Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies

Deepak Bhere, Rajiv Kumar Khajuria, William T. Hendriks, Antara Bandyopadhyay, Tugba Bagci-Onder, Khalid Shah

Research output: Contribution to journalArticle

Abstract

Stem cells are emerging as promising treatment strategies for several brain disorders and pathologies. In this study, we explored the potential of creating induced pluripotent stem cell-derived neural stem cells (ipNSC) by using either unmodified or gene-modified somatic cells and tested their fate and therapeutic efficacies in vitro and in vivo. We show that cells engineered in somatic state lose transgene-expression during the neural induction process, which is partially restored by histone deacetylase inhibitor treatment whereas cells engineered at the ipNSC state have sustained expression of transgenes. In vivo, bimodal mouse and human ipNSCs engineered to express tumor specific death-receptor ligand and suicide-inducing therapeutic proteins have profound anti-tumor efficacy when encapsulated in synthetic extracellular matrix and transplanted in mouse models of resected-glioblastoma. This study provides insights into using somatic cells for treating CNS disorders and presents a receptor-targeted cancer therapeutic approach for brain tumors. Stem Cells 2018;36:932–942.

Original languageEnglish
Pages (from-to)932-942
Number of pages11
JournalStem Cells
Volume36
Issue number6
DOIs
Publication statusPublished - 01-06-2018
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Bhere, D., Khajuria, R. K., Hendriks, W. T., Bandyopadhyay, A., Bagci-Onder, T., & Shah, K. (2018). Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies. Stem Cells, 36(6), 932-942. https://doi.org/10.1002/stem.2805