Abstract
The therapeutic repertoire for life-threatening inflammatory conditions like sepsis, graft-versus-host reactions, or colitis is very limited in current clinical practice and, together with chronic ones, like the osteoarthritis, presents growing economic burden in developed countries. This urges the development of more efficient therapeutic modalities like the mesenchymal stem cell-based approaches. Despite the encouraging in vivo data, however, clinical trials delivered ambiguous results. Since one of the typical features of inflamed tissues is decreased oxygenation, the success of cellular therapy in inflammatory pathologies seems to be affected by the impact of oxygen depletion on transplanted cells. Here, we examine our current knowledge on the effect of hypoxia on the physiology of bone marrow-derived mesenchymal stromal cells, one of the most popular tools of practical cellular therapy, in the context of their immune-modulatory capacity.
Highlights
Mesenchymal stromal cells (MSCs) are considered to be a promising tool for cellular therapy in various human pathologies
Since differential oxygen levels exert complex effects on cellular physiology, here, we review our current understanding on the interplay between the immune-modulatory effects and hypoxic response of Bone marrow-derived MSCs (BMSCs) and formulate problems to be addressed in order to develop more efficient BMSC-based medical applications for inflammatory pathologies
BMSCs have been tried in a number of human pathologies that exert immune dysfunction or imbalance of the regulation of immune response where our current therapeutic repertoire is very limited
Summary
Mesenchymal stromal cells (MSCs) are considered to be a promising tool for cellular therapy in various human pathologies. These include both chronic and acute inflammatory conditions like, for instance, osteoarthritis, rheumatoid arthritis, colitis, septic conditions, or graft-versus-host disease. Behind the diverse pathogenesis of the distinct inflammatory conditions, local hypoxia is considered to be a common pathogenic factor. Bone marrow-derived MSCs (BMSCs) naturally reside in a severely oxygen-depleted microenvironment that supports the concept of their use in the cellular therapy of inflammatory conditions [1, 2]. Since differential oxygen levels exert complex effects on cellular physiology, here, we review our current understanding on the interplay between the immune-modulatory effects and hypoxic response of BMSCs and formulate problems to be addressed in order to develop more efficient BMSC-based medical applications for inflammatory pathologies
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