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Guimond, J. V.

Publications and source records attributed to Guimond, J. V..

2 recordsLinked to original sources

The tumor immune response is not compromised by mesenchymal stromal cells in humanized mice

Therapeutic uses of mesenchymal stromal cells (MSCs) have emerged over the past decade. Yet, their effect on tumor growth remains highly debated, particularly in an immune competent environment. Here, we wanted to investigate the impact of human umbilical cord MSCs (hUC-MSCs) on tumor growth in humanized mice generated by the adoptive transfer of peripheral blood mononuclear cells (Hu-AT) or the co-transplantation of hematopoietic stem cells and human thymic tissue (Hu-BLT). Our results showed that the growth and immune rejection of engineered human tumors was not altered by the injection of hUC-MSCs in immune-deficient or humanized mice respectively. This was observed whether tumor cells were injected subcutaneously or intravenously and independently of the injection route of the hUC-MSCs. Moreover, only in Hu-BLT mice did hUC-MSCs have some effects on the tumor immune infiltrate, yet without altering tumor growth. These results demonstrate that hUC-MSCs do not promote tumor growth and neither do they prevent tumor infiltration and rejection by immune cells in humanized mice.

cell biology

Immune Responses to Human Induced Pluripotent Stem Cells and their Derived Myogenic Progenitors Are Mediated by Different Mechanisms in Humanized Mice

It is still unclear if immune responses will compromise the large scale utilization of cell therapies derived from human induced pluripotent stem cells (hiPSCs). To answer this question, we used humanized mouse models and evaluated the engraftment in skeletal muscle of myoblasts derived either directly from a muscle biopsy or differentiated from hiPSCs or fibroblasts. Our results showed that while allogeneic grafts were rejected, engraftment of autologous cells was tolerated, indicating reprogramming and differentiation procedures are not immunogenic. We also demonstrated that hiPSC-derived myogenic progenitors, in opposition to hiPSCs, are not targeted by natural killer (NK) cells both in vitro and in vivo. Yet, adoptive transfer of NK cells can prevent the formation of hiPSC-derived teratoma. Overall, our findings suggest that hiPSC-derived muscular therapies will be tolerated in presence of a competent human immune system and highlight the risk of forming a teratoma if using partially differentiated autologous human cells. HighlightsO_LIhiPSC-derived myofibers are tolerated in autologous humanized mouse models C_LIO_LIInfiltration of autologous T cells is not predictive of successful skeletal muscle engraftment C_LIO_LIAdoptive transfer of NK cells prevents the formation of hiPSCs derived teratomas C_LIO_LINK cells are unable to reject established teratomas C_LI

cell biology