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MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than

Qingguo Zhao1, Carl A Gregory1, Ryang Hwa Lee1

  • 1Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502.

Proceedings of the National Academy of Sciences of the United States of America
|December 31, 2014
PubMed

Insights

Induced pluripotent stem cell-derived mesenchymal stem/stromal cells (iPSC-MSCs) offer a safer alternative to bone marrow MSCs (BM-MSCs) for cancer therapy. These iPSC-MSCs show reduced tumor promotion, addressing limitations of traditional MSCs.

Area of Science:

  • Stem cell biology
  • Cancer research
  • Regenerative medicine

Background:

  • Mesenchymal stem or stromal cells (MSCs) show therapeutic promise for cancer and tissue repair.
  • Tissue-derived MSCs (e.g., bone marrow MSCs) can enhance cancer progression and exhibit donor variability.
  • Limitations of traditional MSCs impede their clinical application, particularly in cancer patients.

Purpose of the Study:

  • To develop and evaluate transgene-free induced pluripotent stem cell-derived MSCs (iPSC-MSCs) as a safer alternative to BM-MSCs.
  • To assess the therapeutic potential and safety profile of iPSC-MSCs in cancer-related applications.

Main Methods:

  • Efficient derivation of MSCs from transgene-free human iPSCs using a modified protocol without flow sorting.
  • Evaluation of iPSC-MSC characteristics: expandability, senescence, teratoma formation, and homing to tumors.
  • Comparative analysis of iPSC-MSCs and BM-MSCs regarding their effects on cancer cell epithelial-mesenchymal transition, invasion, stemness, and growth.

Main Results:

  • iPSC-MSCs were readily expandable, underwent senescence in prolonged culture, and did not form teratomas.
  • iPSC-MSCs exhibited tumor homing similar to BM-MSCs.
  • Significantly reduced promotion of cancer cell epithelial-mesenchymal transition, invasion, stemness, and growth by iPSC-MSCs compared to BM-MSCs.
  • Lower expression of protumorigenic factors (IL-1, TGFβ receptors, hyaluronan, TSG6) in iPSC-MSCs potentially explains reduced tumor promotion.

Conclusions:

  • iPSC-MSCs derived via the modified protocol represent a safer and more effective alternative to BM-MSCs for cancer therapy.
  • The scalable protocol enables large-scale production of iPSC-MSCs for "off-the-shelf" therapies and bioengineering.
  • iPSC-MSCs mitigate key safety concerns associated with BM-MSCs in cancer patients.
Keywords:
canceriPS cellsmesenchymal stem cellsprotumor effectstumor tropism

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