Narrow Results

Anti-fibrotic and tissue regenerative mesenchymal stromal cell (MSC) properties are largely mediated by secreted cytokines and growth factors. MSCs are implanted to augment joint cartilage replacement and to treat diabetic ulcers and burn injuries simultaneously with local anesthetics, which reduce pain. However, the effect of anesthetics on therapeutic human MSC secretory function has not been evaluated. In order to assess the effect of local anesthetics on the MSC secretome, a panel of four anesthetics with different potencies — lidocaine, procaine, ropivacaine and bupivacaine — was evaluated. Since injured tissues secrete inflammatory cytokines, the effects of anesthetics on MSCs stimulated with tumor necrosis factor (TNF)-α and interferon (IFN)-γ were also measured. Dose dependent and anesthesia specific effects on cell viability, post exposure proliferation and secretory function were quantified using alamar blue reduction and immunoassays, respectively. Computational pathway analysis was performed to identify upstream regulators and molecular pathways likely associated with the effects of these chemicals on the MSC secretome. Our results indicated while neither lidocaine nor procaine greatly reduced unstimulated cell viability, ropivacaine and bupivacaine induced dose dependent viability decreases. This pattern was exaggerated in the simulated inflammatory environment. The reversibility of these effects after withdrawal of the anesthetics was attenuated for TNF-α/IFN-γ-stimulated MSCs exposed to ropivacaine and bupivacaine. In addition, secretome analysis indicated that constitutive secretion changes were clearly affected by both anesthetic alone and anesthetic plus TNFα/IFNγ cell stimulation, but the secretory pattern was drug specific and did not necessarily coincide with viability changes. Pathway analysis identified different intracellular regulators for stimulated and unstimulated MSCs. Within these groups, ropivacaine and bupivacaine appeared to act on MSCs similarly via the same regulatory mechanisms. Given the variable effect of local anesthetics on MSC viability and function, these studies underscore the need to evaluate MSC in the presence of medications, such as anesthetics, that are likely to accompany cell implantation.

Recent years have observed the development of stem cell therapy, which appeared as promising treatment strategies for various disease conditions. Cell therapies employ stem cells, or cells grown from stem cells, to replace or rejuvenate damaged tissue. Numerous findings have suggested a significant therapeutic advantage with the utilization of cell therapeutic approaches in various neurological disorders including amyotrophic lateral sclerosis, various heart disorders involving endstage ischaemic heart diseases, myocardial infarction, or preventing vascular restenosis. Various bone fractures are also reported to benefit from cell therapy including osteogenesis imperfecta. Nonetheless, cell therapy has its drawbacks, which include the risk of tumorigenesis or immune rejection. The therapy also faces ethical and political controversies besides scientific challenges. Consequently, efforts are made towards the development of stem cell secretome which are the secreted factors produced by the stem cells that are responsible for mediating and modulating stem cells effects in the disease condition. The secretome holds various added advantages: it can be manufactured, freeze-dried, packaged, and transported more easily which is some of the numerous advantages of using secretome over the use of stem cells. Besides, as secretome is free from cells, there is no need to match the donors and recipients to avoid the risk of rejection. For that reason, stem cell-derived secretome is a promising possibility to be used as pharmaceuticals for regenerative medicine. Up till now, there have have been limited clinical trials utilizing secretome in certain disease conditions.