Biology and clinical trials of human placenta-derived mesenchymal stromal cells (#127)
Mesenchymal stromal cells (MSCs) are derived from rare mesenchymal stem cells. MSCs are present in every vascularised organ in the body since they form part of the endothelium. For use in laboratory experiments or clinical trials, MSCs need to be ex vivo expanded. This is readily achieved by their adherence to plastic. We compared human bone marrow-derived MSCs with human term placenta-derived MSCs and found them very similar in terms of cell surface phenotype, mesodermal lineage differentiation ability and capacity to suppress T cell alloreactivity in a mixed lymphocyte reaction in vitro. MSCs exert their therapeutic benefit in at least four different ways: differentiation into osteoblasts which produce osteoid material to heal non-union bone fractures; paracrine secretion of immune modulatory proteins to minimise exuberant inflammation in infarcted myocardium; transfer of MSC mitochondria to acutely injured pulmonary cells; and apoptosis of T cells in autoimmune disease. We have initiated two clinical trials using placenta-derived MSCs. The first is in patients with idiopathic pulmonary fibrosis. The first cohort of 4 patients have been infused intravenously with 1 x 106 MSCs/kg. No serious adverse events have occurred related to the MSCs. Early results are encouraging and permission has been given by the Data Safety Monitoring Committee to proceed to the next dose-level cohort. The second trial is in patients with treatment-refractory Achilles tendinopathy. The first cohort of 3 patients have been injected with MSCs intratendinously with 1 x 106 MSCs. Again, no serious adverse events have occurred related to the MSCs, and early results are also encouraging. Permission has been given by the Data Safety Monitoring Committee to proceed to the next dose-level cohort. We plan to expand our clinical trial program to a wider range of disease settings. MSCs appear to represent a useful first building block in the regenerative medicine revolution.