Manipal Institute of Regenerative Medicine

Bangalore, India

Manipal Institute of Regenerative Medicine

Bangalore, India
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Sunil V.,University Graduate Center | Shree N.,Manipal Institute of Regenerative Medicine | Venkataranganna M.V.,Connexios Life science | Bhonde R.R.,Manipal Institute of Regenerative Medicine | Majumdar M.,University Graduate Center
Biomedicine and Pharmacotherapy | Year: 2017

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. 250 mg/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. © 2017 Elsevier Masson SAS


Gupta A.K.,Molecular Biology Unit | Gupta A.K.,North West University | Rastogi G.,University of California at Davis | Rastogi G.,Wetland Research and Training Center | And 5 more authors.
Medical and Veterinary Entomology | Year: 2014

Flesh flies of the genus Sarcophaga (Diptera: Sarcophagidae) are carrion-breeding, necrophagous insects important in medical and veterinary entomology as potential transmitters of pathogens to humans and animals. Our aim was to analyse the diversity of gut-associated bacteria in wild-caught larvae and adult flesh flies using culture-dependent and culture-independent methods. Analysis of 16S rRNA gene sequences from cultured isolates and clone libraries revealed bacteria affiliated to Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes in the guts of larval and adult flesh flies. Bacteria cultured from larval and adult flesh fly guts belonged to the genera Acinetobacter, Bacillus, Budvicia, Citrobacter, Dermacoccus, Enterococcus, Ignatzschineria, Lysinibacillus, Myroides, Pasteurella, Proteus, Providencia and Staphylococcus. Phylogenetic analysis showed clone sequences of the genera Aeromonas, Bacillus, Bradyrhizobium, Citrobacter, Clostridium, Corynebacterium, Ignatzschineria, Klebsiella, Pantoea, Propionibacterium, Proteus, Providencia, Serratia, Sporosarcina, Weissella and Wohlfahrtiimonas. Species of clinically significant genera such as Ignatzschineria and Wohlfahrtiimonas spp. were detected in both larvae and adult flesh flies. Sequence analysis of 16S rRNA gene libraries supported culture-based results and revealed the presence of additional bacterial taxa. This study determined the diversity of gut microbiota in flesh flies, which will bolster the ability to assess microbiological risk associated with the presence of these flies. The present data thereby establish a platform for a much larger study. © 2014 The Royal Entomological Society.


Kumar T.S.,Indian Institute of Science | Kari V.,Indian Institute of Science | Choudhary B.,Indian Institute of Science | Choudhary B.,Manipal Institute of Regenerative Medicine | And 3 more authors.
Journal of Biological Chemistry | Year: 2010

Cancer cells are often associated with secondary chromosomal rearrangements, such as deletions, inversions, and translocations, which could be the consequence of unrepaired/misrepaired DNA double strand breaks (DSBs). Nonhomologous DNA end joining is one of the most common pathways to repair DSBs in higher eukaryotes. By using oligomeric DNA substrates mimicking various endogenous DSBs in a cell-free system, we studied end joining (EJ) in different cancer cell lines. We found that the efficiency of EJ varies among cancer cells; however, there was no remarkable difference in the mechanism and expression of EJ proteins. Interestingly, cancer cells with lower levels of EJ possessed elevated expression of BCL2 and vice versa. Removal of BCL2 by immunoprecipitation or protein fractionation led to elevated EJ. More importantly, we show that overexpression of BCL2 or the addition of purified BCL2 led to the down-regulation of EJ. Further, we found that BCL2 interacts with KU proteins both in vitro and in vivo. Hence, our results suggest that EJ in cancer cells could be negatively regulated by the anti-apoptotic protein, BCL2, and this may contribute toward increased chromosomal abnormalities in cancer. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.


Venkatesan V.,National Institute of Nutrition | Gopurappilly R.,Manipal Institute of Regenerative Medicine | Goteti S.K.,National Institute of Nutrition | Dorisetty R.K.,National Institute of Nutrition | Bhonde R.R.,Manipal Institute of Regenerative Medicine
Islets | Year: 2011

The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing β-cells. The functional mass of β-cells is decreased in most forms of diabetes, so replacing missing β-cells or triggering their regeneration may allow for improved diabetes treatment. Therefore, expansion of the β-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding β-cell regeneration. One potential source is the islet proper, via the de-differentiation, proliferation and redifferentiation of facultative progenitors residing within the islet. The new pancreatic islets derived from progenitor cells present within the ducts have been reported, but the existence and identity of the progenitor cells have been debated. In this mini-review, we focus primarily on pancreatic progenitors, which are islet progenitors capable of differentiating into insulin producing cells. We also emphasize the importance of pancreatic progenitors as a target for stem cell therapy for diabetes. ©2011 Landes Bioscience.


Venkatesan V.,National Institute of Nutrition | Chalsani M.,National Institute of Nutrition | Nawaz S.S.,National Institute of Nutrition | Bhonde R.R.,Manipal Institute of Regenerative Medicine | And 2 more authors.
Cytotechnology | Year: 2012

WNIN/Ob, a mutant rat strain, developed at the National Center for Laboratory Animal Sciences (NCLAS) facility of National Institute of Nutrition (NIN), is a new animal model to study the metabolic syndrome. These animals have 47% fat in their body and isolation of islets from these animals were compounded due to the formation of amorphous viscous and jelly like material which reduced the islet yield. However, islets isolated from WNIN adult (≥12 months) control rats gave a good islet recovery, under standard isolation procedures using collagenase digestion. In the present study we optimized culture conditions in WNIN/Ob rats to isolate islets with higher yield, and also established primary islet cell cultures from these mutant rats, retaining cellular integrity and functionality. © 2011 Springer Science+Business Media B.V.


Bhonde R.R.,Manipal Institute of Regenerative Medicine | Sheshadri P.,Manipal Institute of Regenerative Medicine | Sharma S.,Manipal Institute of Regenerative Medicine | Kumar A.,Manipal Institute of Regenerative Medicine
International Journal of Biochemistry and Cell Biology | Year: 2014

Generation of surrogate β-cells is the need of the day to compensate the short supply of islets for transplantation to diabetic patients requiring daily shots of insulin. Over the years several sources of stem cells have been claimed to cater to the need of insulin producing cells. These include human embryonic stem cells, induced pluripotent stem cells, human perinatal tissues such as amnion, placenta, umbilical cord and postnatal tissues involving adipose tissue, bone marrow, blood monocytes, cord blood, dental pulp, endometrium, liver, labia minora dermis-derived fibroblasts and pancreas. Despite the availability of such heterogonous sources, there is no substantial breakthrough in selecting and implementing an ideal source for generating large number of stable insulin producing cells. Although the progress in derivation of β-cell like cells from embryonic stem cells has taken a greater leap, their application is limited due to controversy surrounding the destruction of human embryo and immune rejection. Since multipotent mesenchymal stromal cells are free of ethical and immunological complications, they could provide unprecedented opportunity as starting material to derive insulin secreting cells. The main focus of this review is to discuss the merits and demerits of MSCs obtained from human peri- and post-natal tissue sources to yield abundant glucose responsive insulin producing cells as ideal candidates for prospective stem cell therapy to treat diabetes. © 2013 Elsevier Ltd.


Kadam S.,Indian Institute of Technology Bombay | Govindasamy V.,Manipal Institute of Regenerative Medicine | Bhonde R.,Manipal Institute of Regenerative Medicine
Methods in Molecular Biology | Year: 2012

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been used for allogeneic application in tissue engineering but have certain drawbacks. Therefore, mesenchymal stem cells (MSCs) derived from other adult tissue sources have been considered as an alternative. The human umbilical cord and placenta are easily available noncontroversial sources of human tissue, which are often discarded as biological waste, and their collection is noninvasive. These sources of MSCs are not subjected to ethical constraints, as in the case of embryonic stem cells. MSCs derived from umbilical cord and placenta are multipotent and have the ability to differentiate into various cell types crossing the lineage boundary towards endodermal lineage. The aim of this chapter is to provide a detailed reproducible cookbook protocol for the isolation, propagation, characterization, and differentiation of MSCs derived from human umbilical cord and placenta with special reference to harnessing their potential towards pancreatic/islet lineage for utilization as a cell therapy product. We show here that mesenchymal stromal cells can be extensively expanded from umbilical cord and placenta of human origin retaining their multilineage differentiation potential in vitro. Our report indicates that postnatal tissues obtained as delivery waste represent a rich source of mesenchymal stromal cells, which can be differentiated into functional islets employing three-stage protocol developed by our group. These islets could be used as novel in vitro model for screening hypoglycemics/insulin secretagogues, thus reducing animal experimentation for this purpose and for the future human islet transplantation programs to treat diabetes. © 2012 Springer Science+Business Media, LLC.


Kanafi M.M.,Manipal Institute of Regenerative Medicine | Ramesh A.,Manipal Institute of Regenerative Medicine | Gupta P.K.,Manipal Institute of Regenerative Medicine | Gupta P.K.,Stempeutics Research Pvt. Ltd. | Bhonde R.R.,Manipal Institute of Regenerative Medicine
Cells Tissues Organs | Year: 2013

The therapeutic potential of mesenchymal stromal cells depends on their ability to survive and proliferate under adverse in vivo scenarios in a particular disease. In most of the sites of injury, especially in diabetic wounds, there can be hypoxia, hyperglycemia, and ischemia, leading to a lack of nutrients. Hence, the aim of our present study was to investigate the influence of hypoxia, high glucose, and low serum concentrations on the growth kinetics and proliferative potential of human dental pulp stem cells from exfoliated deciduous teeth (SHED) and permanent teeth (DPSC). In this study we isolated two types of specialized stem cells from human dental pulp tissues, which were supposedly of neural crest origin, and cultured them in KO-DMEM medium supplemented with 10% fetal bovine serum (FBS). Both SHED and DPSC were characterized for standard CD surface markers, and their ability to differentiate into adipogenic and osteogenic lineages was tested. SHED and DPSC were exposed to either hypoxia or high glucose or low serum conditions, and their growth kinetics and differentiation potentials were compared with those of normal culture conditions. We found that SHED retained their phenotypic expression and differentiation potential under hypoxia, high-glucose, and low-serum conditions and exhibited a higher proliferation in terms of cell yield and a reduced doubling time compared to DPSC. Our findings clearly demonstrate for the first time that SHED are superior to DPSC as evidenced by their enhanced proliferation under adverse culture conditions. © 2013 S. Karger AG, Basel.


Ahanger S.H.,National Center for Cell Science | Ahanger S.H.,Justus Liebig University | Gunther K.,Justus Liebig University | Weth O.,Justus Liebig University | And 5 more authors.
Scientific Reports | Year: 2014

Insulator mediated alteration in higher-order chromatin and/or nucleosome organization is an important aspect of epigenetic gene regulation. Recent studies have suggested a key role for CP190 in such processes. In this study, we analysed the effects of ectopically tethered insulator factors on chromatin structure and found that CP190 induces large-scale decondensation when targeted to a condensed lacO array in mammalian and Drosophila cells. In contrast, dCTCF alone, is unable to cause such a decondensation, however, when CP190 is present, dCTCF recruits it to the lacO array and mediates chromatin unfolding. The CP190 induced opening of chromatin may not be correlated with transcriptional activation, as binding of CP190 does not enhance luciferase activity in reporter assays. We propose that CP190 may mediate histone modification and chromatin remodelling activity to induce an open chromatin state by its direct recruitment or targeting by a DNA binding factor such as dCTCF. © 2014, Nature Publishing Group. All rights reserved.


Madhira S.L.,National Institute of Nutrition | Challa S.S.,National Institute of Nutrition | Chalasani M.,National Institute of Nutrition | Nappanveethl G.,National Institute of Nutrition | And 3 more authors.
PLoS ONE | Year: 2012

Background: Development of model systems have helped to a large extent, in bridging gap to understand the mechanism(s) of disease including diabetes. Interestingly, WNIN/GR-Ob rats (Mutants), established at National Centre for Laboratory Animals (NCLAS) of National Institute of Nutrition (NIN), form a suitable model system to study obesity with Type 2 diabetes (T2D) demonstrating several secondary complications (cataract, cardiovascular complications, infertility, nephropathy etc). The present study has been carried out to explore the potent application(s) of multipotent stem cells such as bone marrow mesenchymal stem cells (BM-MSCs), to portray features of pre-diabetic/T2D vis-à-vis featuring obesity, with impaired glucose tolerance (IGT), hyperinsulinemia (HI) and insulin resistance (IR) seen with Mutant rats akin to human situation. Methodology/Principal Findings: Primary cultures of BM-MSCs (third passage) from Mutants, its lean littermate (Lean) and parental control (Control) were characterized for: proliferation markers, disease memory to mark obesity/T2D/HI/IR which included phased gene expression studies for adipogenic/pancreatic lineages, inflammatory markers and differentiation ability to form mature adipocytes/Insulin-like cellular aggregates (ILCAs). The data showed that BM-MSCs from Mutant demonstrated a state of disease memory, depicted by an upregulated expression of inflammatory markers (IL-6, TNFα); increased stem cell recruitment (Oct-4, Sox-2) and proliferation rates (CD90+/CD29+, PDA, 'S' phase of cell cycle by FACS and BrdU incorporation); accelerated preadipocyte induction (Dact-1, PPARγ2) with a quantitative increase in mature adipocyte formation (Leptin); ILCAs, which were non-responsive to high glucose did confer the Obese/T2D memory in Mutants. Further, these observations were in compliance with the anthropometric data. Conclusions: Given the ease of accessibility and availability of MSCs, the present study form the basis to report for the first time, application of BM-MSCs as a feasible in vitro model system to portray the disease memory of pre-clinical/T2D with IR - a major metabolic disorder of global concern. © 2012 Madhira et al.

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