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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Stem Cells
Induced Pluripotent Stem Cells
Neural Stem Cells
Transgenes
Neoplasms
Death Domain Receptors
Histone Deacetylase Inhibitors
Brain Diseases
Therapeutics
Glioblastoma
Brain Neoplasms
Suicide
Extracellular Matrix
Pathology
Ligands
Genes
Proteins

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
Bhere, Deepak ; Khajuria, Rajiv Kumar ; Hendriks, William T. ; Bandyopadhyay, Antara ; Bagci-Onder, Tugba ; Shah, Khalid. / Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies. In: Stem Cells. 2018 ; Vol. 36, No. 6. pp. 932-942.
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Bhere, D, Khajuria, RK, Hendriks, WT, Bandyopadhyay, A, Bagci-Onder, T & Shah, K 2018, 'Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies', Stem Cells, vol. 36, no. 6, pp. 932-942. https://doi.org/10.1002/stem.2805

Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies. / Bhere, Deepak; Khajuria, Rajiv Kumar; Hendriks, William T.; Bandyopadhyay, Antara; Bagci-Onder, Tugba; Shah, Khalid.

In: Stem Cells, Vol. 36, No. 6, 01.06.2018, p. 932-942.

Research output: Contribution to journalArticle

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Bhere D, Khajuria RK, Hendriks WT, Bandyopadhyay A, Bagci-Onder T, Shah K. Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies. Stem Cells. 2018 Jun 1;36(6):932-942. https://doi.org/10.1002/stem.2805