Harvesting extracellular vesicles from cell cultures and then delivering them to patients is a way to obtain the benefits of first generation stem cell therapies with considerably fewer issues that delivery of cells. One doesn't have to worry about compatibility with the patient, for example. Logistically, vesicles are much easier to store, transport, and employ in therapy than cells. Since most of these first generation stem cell therapies achieve near all of their benefits via cell signaling in the short period before the transplanted cells die, the use of vesicles is a practical alternative, and an area in which considerable effort is going towards clinical development and application. Alongside the usual mix of companies working on therapies and researchers running animal studies, such as the one noted here, it is also quite possible for anyone in the US today to arrange extracellular vesicle injections given a little research into providers and a cooperative physician.
Recently, mesenchymal stem cell (MSC) transplantation has shown promising therapeutic potential in alleviating ageing-associated phenotypes. Despite their potential therapeutic applications, the direct use of stem cell transplantation still faces several hurdles, such as the risk of tumorigenesis and undesirable immune responses. Recent evidence has indicated the therapeutic potential of small extracellular vesicles (sEVs) secreted by MSCs derived from different tissues in alleviating cellular senescence, while avoiding the undesirable immune response and the risk of tumorigenesis. However, harvesting MSCs from different tissues, such as the bone marrow and adipose tissue, is invasive. In addition, limitations such as the decreased proliferative potential and therapeutic efficacy of MSCs during in vitro expansion have impeded the industrial production of sEVs.
Induced pluripotent stem cells (iPSCs) are a subpopulation of stem cells that can be reprogrammed from any tissue type in the body. iPSCs have a unique ability to proliferate indefinitely and display totipotency in vitro. Furthermore, induced pluripotent stem cell-derived MSCs (iMSCs) possess MSC-like therapeutic effects in tissue regeneration treatments. Along with the advantages of the acquisition and proliferation of iMSCs, compared with those of MSCs, sEVs can be abundantly obtained from iMSCs, which is convenient for industrial production.
Intervertebral disc degeneration (IVDD) models were established by puncturing discs from the tails of rats. Then, iMSC-sEVs were injected into the punctured discs. The degeneration of punctured discs was assessed. The age-related phenotypes were used to determine the effects of iMSC-sEVs on senescent nucleus pulposus cells (NPCs) in vitro. Western blotting was used to detect the expression of Sirt6. miRNA sequencing analysis was used to find miRNAs that potentially mediate the activation of Sirt6.
After injecting iMSC-sEVs, NPC senescence and IVDD were significantly improved. iMSC-sEVs could rejuvenate senescent NPCs and restore the age-related function by activating the Sirt6 pathway in vitro. Further, microRNA sequence analysis showed that iMSC-sEVs were highly enriched in miR-105-5p, which played a pivotal role in the iMSC-sEV-mediated therapeutic effect by downregulating the level of the cAMP-specific hydrolase PDE4D and could lead to Sirt6 activation. In conclusion, iMSC-sEVs could rejuvenate the senescence of NPCs and attenuate the development of IVDD.