Extracellular Vesicle Therapy as a Treatment for Osteoarthritis
The clinical community practicing first generation stem cell therapies is slowly shifting away from cell transplants towards harvesting extracellular vesicles from cell in culture and transplanting the vesicles instead. In most cases near all transplanted stem cells die, and that the majority of the effects of such therapies in age-related disease - largely reliable suppression of chronic inflammation rather than improved regeneration of tissues - are mediated by the signaling produced by those cells in the short time that they survive in the recipient. Much of cell signaling is carried within vesicles, and to date the evidence suggests that vesicle therapies produce similar results to stem cell therapies, while being an easier proposition from the logistics perspective.
Age is the most important risk factor for degenerative diseases such as osteoarthritis (OA). It is associated with the accumulation of senescent cells in joint tissues that contribute to the pathogenesis of OA, in particular through the release of senescence-associated secretory phenotype (SASP) factors. Mesenchymal stromal cells (MSCs) and their derived extracellular vesicles (EVs) are promising treatments for OA. However, the senoprotective effects of MSC-derived EVs in OA have been poorly investigated.
Here, we used EVs from human adipose tissue-derived MSCs (ASC-EVs) in two models of inflammaging (IL1β)- and DNA damage (etoposide)-induced senescence in OA chondrocytes. We showed that the addition of ASC-EVs was effective in reducing senescence parameters, including the number of SA-β-Gal-positive cells, the accumulation of γH2AX foci in nuclei and the secretion of SASP factors. In addition, ASC-EVs demonstrated therapeutic efficacy when injected into a murine model of OA. Several markers of senescence, inflammation, and oxidative stress were decreased shortly after injection likely explaining the therapeutic efficacy. In conclusion, ASC-EVs exert a senoprotective function both in vitro, in two models of induced senescence in OA chondrocytes and, in vivo, in the murine model of collagenase-induced OA.
Interesting study. It will be a while before extracellular vesicles take off, even the autologous variety. Medicine is quite slow.
In the meantime, it is of note that Mesoblast's mesenchymal stem cell offering (Ryoncil) has just received FDA approval after its second phase 111 application, so it is all set to go. It will be used for GVHD ( graft versus host disease) which is tha awful sequel to most bone marrow transplants and is why the number of BMT's has gone nowhere for the last 30 years.
Initially, for childhood leukaemia. License extension is expected and no essential reason why all leukaemia should not also be thus treated.
As for ageing, there is little of mention of that but the same drug is already licenced in Japan though not used for that indication AFAIK.
Mesoblast also has another stem cell offering in phase 111 for low back pain. Seems logical that it could be used in any joint eg knee.