Induced Pluripotent Stem Cells have Similar Immunogenic and More Potent Immunomodulatory Properties Compared with Bone Marrow-Derived Stromal Cells in Vitro

Abstract

Aim: To evaluate the in vitro immunogenic and immunomodulatory properties of induced pluripotent stem cells (iPSCs) compared with bone marrow-derived mesenchymal stromal cells (MSCs). Materials & methods: Mouse embryonic fibroblasts (MEFs) were isolated from C3HeB/FeJ and C57BL/6J mice, and reprogrammed to generate iPSCs. Mixed leukocyte reactions were performed using MHC-matched and -mismatched responder leukocytes and stimulator leukocytes, iPSCs or MSCs. To assess immunogenic potential, iPSCs and MSCs were used as stimulator cells for responder leukocytes. To assess immunomodulatory properties, iPSCs and MSCs were cultured in the presence of stimulator and responder leukocytes. MEFs were used as a control. Results: iPSCs had similar immunogenic properties but more potent immunomodulatory effects than MSCs. Co-culture of MHC-mismatched leukocytes with MHC-matched iPSCs resulted in significantly less responder T-cell proliferation than observed for MHC-mismatched leukocytes alone and at more responder leukocyte concentrations than with MSCs. In addition, MHC-mismatched iPSCs significantly reduced responder T-cell proliferation when co-cultured with MHC-mismatched leukocytes, while MHC-mismatched MSCs did not. Conclusion: These results provide important information when considering the use of iPSCs in place of MSCs in both regenerative and transplantation medicine.

Keywords::

• allogeneic stem cell therapy
• immunogenicity
• immunomodulatory
• induced pluripotent stem cell
• mesenchymal stromal cell
• transplantation medicine

Author contributions

All authors contributed to the study design. LV Schnabel, CM Abratte, JM Cassano and JA Cross performed the experiments. TL Southard carried out histologic assessments on the teratoma assays. All authors contributed to data analysis and interpretation. LV Schnabel and LA Fortier were responsible for drafting the manuscript. All authors revised the manuscript and approved the final version.

Acknowledgements

The authors would like to thank Robert Munroe for his help with animal care and for his contributions to the experimental design. The authors would also like to thank Gina Kemp for her help with animal care and handling.

Financial & competing interests disclosure

This work was supported by Empire State Stem Cell Fund contract no. C024400 (LA Fortier and JC Schimenti) and NIH grant no. 1K08AR060875-01 (LV Schnabel). Finally, the authors would like to acknowledge use of the Cornell University Irradiator Core Facility and support from National Center for Research Resources grant #S10RR023781. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by Empire State Stem Cell Fund contract no. C024400 (LA Fortier and JC Schimenti) and NIH grant no. 1K08AR060875-01 (LV Schnabel). Finally, the authors would like to acknowledge use of the Cornell University Irradiator Core Facility and support from National Center for Research Resources grant #S10RR023781. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.