THE CONCEPT OF MESENCHYMAL STEM CELLS: FROM THEIR DISCOVERY TO INNOVATIVE MSC-DERIVED THERAPIES

Bruno Delorme

R&D Director of Macopharma Corp., France

Abstract

With more than 500 ongoing clinical trials, mesenchymal stem cells (MSC) represent a widely used and very attractive stem cell candidate for the treatment of a broad range of diseases. From the discovery of bone marrow (BM) MSCs, we will summarize the historical landmarks that lead to the progressive understanding of MSC biology. We will describe their stem cell attributes in terms of phenotypic identity, proliferation capacity, self-renewal, multipotentiality, plasticity, homing, mobilisation in peripheral blood, and tissue regeneration. We will highlight the specific lineage-priming of BM-MSC that provide the molecular framework for their plasticity. By comparing MSC with the paradigmatic hematopoietic stem cell, we will postulate that MSC may constitute another paradigm for stem cell systems where plasticity represent the major characteristic. Because of the scarcity of the MSC in the tissues, clinical grade ex vivo expansion of MSC is necessary for their use in clinic. Their classification as “ATMP” in Europe and the US FDA requirements necessitate a manufacturing process and quality controls following Good Manufacturing Practices. The challenging compliance with such pharmaceutical-like standards will be discussed. New avenues are now exploring cell-free MSC-derived strategies based on the use of secreting paracrine factors and/or extracellular exosomes.