We have to remember that MSC differentiation into undesired tissues has been reported as well. This makes crucially necessary the acquisition of strong Gilenya biological knowledge about the behaviour and differentiation program of these cells, before any clinical trial could be performed in humans.47 Kidney repair Different adult stem cells have been shown to differentiate into mature kidney cells, opening the question whether post-natal stem cells may be a potential tool for renal repair after systemic administration. Some studies in different models of kidney injury have suggested a role of resident bone marrow stem cells in kidney repair.48,49 Poulsom et al50 showed in mice that, after receiving bone marrow transplantation, circulating stem cells could be recruited to the site of injury overcoming acute kidney failure.
Since the bone marrow (BM) contains at least a couple of known stem cell populations, haematopoietic stem cells (HSCs) and MSCs, these last ones may be responsible for improvement in a renal damage scenario, even though it remains unclear the actual number of MSCs in the adult kidney and whether they would be the only sufficient population of stem cells involved in the recovery. Despite the discrepancies about the mechanism, MSCs have been reported to protect against chemical-induced toxicity (cisplatin and glycerol) in mice, and in case of glycerol, MSC mobilization into the damaged kidney seemed to be dependent on the presence of CD44. Kidneys damaged by injection of glycerol overexpressed hyaluronic acid (HA) and MSCs isolated from mice lacking CD44, the receptor for HA, were unable to migrate to injured sites of the kidneys.
51,52 On the contrary, other chronic disease models showed no association between MSCs and improvement in renal function and/or animal survival.53 Nevertheless, additional knowledge about MSC transmigration mechanisms and differentiation into renal cells is required in order to consider MSCs as a future cellular source for kidney repair. Joint regeneration in rheumatic diseases Joint degeneration usually comes as a parallel event to degenerative arthritis (osteoarthritis, OA) or rheumatoid arthritis (RA). Like other autoimmune diseases, they develop as a result of immunologic instability and loss of tolerance. Then, the immune system starts to react against self structures and tissues of the organism leading to gradual reduction of extracellular matrices in joint cartilage and bone.
In these cases, therapy is focused in alleviating symptoms and/or changing the disease progress but never restores AV-951 joint structure and functionality. Moreover, resistance for conventional therapy of anti-inflammatory and immunosuppressive drugs has been reported in some patients, making necessary the use of extremely high doses which are normally associated to side effects. Therefore, in these particular cases, BM restoration is recommended.