Abstract
Present in numerous tissues, mesenchymal stem cells/multipotent stromal cells (MSCs) can differentiate into different cell types from a mesoderm origin. Their potential has been extended to pluripotency, by their possibility of differentiating into tissues and cells of nonmesodermic origin. Through the release of cytokines, growth factors and biologically active molecules, MSCs exert important paracrine effects during tissue repair and inflammation. Moreover, MSCs have immunosuppressive properties related to non-HLA restricted immunosuppressive capacities. All these features lead to an increasing range of possible applications of MSCs, from treating immunological diseases to tissue and organ repair, that should be tested in phase I and II clinical trials. The most widely used MSCs are cultured from bone marrow or adipose tissue. For clinical trial implementation, BM MSCs and ADSCs should be produced according to Good Manufacturing Practices. Safety remains the major concern and must be ensured during culture and validated with relevant controls. We describe some applications of MSCs in clinical trials.
Highlights
From the end of the 1960s to the beginning of the 1970s, a Soviet scientist, Alexander Friedenstein, discovered a population of adherent cells in bone marrow (BM) that could differentiate into osteoblasts, chondrocytes, and hematopoietic stromal supportive cells [1]
The stemness status and the long-term self-renewal potential of mesenchymal stem cells (MSCs) has not been definitely established, so the preferred term is multipotent mesenchymal stromal cells [3], both terms being abbreviated to MSCs
We report on the current experience in the use of MSCs and adipose-derived stromal cells (ADSCs)
Summary
From the end of the 1960s to the beginning of the 1970s, a Soviet scientist, Alexander Friedenstein, discovered a population of adherent cells in bone marrow (BM) that could differentiate into osteoblasts, chondrocytes, and hematopoietic stromal supportive cells [1]. Cultured MSCs are a mix of cells ranging from progenitors to mature stromal cells. Besides their differentiation potential, MSCs have an immunosuppressive effect both in vitro and in vivo by acting on all immune effectors [4]. MSCs have consistent trophic effects mediated by the wide range of growth factors and cytokines they produce [5] These biological properties of MSCs rapidly led to investigation of their use in cell-based therapy by the middle of the 1990s. We report on the current experience in the use of MSCs and ADSCs. First we discuss culture requirements and safety concerns, and describe several ongoing clinical trials
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