Local control of the host immune response performed with mesenchymal stem cells: perspectives for functional intracerebral xenotransplantation

Abstract

Foetal pig neuroblasts are interesting candidates as a cell source for transplantation, but xenotransplantation in the brain requires the development of adapted immunosuppressive treatments. As systemic administration of high doses of cyclosporine A has side effects and does not protect xenotransplants forever, we focused our work on local control of the host immune responses. We studied the advantage of cotransplanting syngenic mesenchymal stem cells (MSC) with porcine neuroblasts (pNb) in immunocompetent rat striata. Two groups of animals were transplanted, either with pNb alone or with both MSC and pNb. At day 63, no porcine neurons were detected in the striata that received only pNb, while four of six rats transplanted with both pNb and MSC exhibited healthy porcine neurons. Interestingly, 50% of the cotransplanted rats displayed healthy grafts with pNF70+ and TH+ neurons at 120 days post-transplantation. qPCR analyses revealed a general dwindling of pro- and anti-inflammatory cytokines in the striata that received the cotransplants. Motor recovery was also observed following the transplantation of pNb and MSC in a rat model of Parkinson's disease. Taken together, the present data indicate that the immunosuppressive properties of MSC are of great interest for the long-term survival of xenogeneic neurons in the brain.

Human mesenchymal stromal cells decrease mortality after intestinal ischemia and reperfusion injury

“…These responses are often short lived though, and tend to diminish over time (33). However, as previously mentioned, the benefits of hBMSC therapy clearly come within the first 12-24 hours of therapy, as many animals exposed to intestinal I/R injury that were not treated with hBMSCs succumbed during this time period.…”

Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats

“…Many studies referring to MSC tracing have demonstrated that intravenously engrafted MSCs are mostly intercepted by microvessels of the lung, heart, liver, kidney, etc., as well as homing to inflammatory and injured areas [11–14]. Importantly, MSCs have been shown to have regenerative, anti-inflammatory, and immunomodulatory capabilities [15–17]. Many experiments and early clinical trials have indicated that MSCs can block the rejection or even induce immune tolerance following transplantation [18, 19].…”

Developments in intracerebral stem cell grafts

“…Human leukocyte antigen (HLA)-matching of donor and recipient may diminish the risk of graft-versus-host disease (GVHD), but this is often not readily achievable [99]. In a different study without systemic immunosuppression, porcine neuroblasts (pNb) cotransplanted with rat MSC intracerebrally can survive up to 120 days [101]. The loss of xenografted neurons is attributed to a host immune response at 4–6 weeks [101].…”

“…In a different study without systemic immunosuppression, porcine neuroblasts (pNb) cotransplanted with rat MSC intracerebrally can survive up to 120 days [101]. The loss of xenografted neurons is attributed to a host immune response at 4–6 weeks [101]. Interestingly, in the presence of MSCs, cellular and molecular events that are usually induced by intracellular transplantation in the rat brain are not observed or are strongly reduced, supporting the notion of MSC as potent immunosuppressors [101].…”

“…The loss of xenografted neurons is attributed to a host immune response at 4–6 weeks [101]. Interestingly, in the presence of MSCs, cellular and molecular events that are usually induced by intracellular transplantation in the rat brain are not observed or are strongly reduced, supporting the notion of MSC as potent immunosuppressors [101]. Human MSCs alter the maturation of dendritic cells as well as their ability to present antigens to T cells, they are also able to inhibit T-cell proliferation, and to affect the differentiation of B cells into plasmocytes [101.…”