Can Functionally Mature Islet ß-Cells be Derived from Pluripotent Stem Cells? A Step Towards Ready-To-Use ß-Cells in Type 1 Diabetes.

Pluripotent Stem Cells [PSCs] are emerging as an excellent cellular source for the treatment of many degenerative diseases such as diabetes, ischemic heart failure, Alzheimer's disease, etc. PSCderived pancreatic islet ß-cells appear to be a promising therapy for type 1 diabetic patients with impaired ß-cell function. Several protocols have been developed to derive ß-cells from PSCs. However, these protocols produce ß-like cells that show low glucose stimulated insulin secretion (GSIS) function and mirror GSIS profile of functionally immature neonatal ß-cells. Several studies have documented a positive correlation between the sirtuins (a family of ageing-related proteins) and the GSIS function of adult ß-cells. We are of the view that the GSIS function of PSC-derived ß-like cells could be enhanced by improving the function of sirtuins in them. Studying the sirtuin expression and activation pattern during the ß-cell development and inclusion of the sirtuin activators and inhibitor cocktail (specific to a developmental stage) in the present protocols may help us derive functionally mature, ready-to-use ß- cells in-vitro making them suitable for transplantation in type 1 diabetes.

Wound with Diabetes: Present Scenario and Future.

Diabetes is a chronic metabolic disorder of the endocrine system characterized by an increase in blood glucose level. Several factors, such as pancreatic damage, oxidative stress, infection, genetic factor, obesity, liver dysfunction, play a vital role in the pathogenesis of diabetes, which further leads to serious diabetic complications. The diabetic wound is one such complication where the wound formation occurs, especially due to pressure and its healing process is disrupted due to factors, such as hyperglycemia, neuropathy, nephropathy, peripheral vascular disease, reduction of blood flow, atherosclerosis, impaired fibroblast. The process of wound healing is delayed due to different abnormalities like alteration in nitric oxide level, increase in aldose reductase, sorbitol, and fructose. Therefore, diabetic wound requires more time to heal as compared to the normal wound. Healing time is delayed in diabetic wound due to many factors, such as stress, decreased oxygenation supply, infection, decreased blood flow, impaired proliferation and migration rate, impaired growth factor production, impaired keratinocytes proliferation and migration, and altered vascular endothelial mediators. The current treatment for diabetic wounds includes wound patches, oxygenation therapy, hydrogel patches, gene therapy, laser therapy, and stem cell therapy. Medications with phytoconstituents are also one way to manage the diabetic wound, but it is not more effective for quick healing. The objective of this review is to understand the potential of various management options which are available for diabetic wound, with a special focus on biological cells.

Placental mesenchymal stromal cells as an alternative tool for therapeutic angiogenesis.

Dysregulation of angiogenesis is a phenomenon observed in several disorders such as diabetic foot, critical limb ischemia and myocardial infarction. Mesenchymal stromal cells (MSCs) possess angiogenic potential and have recently emerged as a powerful tool for cell therapy to promote angiogenesis. Although bone marrow-derived MSCs are the primary cell of choice, obtaining them has become a challenge. The placenta has become a popular alternative as it is a highly vascular organ, easily available and ethically more favorable with a rich supply of MSCs. Comparatively, placenta-derived MSCs (PMSCs) are clinically promising due to their proliferative, migratory, clonogenic and immunomodulatory properties. PMSCs release a plethora of cytokines and chemokines key to angiogenic signaling and facilitate the possibility of delivering PMSC-derived exosomes as a targeted therapy to promote angiogenesis. However, there still remains the challenge of heterogeneity in the isolated populations, questions on the maternal or fetal origin of these cells and the diversity in previously reported isolation and culture conditions. Nonetheless, the growing rate of clinical trials using PMSCs clearly indicates a shift in favor of PMSCs. The overall aim of the review is to highlight the importance of this rather poorly understood cell type and emphasize the need for further investigations into their angiogenic potential as an alternative source for therapeutic angiogenesis.

Human adipose tissue mesenchymal stem cells as a novel treatment modality for correcting obesity induced metabolic dysregulation.

OBJECTIVE: Obesity induced metabolic dysregulation results in cluster of chronic conditions mainly hyperglycemia, hyperinsulinemia, dyslipidemia, diabetes, cardiovascular complications and insulin resistance. To investigate the effect of i.m. injection of human adipose tissue derived mesenchymal stem cells and its secretome in correcting obesity induced metabolic dysregulation in high fat diet fed obese model of mice and understand its mechanism of action. SUBJECTS: We injected human adipose tissue derived mesenchymal stem cells (ADMSCs) suspension (CS), conditioned medium (CM) and the cell lysate (CL) intramuscularly in high fat diet (HFD)-induced C57BL/6 mice. Metformin was used as a positive control. ADMSCs were traced in vivo for its bio distribution after injection at different time points. RESULTS: ADMSCs-treated mice exhibited remarkable decrease in insulin resistance as quantified by HOMA-IR and triglyceride glucose index with concomitant decrease in oxidized LDL and IL6 as compared with the untreated control. CS injection showed improvement in glucose tolerance and reduction in fatty infiltration in the liver, macrophage infiltration in adipose and hypertrophy of the islets resulting from HFD. Upregulation of miRNA-206, MyoD and increase in protein content of the skeletal muscle in CS-treated mice indicates plausible mechanism of action of ADMSCs treatment in ameliorating IR in HFD mice. CONCLUSION: Of all the three treatments, CS was found to be the best. ADMSCs were found to have migrated to different organs in order to bring about the correction in dysregulated metabolism induced by obesity. Our results open up a novel treatment modality for possible therapeutic usage in human subjects by employing autologous or allogeneic ADMSCs for the better management of obesity induced metabolic dysregulation.

Long term explant culture for harvesting homogeneous population of human dental pulp stem cells.

Dental pulp stem cells have emerged as a preferred source of mesenchymal stem cells, because of its easy availability and high stem cell content. Dental pulp is a specific fibrous tissue that contains heterogeneous populations of odontoblasts, fibroblasts, pericytes, progenitors, stem cells, leukocytes and neuronal cells. In this study, we propose sustained explant culture as a simple, economical and efficient process to isolate dental pulp stem cells from human Dental pulp Tissue. Historically explant cultures were used to get fibroblast cells from embryonic chick heart using plasma clot cultures. The subculture was performed by lifting mother explant (original explant) and grafting it in a new plasma clot. We modified this age old technique to suit the modern times. Here we demonstrate for the first time that the mother explant (E0) of human dental pulp tissue could be sub-cultured consecutively seven times (E7) without displacement. This technique is highly reproducible and permits growth and proliferation of dental pulp stem cells yielding an enriched homogeneous mesenchymal stem cells population in the first passage itself as revealed by surface marker expression. These dental pulp stem cells exhibit differentiation into adipogenic, chondrogenic and osteogenic lineage revealing their mesenchymal stem cell nature. We propose that dental pulp stem cells isolated by sustained explant culture are phenotypically and functionally comparable to those obtained by enzymatic method. It is a simple, inexpensive and gentle method, which may be preferred over the conventional techniques for obtaining stem cells from other tissue sources as well especially in cases of limited starting material.

Establishment of an in ovo chick embryo yolk sac membrane (YSM) assay for pilot screening of potential angiogenic and anti-angiogenic agents.

Angiogenesis, the process of new blood vessel formation from pre-existing vessels, is essential for growth and development. Development of drugs that can accelerate or decelerate angiogenesis in the context of various diseases requires appropriate preclinical screening. As angiogenesis involves complex cellular and molecular processes, in vivo studies are superior to in vitro investigations. Conventional in vitro, in vivo, and ex ovo models of angiogenesis are time consuming and tedious, and require sophisticated infrastructure for embryo culture. In the present study, we established an in ovo chick embryo yolk sac membrane (YSM) assay for angiogenesis and tested the angiogenic potential of arginine, conditioned medium (CM) from human adipose tissue and placenta-derived mesenchymal stem cells (ADMSCs-CM and PDMSCs-CM), avastin and vitamin C. The obtained results were confirmed with the routinely employed chick embryo Chorioallantoic Membrane (CAM) assay. Both assays revealed the pro-angiogenic nature of arginine, ADMSCs-CM, and PDMSCs-CM, and the anti-angiogenic effect of avastin and vitamin C. This novel in ovo YSM model is simple, reproducible, and highly economic in terms of the time frame and cost incurred. The proposed model is thus a suitable substitute to the CAM model for pilot screening of potential angiogenic and anti-angiogenic agents.

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.

Human Umbilical Cord-Derived Stem Cells: Isolation, Characterization, Differentiation, and Application in Treating Diabetes.

Stem cell therapy is one of the most promising and effective approaches for treating diabetes, due to stem cell nonimmunogenic and nonimmunosupressive properties. Mesenchymal stem cells (MSCs) derived from human umbilical cord have been widely used in cell-based therapies for clinical applications. Among their various properties, immunomodulatory and proregenerative capacities broaden their scope for treating diabetes. Owing to various problems that are involved in treating diabetes, our review focuses on modulating umbilical cord-derived MSCs (UCMSCs) without any genetic manipulation. Umbilical cord tissue contains a rich source of MSCs with intact stemness. UCMSCs have profound effects on the remodeling process, maintaining similar morphology to various organs and escalating vascularization. Because of their neonatal origin, MSCs have enormous immune properties that lead to greater therapeutic benefits, including enhanced insulin sensitivity in type 2 diabetic (T2D) animal models and treatment of complications such as diabetic ulcers and compromised wound healing. MSCs ameliorate hyperglycemia by reducing inflammation due to their anti-inflammatory nature. Furthermore, their differentiation potential enables use in T1D treatment, wherein MSCs alone or insulin-producing cells that are derived from these MSCs, when transplanted in streptozotocin, induce animals to experience reversal of hyperglycemia. In this review, we discuss methods of UCMSC isolation, characterization, differentiation potential, and various applications in diabetes treatment.

Treatment with adipose derived mesenchymal stem cells and their conditioned media reverse carrageenan induced paw oedema in db/db mice.

Mesenchymal stem cells are known for anti inflammatory and immunomodulatory activities. The aim of our study was to evaluate the effect of human adipose derived mesenchymal stem cells (hADMSCs) and its conditioned media (CM) on carrageenan induced acute inflammation in db/db mice. We injected 5×105 ADMSCs or the CM in the inflamed paw. We assessed the paw volume, serum IL6 levels and histopathology of the paw to reveal the anti inflammatory effect. We observed a single injection of hADMSCs or CM could reverse the inflammation within 24h as evidenced by reduction in paw volume, IL6 levels and histological examination. Our result equivocally demonstrates the role of CM in normalising the inflammation better than hADMSCs. This study will pave way for an alternative to anti inflammatory drugs.

Regenerative therapy for hippocampal degenerative diseases: lessons from preclinical studies.

Increase in life expectancy has put neurodegenerative diseases on the rise. Amongst these, degenerative diseases involving hippocampus like Alzheimer's disease (AD) and temporal lobe epilepsy (TLE) are ranked higher as it is vulnerable to excitotoxicity induced neuronal dysfunction and death resulting in cognitive impairment. Modern medicines have not succeeded in halting the progression of these diseases rendering them incurable and often fatal. Under such scenario, regenerative studies employing stem cells or their by-products in animal models of AD and TLE have yielded encourageing results. This review focuses on the distinct cell types, such as hippocampal cell lines, neural precursor cells, embryonic stem cells derived neural precursor cells, induced pluripotent stem cells, induced neurons and mesenchymal stem cells, which can be employed to rescue hippocampal functions in neurodegenerative diseases like AD and TLE. Besides, the divergent mechanisms through which cell based therapy confer neuroprotection, current impediments and possible improvements in stem cell transplantation strategies are discussed. Authors are aware of the voluminous literature available on this issue and have made a sincere attempt to put forth the current status of research in the field of cell based therapy concurrently discussing the promise it holds for combating neurodegenerative diseases like AD and TLE in the near future. Copyright © 2015 John Wiley & Sons, Ltd.

Conditioned Media From Adipose Tissue Derived Mesenchymal Stem Cells Reverse Insulin Resistance in Cellular Models.

The link between insulin resistance (IR) and type 2 diabetes has been recognized for a long time. Type 2 diabetes is often associated with basal hyperinsulinemia, reduced sensitivity to insulin, and disturbances in insulin release. There are evidences showing the reversal of IR by mesenchymal stem cells. However, the effect of conditioned media from adipose derived mesenchymal stem cells (ADSCs-CM) in reversal of IR has not been established. We established an insulin resistant model of 3T3L1 and C2C12 cells and treated with ADSCs-CM. 2-NBDG (2-[N-[7-Nitrobenz-2-oxa-1,3-diazol-4-yl]Amino]-2-Deoxyglucose) uptake was performed to assess improvement in glucose uptake. Genes involved in glucose transport and in inflammation were also analysed. Western blot for glucose transporter-4 and Akt was performed to evaluate translocation of Glut4 and insulin signaling respectively. We found that the ADSCs-CM treated cells restored insulin, stimulated glucose uptake as compared to the untreated control indicating the insulin sensitizing effect of the CM. The treated cells also showed inhibition adipogenesis in 3T3L1 cells and significant reduction of intramuscular triglyceride accumulation in C2C12 cells. Gene expressions studies revealed the drastic upregulation of GLUT4 gene and significant reduction in IL6 and PAI1 gene in both 3T3L1 and C2C12 cells, indicating possible mechanism of glucose uptake with concomitant decrease in inflammation. Enhancement of GLUT4 and phospho Akt protein expression seems to be responsible for the increment in glucose uptake and enhanced insulin signaling, respectively. Our study revealed for the first time that ADSCs-CM acts as an alternative insulin sensitizer providing stem cell solution to IR. J. Cell. Biochem. 118: 2037-2043,2017. © 2016 Wiley Periodicals, Inc.

Metformin preconditioned adipose derived mesenchymal stem cells is a better option for the reversal of diabetes upon transplantation.

Metformin is used worldwide as an insulin sensitizer. Adipose derived mesenchymal stem cells have shown promising results in the reducing hyperglycemia. We examined whether preconditioning of adipose derived mesenchymal stem cells (ASCs) with metformin could have a better therapeutic value for the reversal of type 2 diabetes. We compared the effect of metformin, ASCs and metformin preconditioned ASCs (MetASCs) in high fat diet induced C57BL/6 mice by injecting the cells intramuscularly only once where as metformin was given at a concentration of 300mg per kg body weight orally daily. Fasting glucose was measured every week for 4 weeks. At the end of the study insulin, triglycerides, IL6 and oxidised LDL were evaluated from the serum. Gene expression studies were performed for muscle (GLUT4) and liver tissues (IL6 and PAI1).There was a remarkable decrease in hyperglycemia within two weeks of injection by MetASCs as compared to metformin and ASCs alone. A significant decrement of hyperinsulinemia, triglyceridemia, serum IL6 and oxidised LDL were observed at the end of the study. Gene expression studies for muscle tissue revealed the drastic upregulation of GLUT4 gene levels in the MetASCs group indicating enhanced glucose uptake in muscle. Liver tissue analysed for the genes involved in inflammation viz. IL6 and PAI1 showed significant downregulation in the MetASCs group as compared to the other groups. This is a first report demonstrating the synergistic effect of metformin preconditioning of ASCs leading to reversal of hyperglycemia, hyperinsulinemia and triglyceridemia.

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.

Infusion of human embryonic kidney cell line conditioned medium reverses kainic acid induced hippocampal damage in mice.

BACKGROUND AIMS: Hippocampal neurodegeneration is one of the hallmarks in neurological and neurodegenerative diseases such as temporal lobe epilepsy and Alzheimer disease. Human embryonic kidney (HEK) cells are a mixed population of cells, including neurons, and their conditioned medium is enriched with erythropoietin (EPO). Because EPO is a known neuroprotectant, we hypothesized that infusion of HEK cells or HEK-conditioned medium (HEK-CM) may provide neuroprotection against kainic acid (KA)-induced hippocampal damage in mice. METHODS: Adult CF1 mice were treated with KA to induce hippocampal damage. On 3rd and 5th days after KA treatment, HEK cells or HEK-CM was infused intravenously through the tail vein. On the 7th and 8th days after KA treatment, all groups of mice were subjected to cognitive and depression assessment by use of a novel object recognition test and a forced swim test, respectively. Subsequent to this assessment, mice were killed and the brain samples were used to assess the histopathology and messenger RNA expression for EPO and B-cell lymphoma-2 (Bcl-2). RESULTS: We found that infusion of HEK cells/HEK-CM improves cognitive function and alleviates symptoms of depression. Histological assessment demonstrates complete neuroprotection against KA-mediated excitotoxicity, and the hippocampal cytoarchitecture of HEK cells/HEK-CM treated mice was comparable to normal control mice. HEK cells/HEK-CM treatment could provide neuroprotection by upregulating the endogenous EPO and Bcl-2 in KA-treated mice. CONCLUSIONS: Our present data demonstrate for the first time that infusion of HEK cells/HEK-CM can prevent excitotoxic hippocampal damage and alleviate consequent behavioral abnormalities.

Ectopically tethered CP190 induces large-scale chromatin decondensation.

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.

Islet adaptation to obesity and insulin resistance in WNIN/GR-Ob rats.

WNIN/GR-Ob mutant rat is a novel animal model to study metabolic syndrome (obesity, insulin resistance, hyperinsulinemia, impaired glucose tolerance and cardiovascular diseases). We have investigated the islet characteristics of obese mutants at different age groups (1, 6 and 12 months) to assess the islet changes in response to early and chronic metabolic stress. Our data demonstrates altered islet cell morphology and function (hypertrophy, fibrotic lesions, vacuolation, decreased stimulation index, increased TNFα, ROS and TBARS levels) in mutants as compared to controls. Furthermore, network analysis (gene-gene interaction) studied in pancreas demonstrated increased inflammation as a key factor underlying obesity/metabolic syndrome in mutants. These observations pave way to explore this model to understand islet adaptation in response to metabolic syndrome.

Making surrogate ß-cells from mesenchymal stromal cells: perspectives and future endeavors.

Generation of surrogate ß-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 ß-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.

Diverse roles of metformin during peri-implantation development: revisiting novel molecular mechanisms underlying clinical implications.

Metformin is not only a widely used oral antidiabetic drug, which acts as an insulin sensitizer and suppressor of hepatic gluconeogenesis, but it also exhibits antitumor properties. Besides, it has been utilized in the treatment of polycystic ovary syndrome (PCOS) for infertile women with glucose intolerance and as a component of combination therapy to reduce early (first trimester) pregnancy loss or spontaneous abortion (SAB). Based on recent studies demonstrating its beneficial effects on mothers and the fetus, metformin is even recommended for later stages of pregnancy. Probing into the mechanism of action revealed that it can activate a stress modulatory pathway, none other than the AMP-activated protein kinase (AMPK) via LKB 1. It is well accepted that AMPK signaling plays a crucial role during implantation by combating stress in multiple ways. Stress factors commonly encountered during pregnancy are malnutrition, diabetes, and hypoxia, which may result in SABs or other complications. For instance, the elevated levels of insulin, which are a typical characteristic of hyperinsulinemic, obese, or PCOS patients, can impair the development of the blastocyst and the preimplantation embryo. Further, a severe hypoxic environment prompts early and untimely differentiation of the embryonic cells leading to abnormal growth and development. Therefore, the modulation of stress-related pathways could be pivotal in ameliorating such stress responses during implantation. Here we hypothesize a putative noncanonical pathway underpinning the role of metformin in high-risk pregnancies to counteract stress by recreating an in vitro replica of human implantation, engaging embryonic stem cells, trophoblast stem cells, and endometrial stromal cells in a three-dimensional scaffold.

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.