Mesenchymal stromal cells in regenerative medicine: A perspective

Abstract

Multipotent mesenchymal stromal cells (MSCs) of bone marrow origin not only provide a supportive cellular niche for hematopoiesis inside the bone marrow but also differentiate into mesodermal cells such as bone, fat, and cartilage. Clinical uses of culture-expanded MSCs were originally investigated for their presumed hematopoietic-supportive activities. Their use in the clinic was later expanded to the treatment of steroid-resistant acute graft-versus-host disease based on unique immunomodulatory properties shown in a variety of in vitro experiments and in vivo models. Systemically administered MSCs participate in tissue regeneration through diverse biological activities, including paracrine effects that are not necessarily dependent on cell engraftment. Although there is an impressive record of safety in clinical trials, most outcomes have been assessed in the short term, and their efficacy has yet to be shown conclusively in randomized controlled trials. Forty years after their original description and 20 years after their use in humans, culture-expanded MSCs, and particularly their in vivo counterparts, remain poorly understood. However, unless or until better therapeutic options for debilitating disorders are found, the notion that MSCs could be potentially useful warrants further investigation to establish long-term safety and efficacy in well-designed clinical trials.