While degenerative diseases are not limited to the aged, they do impact them the strongest, with a corresponding economic impact on society. The therapeutic use of stem cells to treat degenerative diseases or ageing has the potential to benefit large groups of people. Somatic stem cells possess the ability to self-renew and differentiate into multiple cell types of the tissue of their location. The ENDOSTEM project had the ambitious goal of advancing new strategies for in situ stimulation of stem cells resident in damaged tissue. Fifteen research and clinical teams from academia, small biotech and large pharmaceutical companies joined efforts to activate muscle stem cells for efficient tissue repair. Running for five years, the project initiated the development of several therapeutics that act on stem cell activation. These therapeutics include nucleic acids, peptides, anti-oxidant drugs and epigenetic modifiers. Following pre-clinical studies on selected compounds, several reached clinical testing. Examples are phase I and II clinical trials for combination of nitric oxide and nonsteroidal anti-inflammatory drugs, a phase II trial evaluating the effects of histone deacetylase inhibitors in Duchenne muscular dystrophy, and a phase II clinical trial using N-acetyl cysteine as a therapeutic agent. In addition, another compound, a soluble for Cripto, emerged directly from the consortium's work and is in an advanced pre-clinical development. ENDOSTEM also investigated the molecular mechanisms for control of stem cell activation and differentiation. The scientists identified several compounds (peptides or miRNA) that improve stem cell migration and recruitment during regeneration. While focusing on muscle regeneration, ENDOSTEM project results facilitate the development of novel cures for other degenerative diseases, including atherosclerosis, vascular damage in diabetes and peripheral ischaemic vascular disease.
Stem cell, degenerative diseases, tissue repair, muscular dystrophy, muscle regeneration