کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2039676 1073075 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A Cell Engineering Strategy to Enhance the Safety of Stem Cell Therapies
ترجمه فارسی عنوان
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موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• Cancer and normal tissues derived from iPSCs differentially depend on MYC
• MYC sustains tumor-specific metabolic and chromatin changes in iPSC-derived tumors
• Engineering iPSCs with dominant-negative MYC is a therapeutic fail-safe strategy

SummaryThe long-term risk of malignancy associated with stem cell therapies is a significant concern in the clinical application of this exciting technology. We report a cancer-selective strategy to enhance the safety of stem cell therapies. Briefly, using a cell engineering approach, we show that aggressive cancers derived from human or murine induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are strikingly sensitive to temporary MYC blockade. On the other hand, differentiated tissues derived from human or mouse iPSCs can readily tolerate temporary MYC inactivation. In cancer cells, endogenous MYC is required to maintain the metabolic and epigenetic functions of the embryonic and cancer-specific pyruvate kinase M2 isoform (PKM2). In summary, our results implicate PKM2 in cancer’s increased MYC dependence and indicate dominant MYC inhibition as a cancer-selective fail-safe for stem cell therapies.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 8, Issue 6, 25 September 2014, Pages 1677–1685
نویسندگان
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