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During the past decade, numerous studies in animal models and clinical trials explored the potential of MSCs in the treatment of diseases associated with tissue regeneration and inflammatory control. Other qualities of MSCs: ready accessibility in bone marrow and fat tissue and rapid expansion in culture make the therapeutic use of patients\u2019 own cells feasible. The prevailing belief that MSCs are nonimmunogenic encouraged the use of unrelated donor cells in immune-competent recipients. The data emerging from studies performed with immune-incompatible cells in animal models for a wide-range of human diseases show, however, conflicting results and cast doubt on the immune privileged status of MSCs. Our analysis of the preclinical literature in this review is aimed to gain a better understanding of the therapeutic potential of immune-incompatible MSCs. Emphasis was laid on applications for enhancement of tissue repair in the absence of immune-suppressive therapy. 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