated surfaces allowed for the directed neuronal differentiation of hNPC at levels similar to cells differentiated on traditional extracellular matrix protein-based substrates. Overall, the ability of VDP to support the long-term expansion and directed neuronal differentiation of hNPCs will significantly advance the future translational application of these cells in treating injuries, disorders, and diseases of the CNS.
AB - Despite therapeutic advances, neurodegenerative diseases and disorders remain some of the leading causes of mortality and morbidity in the United States. Therefore, cell-based therapies to replace lost or damaged neurons and supporting cells of the central nervous system (CNS) are of great therapeutic interest. To that end, human pluripotent stem cell (hPSC) derived neural progenitor cells (hNPCs) and their neuronal derivatives could provide the cellular ‘raw material’ needed for regenerative medicine therapies for a variety of CNS disorders. In addition, hNPCs derived from patient-specific hPSCs could be used to elucidate the underlying mechanisms of neurodegenerative diseases and identify potential drug candidates. However, the scientific and clinical application of hNPCs requires the development of robust, defined, and scalable substrates for their long-term expansion and neuronal differentiation. In this study, we rationally designed a vitronectin-derived peptide (VDP) that served as an adhesive growth substrate for the long-term expansion of several hNPC lines. Moreover, VDP-coated surfaces allowed for the directed neuronal differentiation of hNPC at levels similar to cells differentiated on traditional extracellular matrix protein-based substrates. Overall, the ability of VDP to support the long-term expansion and directed neuronal differentiation of hNPCs will significantly advance the future translational application of these cells in treating injuries, disorders, and diseases of the CNS.
KW - Defined conditions
KW - Human neural progenitor cells
KW - Human pluripotent stem cells
KW - Peptide
UR - http://www.scopus.com/inward/record.url?scp=85006293281&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85006293281&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2016.10.037
DO - 10.1016/j.actbio.2016.10.037
M3 - Article
C2 - 27989923
AN - SCOPUS:85006293281
SN - 1742-7061
VL - 48
SP - 120
EP - 130
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -