pretreatment with a γ-secretase inhibitor prevents tumor-like overgrowth in human ipsc-derived transplants for spinal cord injury

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ID: 241829
2016
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Ranked #83 of 101 articles by views in nature reviews gastroenterology & hepatology

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Abstract
Neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) are considered to be a promising cell source for cell-based interventions that target CNS disorders. We previously reported that transplanting certain hiPSC-NS/PCs in the spinal cord results in tumor-like overgrowth of hiPSC-NS/PCs and subsequent deterioration of motor function. Remnant immature cells should be removed or induced into more mature cell types to avoid adverse effects of hiPSC-NS/PC transplantation. Because Notch signaling plays a role in maintaining NS/PCs, we evaluated the effects of γ-secretase inhibitor (GSI) and found that pretreating hiPSC-NS/PCs with GSI promoted neuronal differentiation and maturation in vitro, and GSI pretreatment also reduced the overgrowth of transplanted hiPSC-NS/PCs and inhibited the deterioration of motor function in vivo. These results indicate that pretreatment with hiPSC-NS/PCs decreases the proliferative capacity of transplanted hiPSC-NS/PCs, triggers neuronal commitment, and improves the safety of hiPSC-based approaches in regenerative medicine.
Reference Key
okubo2016stempretreatment Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Toshiki Okubo;Akio Iwanami;Jun Kohyama;Go Itakura;Soya Kawabata;Yuichiro Nishiyama;Keiko Sugai;Masahiro Ozaki;Tsuyoshi Iida;Kohei Matsubayashi;Morio Matsumoto;Masaya Nakamura;Hideyuki Okano
Journal nature reviews gastroenterology & hepatology
Year 2016
DOI
10.1016/j.stemcr.2016.08.015
URL
http://www.sciencedirect.com/science/article/pii/S2213671116301825
Keywords
medicine (general)biology (general)

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