Investigation of the differentiation potential of pericyte cells as an alternative source of mesenchymal stem cells.

BACKGROUND: The mesenchymal stem cells (MSCs) with characterized by their multipotency and capacity to differentiate into various tissue cell types, have led to their incorporation in regenerative medicine research. However, the limited numbers of MSCs in the human body and their diverse differentiation capabilities in tissues highlight the need for exploring alternative regenerative cell sources. In this study, therefore, we conducted molecular level examinations to determine whether pericytes, specialized cell communities situated near blood vessels, could serve as a substitute for human bone marrow-derived mesenchymal stem cells (hBM-MSCs). In this context, the potential application of pericytes surrounds the vessels when MSCs are insufficient for functional purposes. METHODS: The pericytes utilized in this investigation were derived from the placenta and characterized at the third passage. Similarly, the hBM-MSCs were also characterized at the third passage. The pluripotent properties of the two cell types were assessed at the gene expression level. Thereafter, both pericytes and hBM-MSCs were directed towards adipogenic, osteogenic and chondrogenic differentiation. The cells in both groups were examined on days 7, 14, and, 21 and their differentiation status was compared both immunohistochemically and through gene expression analysis. RESULTS: Upon comparing the pluripotency characteristics of placental pericytes and hBM-MSCs, it was discovered that there was a substantial upregulation of the pluripotency genes FoxD3, Sox2, ZPF42, UTF1, and, Lin28 in both cell types. However, no significant expression of the genes Msx1, Nr6a1, Pdx1, and, GATA6 was observed in either cell type. It was also noted that pericytes differentiate into adipogenic, osteogenic and, chondrogenic lineages similar to hBM-MSCs. DISCUSSION: As a result, it has been determined that pericytes exhibit high differentiation and proliferation properties similar to those of MSCs, and therefore can be considered a suitable alternative cell source for regenerative medicine and tissue engineering research, in cases where MSCs are not available or insufficient. It is notable that pericytes have been suggested as a potential substitute in studies where MSCs are lacking.

Resveratrol prevents cognitive deficits by attenuating oxidative damage and inflammation in rat model of streptozotocin diabetes induced vascular dementia.

Diabetes is one of the risk factors for the development of vascular dementia (VD), leading to endothelial dysfunction and cognitive impairment. Resveratrol has been shown to have antioxidant, antiinflammatory, and neuroprotective effects. The previous studies have also reported that resveratrol improves cognitive and vascular endothelial functions in several pathological conditions. In the present study we aimed to evaluate the effect of resveratrol on cognitive and vascular endothelial function and to explore the mechanisms of its effects in the streptozotocin-induced diabetic rat model of VD. Male Wistar rats were divided into 3 groups (n = 10 in each group): Control, diabetes (DM), DM + resveratrol (DM + RSV) groups. Rats from the DM + RSV group received resveratrol (20 mg/kg/day, ip) for 4 weeks after induction of diabetes and then cognitive functions of the rats were tested by the Morris water maze and a passive avoidance tests. After behavioral tests, endothelial function of thoracic aorta (the endothelium-dependent and -independent vasorelaxant responses) was investigated. To explore the mechanisms of resveratrol, endothelial eNOS, aortic superoxide dismutase (SOD), NADPH oxidase, heme oxygenase-1 (HO-1) levels, TNF-α and IL-1ß expressions; serum SOD and NADPH oxidase levels and, hippocampal BDNF, TNF-α and IL-1ß expressions were measured. It was shown that DM resulted in severe learning and memory deficits associated with endothelial dysfunction, increased expression of TNF-α and IL-1ß, increased oxidative stress levels and decreased expression of eNOS and BDNF. In contrast, resveratrol treatment improved the cognitive decline. It was also found that chronic treatment with resveratrol ameliorated the impaired vascular reactivity. Reveratrol significantly reversed diabetes-induced changes of protein expression. Our data suggest that resveratrol prevents memory deficits, endothelial dysfunction, increased oxidative stress, inflammation and impairment of neurotrophin expression in a VD rat model. Thus, the vasculoprotective and neuroprotective effects of resveratrol may be beneficial in DM patients.

Improvement of the insulin secretion from beta cells encapsulated in alginate/poly-L- histidine/alginate microbeads by platelet-rich plasma.

Type 1 diabetes is clinically characterized as the loss of control of glucose homeostasis due to the reduced number of insulinproducing cells. Long-term glycemic control after implantation could be maintained by preserving the cell viability and tissue-specific functions during the process of microencapsulation. In this study, alginate solution was supplemented with platelet-rich plasma (PRP) to improve the viability and preserve the cell functions during the encapsulation of a beta cell line (BRIN-BD11). Cell viability was assessed and insulin secretion and insulin stimulation index were evaluated. eTh polymerization of alginate with PRP enhanced the viability up to 61% in the alginate microbeads. PRP supplementation to the alginate composition not only increased the number of viable cells by 1.95-fold, but the insulin secretion also improved by about 66%. eTh stimulation index, however, was not affected by the PRP supplementation.

Evaluation of DNA damage after tourniquet-induced ischaemia/reperfusion injury during lower extremity surgery.

Ischemia/reperfusion (I/R) injury represents a source of substantial morbidity and mortality in various statuses that is, coronary bypass, myocardial infarction, and so on. Oxygen free radicals, formed during I/R, have been proposed as one of the main causes of tissue injury and play important role in I/R injury. Leucocytes have been shown to play an important role in the development of tissue injury after I/R. Accordingly, numerous studies have shown that even short-time I/R-induced DNA damage can be investigated in human peripheral leucocytes using the alkaline single-cell gel-electrophoresis assay (comet assay). After ischaemia, the genotoxic damage detected in human peripheral leucocytes locally in the reperfused tissue results in numerical, morphologic and biochemical alterations of all circulating white blood cells in the human organism. It leads particularly to the release of substantial amounts of oxygen radicals and other reactive agents. Simultaneously, local ischaemia in the reperfused tissue is extended to the whole body systemically through these activated inflammatory cells and, possibly, results in secondary detectable tissue damage in endothelial cells of the systemic circulation inducing prolonged DNA damage even in the early reperfusion period. Thus, we aimed to investigate whether the I/R during the routinely practised operation causes DNA damage, since other published studies were on animal and in vitro models and did not exactly reflect the operation procedure in the clinic. We measured DNA damage (single-strand breaks, oxidised purines and pyrimidines) by modified alkaline comet assay using two bacterial enzymes (formamidopyrimidine glycosylase (Fpg), endonuclease III (EndoIII)), which recognise oxidised purines and pyrimidine bases, in patients who had lower extremity surgery. There was no statistically significant difference in DNA damage between time periods (before surgery, after I/R; T1, T2 and T3). According to our findings, we indicate that at the molecular level DNA is damaged due to the I/R during the routinely practised operation; however, this effect could not be determined phenotypically. Thus, we may suggest that the surgeons and anaesthetist/operation room personnel could be informed about that fact and encouraged to use antioxidants and/or apply prophylaxis. Our findings showed that I/R injury did not induce DNA damage. Further studies of this approach are needed.