Mesenchymal Stem Cells: A Novel Therapeutic Approach to Enhance Protective Immunomodulation and Erythropoietic Recovery in Malaria

Abstract

Mesenchymal stem cells (MSCs) are self-renewing, multi-potent heterogeneous stem cells that display strong tissue protective and restorative properties by differentiating into cells of the mesodermal lineages. In addition to multi-lineage differentiation capacity, MSCs play important roles in regulating immune responses, inflammation, and tissue regeneration. MSCs play a role in the outcome of the pathogenesis of several infectious diseases. A unique subset of MSCs accumulates in secondary lymphoid organs during malaria disease progression. These MSCs counteract the capacity of malaria parasites to subvert activating co-stimulatory molecules and to regulate expression of negative co-stimulatory molecules on T lymphocytes. Consequently, MSCs have the capacity to restore the functions of CD34+ haematopoietic cells and CD4+ and CD8+ T cells during malaria infection. These observations suggest that cell-based therapeutics for intervention in malaria may be useful in achieving sterile clearance and preventing disease reactivation. In addition, MSCs provide host protection against malaria by reprogramming erythropoiesis through accelerated formation of colony-forming-units-erythroid (CFU-E) cells in the bone marrow. These findings suggest that MSCs are positive regulators of erythropoiesis, making them attractive targets for treatment of malarial anemia. MSC-based therapies, unlike anti-malarial drugs, display therapeutic effects by targeting a large variety of cellular processes rather than a single pathway. In the present review we focus on these recent research findings and discuss clinical applications of MSC-based therapies for malaria. Graphical Abstract: [Figure not available: see fulltext.]