Mesenchymal stromal cells to modulate immune reconstitution early post-hematopoietic cell transplantation.

Elizabeth O Stenger,Jacques Galipeau,Lakshmanan Krishnamurti

doi:10.1186/s12865-015-0135-7

Elizabeth O Stenger, Jacques Galipeau + Show 1 more

Open Access

https://doi.org/10.1186/s12865-015-0135-7

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Abstract

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells known to modulate the immune system and to promote hematopoiesis. These dual effects make MSCs attractive for use as cellular therapy in hematopoietic cell transplantation (HCT). MSCs can be used peri-HCT or pre-engraftment to modulate immune reconstitution, promoting hematopoietic stem cell (HSC) engraftment and/or preventing graft-versus-host disease (GVHD). Pre-clinical studies have demonstrated that MSCs can potentiate HSC engraftment and prevent GVHD in a variety of animal models. Clinical trials have been small and largely non-randomized but have established safety and early evidence of efficacy, supporting the need for larger randomized trials.

Highlights

Mesenchymal Stromal Cells in Hematopoietic Cell Transplantation Mesenchymal stromal cells (MSCs) are multipotent progenitors that promote hematopoiesis and have unique immunoregulatory properties, making them attractive for use as cell-based therapy during and post hematopoietic cell transplantation (HCT)
Administration of MSCs in HCT Based upon their dual role in supporting hematopoiesis and modulating immunity, MSCs have been studied in the peri- and early post-transplant period to promote engraftment and immune reconstitution
MSCs indicates mesenchymal stromal cells, HSC hematopoietic stem cell, PB peripheral blood, Cy cytoxan, Thio thiotepa, Carbo carboplatin, n/a not applicable, BM bone marrow, FBS fetal bovine serum, NR not reported, d days, matchedsibling donor (MSD) matched sibling donor, CSA cyclosporine, MTX methotrexate, aGVHD acute graft-versus-host disease, cGVHD chronic graft-versus-host disease, non-malignant diseases (NMD) non-malignant disease, haplo haploidentical, T cell depletion (TCD) T cell depleted, TBI total body irradiation, DFS disease-free survival, OS overall survival, HR high-risk, UCB umbilical cord blood, eATG equine antithymocyte globulin, MP methylprednisone, HSA human serum albumin, CR1 complete remission 1, HLH hemophagocytic lymphohistiocytosis, SCD sickle cell disease, UD unrelated donor, Flu fludarabine, Mel melphalan neutrophil and platelet engraftment compared to a historical control group, it is the only study to use autologous MSCs and the only following autologous HCT [29]

Summary

Background

Mesenchymal Stromal Cells in Hematopoietic Cell Transplantation Mesenchymal stromal cells (MSCs) are multipotent progenitors that promote hematopoiesis and have unique immunoregulatory properties, making them attractive for use as cell-based therapy during and post hematopoietic cell transplantation (HCT). MSCs have been given in the late post-transplant period primarily as treatment for graft-versus-host disease (GVHD), and there are currently over twenty open studies for this indication registered at https://www.clinicaltrials.gov/. Administration of MSCs in HCT Based upon their dual role in supporting hematopoiesis and modulating immunity, MSCs have been studied in the peri- and early post-transplant period to promote engraftment and immune reconstitution. CD271+ MSCs contained the entire colonyforming unit (CFU)-fibroblast activity (with none in CD271− fraction) and had 1–3 fold higher proliferation compared to standard MSCs (so-called plastic adherent or PA-MSCs) [24] While both MSC subsets increased engraftment, CD271+ MSCs resulted in greater CD45+ donor cell engraftment than PA-MSC [24].

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5-6 Gy 3 Gy

Findings

Conclusions