Efficient differentiation of human embryonic and induced pluripotent stem cells into functional astrocytes

Luni Emdad, Sunita L. D'Souza, Harini P. Kothari, Zulekha A. Qadeer, Isabelle M. Germano

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Human high-grade gliomas (hHGG) remain a therapeutic challenge in neuro-oncology despite current multimodality treatments. We recently demonstrated that murine embryonic stem cell (mESC)-derived astrocytes conditionally expressing proapoptotic genes can successfully be used to induce apoptosis and tumor shrinkage of hHGG tumor in vitro and in an in vivo mouse model. The first step in the translation of these results to the clinical settings, however, requires availability of human embryonic stem cells (hESC)-and/or induced pluripotent cell (hiPSC)-derived astrocytes engineered to express proapoptotic genes. The potential for directed differentiation of hESCs and hiPSCs to functional postmitotic astrocytes is not fully characterized. In this study, we show that once specified to neuro-epithelial lineage, hiPSC could be differentiated to astrocytes with a similar efficiency as hESC. However, our analyses of 2hESC and 2 hiPSC cell lines showed some variability in differentiation potential into astrocytic lineages. Both the hESC-and hiPSC-derived astrocytes appeared to follow the functional properties of mESC-derived astrocytes, namely, migration and tropism for hHGG. This work provides evidence that hESC-and hiPSC-derived cells are able to generate functionally active astrocytes. These results demonstrate the feasibility of using iPSC-derived astrocytes, a new potential source for therapeutic use for brain tumors and other neurological diseases.

Original languageEnglish
Pages (from-to)404-410
Number of pages7
JournalStem Cells and Development
Volume21
Issue number3
DOIs
StatePublished - 10 Feb 2012

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