Amit Srivastava, Abstract Co-Author: Nothing to Disclose

Camille Bulte, Abstract Co-Author: Nothing to Disclose

Irina Shats, Abstract Co-Author: Nothing to Disclose

Piotr Walczak, Abstract Co-Author: Nothing to Disclose

Jeff W.M. Bulte PhD, Presenter: Research Grant, Koninklijke Philips NV Founder and co-owner, SenCEST, LLC

Loss of functional cells from immunorejection during the immediate post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that mesenchymal stem cells (MSCs) exhibit many positive effects when engrafted, including immunomodulation. We investigated whether co-transplantation of MSCs could improve the survival of transplanted therapeutic cells.

Glial-restricted progenitors (GRPs) were isolated from luciferase-transgenic FVB mouse brain (at E13.5 stage). MSCs were isolated from BALB/c mouse bone marrow. Twenty immunocompetent BALB/c and eight immunodeficient Rag2−/− mice (used as control) were intracerebrally transplanted, either with GRPs alone (1x105 cells), or GRPs co-transplanted with MSCs (1x105 cells). No immunosuppression was given. Bioluminescence imaging (BLI) and computed tomography (CT) were performed for 21 days post-transplantation using a PerkinElmer IVIS Spectrum/CT. Immunohistochemical assays were performed to detect inflammation and survival of transplanted cells.

Three-dimensional images generated by co-registering BLI and CT images confirmed the placement of the cells at the site of targeted injection in the brain (Fig. 1A). Normalization of BLI signal intensity with day 1 revealed that on day 21, signal intensity had decreased 96% in animals transplanted with GRPs alone versus 68% in animals co-transplanted with MSCs (p<0.05) (Fig. 1B). On histology, co-transplantation of MSCs effectively suppressed the host immune response against the graft. In the immunodeficient animals, all transplanted GRPs survived regardless whether MSCs were co-transplanted.

In immunocompetent mice without immunosuppression, co-transplantation of MSCs creates a microenvironment that is more conducive to the survival of allogeneic GRPs.

MSCs are already used clinically in a variety of degenerative diseases (i.e., myocardial infarct, multiple sclerosis, and stroke). We show that co-transplantation of MSCs can also improve the survival of other therapeutic cells, which opens up new avenues in stem cell therapies for neuroinflammatory disease.

Srivastava, A, Bulte, C, Shats, I, Walczak, P, Bulte, J, Immunomodulation by Co-Transplanted Mesenchymal Stem Cells Improves Survival of Glial-Restriced Progenitors.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14010772.html