Omega-3 polyunsaturated fatty acids promote angiogenesis in placenta derived mesenchymal stromal cells.

Enhancement of angiogenesis is solicited in wound repair and regeneration. Mesenchymal stromal cells derived from the placenta (P-MSCs) have an inherent angiogenic potential. Polyunsaturated fatty acids (PUFAs) in turn, specifically the omega-3 (N-3) are essential for growth and development. They are also recommended as dietary supplements during pregnancy. We therefore hypothesized that addition of N-3 PUFAs in P-MSC culture media may enhance their angiogenic potential. Hence, we treated P-MSCs with omega-3 (N-3) fatty acids -Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) at different concentrations and tested their angiogenic potential. We saw an upregulation of both bFGF and VEGFA. We also found enhanced in vitro tube formation ability of P-MSCs treated with DHA: EPA. We then looked at the influence of the conditioned medium (CM) collected from P-MSCs exposed to DHA: EPA on the key effector cells -HUVECs (Human Umbilical Vein derived endothelial cells and their functionality was further confirmed on chick yolk sac membrane. We found that the CM of P-MSCs exposed to DHA: EPA could enhance angiogenesis in both cases. These result were finally validated in an in vivo matrigel plug assay which revealed enhanced migration and vessel formation in CM treated with DHA: EPA. Our data thus reveals for the first time that supplementation with lower concentration of PUFA enhances the angiogenic potential of P-MSCs making them suitable for chronic wound healing applications.

The anti diabetic and anti obesity effect of Memecylon umbellatum extract in high fat diet induced obese mice.

In recent years, obesity and diabetes have become the epidemic mainly due to fast food and lifestyle changes. Several herbs have been claimed to control diabetes and obesity. However, there are a few which control both. Our aim was to evaluate the anti-diabetic and anti-obesity activity of methanolic extract of Memecylon umbellatum (MU) in alleviation of insulin resistance (IR). Diet induced obese (DIO) mice model was developed by feeding the mice on high fat diet (HFD) for 10 weeks resulting in hyperglycemia, obesity and IR. 250mg/kg body weight of extract was administered orally daily for 8 weeks. Fasting glucose and body weight were monitored throughout the experiment. At the end of the study, serum parameters, histological examinations and gene expression pattern were analyzed. There was a significant reduction in fasting glucose levels, body weight and triglycerides. Improvement in the glucose tolerance and amelioration of insulin resistance was observed as revealed by reduction in serum IL6, serum oxidised LDL, histological sections of liver and subcutaneous adipose. Gene expression studies demonstrated the anti-inflammatory activity of the extract by down regulating IL6, PAI1 and ApoB gene expression as compared to the untreated HFD control. Our results demonstrate for the first time that oral administration of methanolic extract of MU in DIO mice leads to reduction in hyperglycemia, body weight, triglycerides and ameliorates insulin resistance. Further, mechanism of action of the extract needs to be investigated by purifying the extract and analyzing the active ingredient playing the major role.

Can yoga therapy stimulate stem cell trafficking from bone marrow?

It has been established that mesenchymal stromal cells (MSCs) from bone marrow enter the peripheral circulation intermittently for possible tissue regeneration, repair and to take care of daily wear and tear. This is evident from the detection of MSCs from peripheral blood. The factors governing this migration remain elusive. These MSCs carry out the work of policing and are supposed to repair the injured tissues. Thus, these cells help in maintaining the tissue and organ homeostasis. Yoga and pranayama originated in India and is now being practiced all over the world for positive health. So far, the chemical stimulation of bone marrow has been widely used employing injection of colony stimulating factor. However, the role of physical factors such as mechanical stimulation and stretching has not been substantiated. It is claimed that practicing yoga delays senescence, improves the physiological functions of heart and lung and yoga postures make the body elastic. It remains to be seen whether the yoga therapy promotes trafficking of the stem cells from bone marrow for possible repair and regeneration of worn out and degenerating tissues. We cover in this short review, mainly the role of physical factors especially the yoga therapy on stem cells trafficking from bone marrow.

A Small Molecule Swertisin from Enicostemma littorale Differentiates NIH3T3 Cells into Islet-Like Clusters and Restores Normoglycemia upon Transplantation in Diabetic Balb/c Mice.

Aim. Stem cell therapy is one of the upcoming therapies for the treatment of diabetes. Discovery of potent differentiating agents is a prerequisite for increasing islet mass. The present study is an attempt to screen the potential of novel small biomolecules for their differentiating property into pancreatic islet cells using NIH3T3, as representative of extra pancreatic stem cells/progenitors. Methods. To identify new agents that stimulate islet differentiation, we screened various compounds isolated from Enicostemma littorale using NIH3T3 cells and morphological changes were observed. Characterization was performed by semiquantitative RT-PCR, Q-PCR, immunocytochemistry, immunoblotting, and insulin secretion assay for functional response in newly generated islet-like cell clusters (ILCC). Reversal of hyperglycemia was monitored after transplanting ILCC in STZ-induced diabetic mice. Results. Among various compounds tested, swertisin, an isolated flavonoid, was the most effective in differentiating NIH3T3 into endocrine cells. Swertisin efficiently changed the morphology of NIH3T3 cells from fibroblastic to round aggregate cell cluster in huge numbers. Dithizone (DTZ) stain primarily confirmed differentiation and gene expression studies signified rapid onset of differentiation signaling cascade in swertisin-induced ILCC. Molecular imaging and immunoblotting further confirmed presence of islet specific proteins. Moreover, glucose induced insulin release (in vitro) and decreased fasting blood glucose (FBG) (in vivo) in transplanted diabetic BALB/c mice depicted functional maturity of ILCC. Insulin and glucagon expression in excised islet grafts illustrated survival and functional integrity. Conclusions. Rapid induction for islet differentiation by swertisin, a novel herbal biomolecule, provides low cost and readily available differentiating agent that can be translated as a therapeutic tool for effective treatment in diabetes.

Curcumin treatment enhances islet recovery by induction of heat shock response proteins, Hsp70 and heme oxygenase-1, during cryopreservation.

Limited recovery of islets post-cryopreservation influences graft survival and transplantation efficiency during diabetes treatment. As curcumin, a potent antioxidant/radical scavenging compound, protects islets against beta cell toxins, we hypothesized that inclusion of curcumin during cryopreservation or during post-thaw culture or both may rescue islets from cryoinjury. To test the effect of curcumin inclusion on islet recovery murine islets were isolated by the collagenase digestion, cultured for 48 h, cryopreserved using dimethylsulphoxide as cryoprotectant -- with or without curcumin (10 microM) -- and then slow cooled to -40 degrees C before immersing them in liquid nitrogen for 7 days. Following rapid thawing with sucrose gradient and 24 h post-thaw culture -- in presence or absence of curcumin (10 microM) -- islet viability and functionality were determined. Islet recovery in curcumin treated groups was significantly higher than in groups where islets were cryopreserved without curcumin. Islets cryopreserved with curcumin also showed more intact islets as well as better morphology as compared to islets cryopreserved without curcumin. Curcumin treated islets also showed significant inhibition of ROS generation as compared to islets cryopreserved without curcumin. Glucose responsiveness and insulin secretion in islets cryopreserved with curcumin was equal to that of the freshly isolated islets as against islets cryopreserved without curcumin. Elevated level of Hsp 70 and HO-1 were observed in islets cryopreserved with curcumin and may contribute to curcumin-induced islet rescue. Hence, we conclude that inclusion of curcumin into cryopreservation medium inhibits ROS generation and corresponding islet damage and dysfunction.

Autologous bone marrow transplantation/mobilization: a potential regenerative medicine for systemic degenerative disorders and healthy living.

Increased longevity is compromised for the quality of life due to prevalence of metabolic derangements and systemic degenerative disorders, as a result of lifestyle changes in modern days. In a craze to improve upon quality of life, use of pharmacological formulations aimed towards symptomatic treatment regimen is mandatory to manage variety of prevailing human ailments. However; these medicines have their own limitations and side effects, soliciting alternative therapy for better living. In light of preclinical and clinical studies on adult stem cells, bone marrow transplantation in healthy elderly individuals is likely to promote rejuvenation and prevent onset of degenerative disorders as well as cure prevailing disorders if any. Progress in unraveling pleuripotency of adult bone marrow stem cells compelled us to hypothesize that the only way to regain lost cells is to replace them with cells following the principle of 'Like begets Like' which may be achieved by autologous bone marrow transplantation/mobilization.