Abstract
Despite significant immunosuppressive activity, allogeneic mesenchymal stromal cells (MSCs) carry an inherent risk of immune rejection when transferred into a recipient. In naïve recipients, this immune response is initially driven by the innate immune system, an immediate reaction to the foreign cells, and later, the adaptive immune system, a delayed response that causes cell death due to recognition of specific alloantigens by host cells and antibodies. This review describes the actions of MSCs to both suppress and activate the different arms of the immune system. We then review the survival and effectiveness of the currently used allogeneic MSC treatments.
Highlights
Bone marrow-derived mesenchymal stromal cells (MSCs) possess immense potential for the treatment of many diseases [1, 2], and there has been rapid acceleration in the clinical use of MSCs [2]
A study using a chemically induced- model of arthritis in the horse showed significant upregulation of type 2 collagen and significantly decreased expression of inflammatory mediators in cartilage at 6 months post-treatment when allogeneic MSC-treated joints were compared to untreated joints, though no significant gross nor histologic improvement was seen (Table 2) [33]
Resounding immunosuppressive effects are seen when MSCs are mixed with activated neutrophils or activated lymphocytes [10, 11, 13, 28,29,30,31, 65]
Summary
Bone marrow-derived mesenchymal stromal cells (MSCs) possess immense potential for the treatment of many diseases [1, 2], and there has been rapid acceleration in the clinical use of MSCs [2]. When suppression of activated lymphocytes is considered, studies have overwhelmingly shown that allogeneic equine MSCs are capable of preventing lymphocyte proliferation in response to an activating agent (phytohaemaglutinin, foreign leukocytes, etc), thereby quelling an immune response [10, 11, 13, 65] This immunosuppression occurs subsequent to the MSC-mediated increase in regulatory T lymphocytes (Tregs) which serve to dampen the adaptive immune response and can prevent rejection of foreign cells by the host [66]. Other work has shown HLA-G causes lymphocyte suppression and increases the number of immunosuppressive Tregs [9] This HLA-G form of the MHC I molecule, which provides an innate ability to prevent the recognition of foreign cells, has likely evolved from the need to prevent fetal attack during gestation [9, 73]. This suggests that CD8+ memory T cells are generated upon original exposure leading to cytotoxic lymphocyte proliferation upon re-injection with MSCs [75]
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