In vivo reprogramming: A new approach for tissue repair in chronic diseases

Medical researchers and biologists have long been fascinated by the possibility of changing the identity of cells, a phenomenon known as cellular plasticity. Now, we know that differentiated cells can be experimentally coaxed to become pluripotent (cellular reprogramming). Recent studies have demonstrated that changes in cell identity are not limited to the laboratory, but also the tissue cells in live organisms are subjected to this process, too (endogenous cellular reprograming). Nowadays “reprogramming technology” has created new opportunities in understanding human chronic diseases, drug discovery, and regenerative medicine. This technology have enabled the generation of various specific cell types including cardiomyocytes, pancreatic beta cell, and neurons, from patient’s cells such as skin fibroblasts. Reprogramming technology provides a novel cell source for autologous cell transplantation. But, cell transplantation faces several difficult hurdles such as cell production and purification, long-term survival, and functional integration after transplantation. Recently, in vivo reprogramming, which uses endogenous cells for tissue repair, has emerged as a new approach to circumvent cell transplantation. Up till now, in vivo reprogramming has been practiced in the mouse pancreas, heart, brain, and spinal cord with various degrees of success. In this review, we summarize the progress made, therapeutic potentials, and the challenges ahead in this emerging research area

In vivo reprogramming: A new approach for tissue repair in chronic diseases

Medical researchers and biologists have long been fascinated by the possibility of changing the identity of cells, a phenomenon known as cellular plasticity. Now, we know that differentiated cells can be experimentally coaxed to become pluripotent (cellular reprogramming). Recent studies have demonstrated that changes in cell identity are not limited to the laboratory, but also the tissue cells in live organisms are subjected to this process, too (endogenous cellular reprograming). Nowadays “reprogramming technology” has created new opportunities in understanding human chronic diseases, drug discovery, and regenerative medicine. This technology have enabled the generation of various specific cell types including cardiomyocytes, pancreatic beta cell, and neurons, from patient’s cells such as skin fibroblasts. Reprogramming technology provides a novel cell source for autologous cell transplantation. But, cell transplantation faces several difficult hurdles such as cell production and purification, long-term survival, and functional integration after transplantation. Recently, in vivo reprogramming, which uses endogenous cells for tissue repair, has emerged as a new approach to circumvent cell transplantation. Up till now, in vivo reprogramming has been practiced in the mouse pancreas, heart, brain, and spinal cord with various degrees of success. In this review, we summarize the progress made, therapeutic potentials, and the challenges ahead in this emerging research area

Cross-talks between the kidneys and the central nervous system in multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease, which is considered as a common autoimmune disorder in young adults. A growing number of evidences indicated that the impairment in non-neural tissues plays a significant role in pathology of MS disease. There are bidirectional relationship, metabolic activities and functional similarity between central nervous system (CNS) and kidneys which suggest that kidney tissue may exert remarkable effects on some aspects of MS disorder and CNS impairment in these patients compels the kidney to respond to central inflammation. Recently, it has been well documented that hormonal secretion possesses the important role on CNS abnormalities. In this regard, due to the functional similarity and significant hormonal and non-hormonal relationship between CNS and kidneys, we hypothesized that kidneys exert significant effect on initiation, progression or amelioration of MS disease which might be regarded as potential therapeutic approach in the treatment of MS patients in the future

Differential Expression of Klotho in the Brain and Spinal Cord is Associated with Total Antioxidant Capacity in Mice with Experimental Autoimmune Encephalomyelitis

Recently, we reported a positive correlation between Klotho, as an anti-aging protein, and the total antioxidant capacity (TAC) in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, there is no information about the Klotho and TAC changes within the central nervous system (CNS). Thus, the current study aimed to employ an experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice using MOG35–55 peptide to examine the relationship between Klotho and TAC within the CNS. To this end, the brain and spinal cord were obtained at the onset and peak stages of EAE as well as non-EAE mice (sham/control groups). The Klotho expression was assessed in the brain and spinal cord of different experimental groups at mRNA (qPCR) and protein (ELISA) levels. Also, TAC level was determined in the tissues of different experimental groups. The results showed that Klotho expression in the brain at the onset and peak stages of EAE were significantly lower than that in non-EAE mice. Conversely, Klotho expression in the spinal cord at the onset of EAE was significantly higher than that of non-EAE mice, while Klotho was comparable at the peak stage of EAE and non-EAE mice. The pattern of TAC alteration in the brain and spinal cord of EAE mice was similar to that of Klotho expression. In conclusion, for the first time, this study demonstrated a significant positive correlation between Klotho and TAC changes during the pathogenesis of EAE. It is suggested that Klotho may have neuroprotective activity through the regulation of redox system

Correlation between Klotho changes and calcium-phosphate concentration in the serum at early stages of multiple sclerosis

BACKGROUND: There are several studies indicating that an anti-aging protein, namely Klotho protein, participates in the regulation of calcium and phosphate metabolism. In addition, we showed that Klotho protein was involved in the pathogenesis of multiple sclerosis (MS). Hence, we hypothesized that Klotho protein changes in patients with multiple sclerosis might lead to alteration of calcium and phosphate metabolism. Accordingly, the aim of the present study was to evaluate the alteration of calcium and phosphate levels together with the concentration of Klotho protein in the serum of patients with multiple sclerosis.METHODS: In this case-control study, 14 patients with newly diagnosed relapsing-remitting multiple sclerosis (RRMS) along with 14 control individuals with noninflammatory neurological disorders were enrolled. The serum concentrations of Klotho protein, calcium, and phosphate were measured in serum of participants using commercial kits. The data were analyzed at the significant level of P < 0.050.RESULTS: There were no significant changes in serum concentrations of Klotho protein, and phosphate in patients with multiple sclerosis when compared to controls. However, the serum calcium concentration was significantly lower than the control group. Regarding patients with multiple sclerosis, there was a significant positive correlation between changes in serum concentrations of Klotho protein and calcium (r = 0.604, P = 0.022), whereas the other correlations were not statistically significant.CONCLUSION: To our knowledge, this is the first study demonstrating a positive correlation between serum concentrations of secretory Klotho protein and calcium in patients with multiple sclerosis