Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Abstract

Mesenchymal stem cells (MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produce a large number of soluble and membrane-bound factors, some of which inhibit immune responses. However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. The present review describes the large body of literature that has been accumulated on the fascinating biology of MSCs and their complex effects on immune responses.

Mucosally transplanted mesenchymal stem cells stimulate intestinal healing by promoting angiogenesis

“…Despite promising outcomes in animal and early clinical trials, the majority of intravenously injected MSCs became trapped in the lung, limiting their ability as tissue stem cells (5,6). Now, the main mechanism of how transplanted MSCs function is considered to be secretion of proregenerative and antiinflammatory factors (3,4,6,7). While MSCs secrete several antiinflammatory factors that can act at a long distance (e.g., IL-10 and antiinflammatory protein TSG-6), they also produce several factors that are short-lived in the bloodstream (e.g., VEGF-A and prostaglandins) (4).…”

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

“…In this regard, stem cells have become an increasingly plausible mode of therapy for ischemic tissues, mainly due to their immunogenic and angiogenic reparative properties (10)(11)(12).…”

Stem cells and Bronchopulmonary Dysplasia - The five questions: Which cells, when, in which dose, to which patients via which route?

“…Although this approach is very promising, it is still in its infancy. We also have to consider that stem cells encourage the growth and even supplement (host) cells [48]. Additionally, the immunomodulation potential of MSCs may depend on the bidirectional communication between the injured host cells and the graft [49].…”