scholarly journals Extrinsic Factors Involved in the Differentiation of Stem Cells into Insulin-Producing Cells: An Overview

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Rebecca S. Y. Wong
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Human Subjects ◽  
Contributing Factors ◽  
Extrinsic Factors ◽  
Oral Hypoglycaemic Agents ◽  
Insulin Producing Cells ◽  
Treatment Of Diabetes

Diabetes mellitus is a chronic disease with many debilitating complications. Treatment of diabetes mellitus mainly revolves around conventional oral hypoglycaemic agents and insulin replacement therapy. Recently, scientists have turned their attention to the generation of insulin-producing cells (IPCs) from stem cells of various sources. To date, many types of stem cells of human and animal origins have been successfully turned into IPCsin vitroand have been shown to exert glucose-lowering effectin vivo. However, scientists are still faced with the challenge of producing a sufficient number of IPCs that can in turn produce sufficient insulin for clinical use. A careful choice of stem cells, methods, and extrinsic factors for induction may all be contributing factors to successful production of functional beta-islet like IPCs. It is also important that the mechanism of differentiation and mechanism by which IPCs correct hyperglycaemia are carefully studied before they are used in human subjects.

Differentiation of mesenchymal stem cells from humans and animals into insulin-producing cells: An overview in vitro induction forms

2020 ◽  
Vol 16 ◽  
Author(s):  
Bruna O. S. Câmara ◽  
Bruno M. Bertassoli ◽  
Natália M. Ocarino ◽  
Rogéria Serakides
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Medium ◽  
Adipogenic Differentiation ◽  
Medium Composition ◽  
Cell Therapies ◽  
Insulin Producing Cells ◽  
Msc Differentiation

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.

scholarly journals Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Insulin-Producing Cells: Evidence for Further Maturation In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Mahmoud M. Gabr ◽  
Mahmoud M. Zakaria ◽  
Ayman F. Refaie ◽  
Sherry M. Khater ◽  
Sylvia A. Ashamallah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Trichostatin A ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Insulin Producing Cells ◽  
Parallel Increase

The aim of this study was to provide evidence for further in vivo maturation of insulin-producing cells (IPCs) derived from human bone marrow-derived mesenchymal stem cells (HBM-MSCs). HBM-MSCs were obtained from three insulin-dependent type 2 diabetic volunteers. Following expansion, cells were differentiated according to a trichostatin-A/GLP protocol. One million cells were transplanted under the renal capsule of 29 diabetic nude mice. Blood glucose, serum human insulin and c-peptide levels, and glucose tolerance curves were determined. Mice were euthanized 1, 2, 4, or 12 weeks after transplantation. IPC-bearing kidneys were immunolabeled, number of IPCs was counted, and expression of relevant genes was determined. At the end of in vitro differentiation, all pancreatic endocrine genes were expressed, albeit at very low values. The percentage of IPCs among transplanted cells was small (≤3%). Diabetic animals became euglycemic8±3days after transplantation. Thereafter, the percentage of IPCs reached a mean of ~18% at 4 weeks. Relative gene expression of insulin, glucagon, and somatostatin showed a parallel increase. The ability of the transplanted cells to induce euglycemia was due to their further maturation in the favorable in vivo microenvironment. Elucidation of the exact mechanism(s) involved requires further investigation.

scholarly journals Differentiation of Multipotent Stem Cells to Insulin-Producing Cells for Treatment of Diabetes Mellitus: Bone Marrow- and Adipose Tissue-Derived Cells Comparison

2021 ◽  
Author(s):  
Zahra Eydian ◽  
Alaleh Mohammad Ghasemi ◽  
Samira Ansari ◽  
Ali Naghi Kamali ◽  
Maryam Khosravi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Islet Cells ◽  
Human Adipose Tissue ◽  
Multipotent Stem Cells ◽  
C Peptide ◽  
Treatment Of Diabetes

Abstract Background: Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together.Methods and Results: MSCs were pre-induced with nicotinamide, mercaptoethanol, B-27 and b-FGF in L-DMEM for 2 days and re-induced again in supplemented H-DMEM for another 3 days. Expression of five genes in differentiated beta cells was evaluated by Real-time PCR and western blotting and the potency of insulin release in response to glucose stimulation was evaluated by insulin and C-peptide ELISA kit.Quantitative RT-PCR results showed up-regulation of four genes in differentiated beta-islet cells (Insulin, Ngn-3, Pax-4 and Pdx-1) compared with the control. Western blot analysis showed that MSCs cells mainly produced proinsulin and insulin after differentiation but nestin was more expressed in pre-differentiated stem cells. Glucose and insulin secretion assay showed that insulin levels and C-peptide secretion were significantly increased in response to 10 mM glucose.Conclusions: Our study showed that both adipose and bone marrow stem cells could differentiate into functional beta-islet cells but it seems that adipose stem cells could be a better choice for treatment of diabetes mellitus according to their more safety and potency.

scholarly journals Evidence of the hypoglycemic capacity of some natural products for the alternative treatment of diabetes mellitus type 2

2020 ◽  
Vol 8 (16) ◽  
pp. 56-64
Author(s):  
Karla Guadalupe Perez-Avila ◽  
Cruz Vargas-De-León ◽  
José Antonio Morales-González ◽  
Eduardo Madrigal-Santillán
Keyword(s):  
Diabetes Mellitus ◽  
Natural Products ◽  
Alternative Treatment ◽  
The Body ◽  
In Vitro Assays ◽  
Glucose Levels ◽  
Natural Treatment ◽  
Treatment Of Diabetes

Diabetes mellitus is a disease that is characterized by the chronic presence of blood glucose levels caused by a defect in the secretion of insulin or in the action of this hormone in the body which must be treated integrally with a multidisciplinary approach. The natural treatment of this disease is a common practice around the world, especially in Latin America, there are several clinical studies, in vivo or in vitro assays that focus on assessing the hypoglycemic capacity of various natural products used empirically by the population for years for the phytotherapeutic treatment of the disease as well as the chemicals related to the mechanism of action that produces the hypoglycaemic effect. In the present article, a brief review of the evidence of the hypoglycemic capacity of some natural products for the alternative treatment of diabetes mellitus 2

scholarly journals The Effect of Momordica charantia in the Treatment of Diabetes Mellitus: A Review

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Zhuo Liu ◽  
Jing Gong ◽  
Wenya Huang ◽  
Fuer Lu ◽  
Hui Dong
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Trials ◽  
Theoretical Basis ◽  
Momordica Charantia ◽  
In Vivo Experiments ◽  
New Ideas ◽  
Treatment Of Diabetes ◽  
The Common

In recent years, many studies of Momordica charantia (MC) in the treatment of diabetes mellitus (DM) and its complications have been reported. This article reviewed the effect and mechanism of MC against diabetes, including the results from in vitro and in vivo experiments and clinical trials. The common side effects of MC were also summarized. We hope that it might open up new ideas for further mechanism exploration and clinical application as well as provide a scientific theoretical basis for the development of drugs or foods derived from MC.

Pancreatic stem cells – new therapeutic option for the treatment of diabetes mellitus type 1

2002 ◽  
Vol 59 (11) ◽  
pp. 599-602
Author(s):  
Zulewski
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Ex Vivo ◽  
Therapeutic Option ◽  
Diabetes Mellitus Type 1 ◽  
Diabetes Mellitus Typ 1 ◽  
Pancreatic Stem Cells ◽  
Treatment Of Diabetes

Die Entdeckung von multipotentiellen Stammzellen in embryonalen und adulten Langerhans’schen Inseln des Pankreas lässt Hoffnungen keimen auf eine künftige Stammzell basierte Therapie des Diabetes mellitus Typ 1. Diese Stammzellen sind charakterisiert durch die Expression des Neurofilamentes Nestin, einem Marker für Stammzellen des Zentralen Nervensystems. Nestin positive Zellen aus humanen pankreatischen Inseln können ex vivo isoliert und expandiert werden. Sie bergen das Potenzial sich in vitro sowohl in Zellen mit pankreatisch-endokrinem als auch exokrinem Phänotyp zu differenzieren mit der Expression von Insulin und Glukagon sowie exokrinen Markern wie dem Zytokeratin19 und der Amylase. Zusätzlich haben diese pankreatischen Stammzellen die Fähigkeit in Kultur Proteine zu exprimieren, die einem hepatischen Phänotyp entsprechen. Die Differenzierung Nestin-positiver Stammzellen in Insulin exprimierende Zellen wird entscheidend gefördert durch das insulinotrope Hormon GLP-1.

scholarly journals Enhanced Production of Mesencephalic Dopaminergic Neurons from Lineage-Restricted Human Undifferentiated Stem Cells

2021 ◽  
Author(s):  
Muyesier Maimaitili ◽  
Muwan Chen ◽  
Fabia Febbraro ◽  
Noëmie Mermet-Joret ◽  
Johanne Lauritsen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Motor Behavior ◽  
Cell Types ◽  
Extrinsic Factors ◽  
Enhanced Production ◽  
Novel Strategy ◽  
6 Hydroxydopamine

The differentiation of human pluripotent stem cells (hPSCs) into mesencephalic dopaminergic (mesDA) neurons requires a precise combination of extrinsic factors that recapitulates the in vivo environment and timing. Current methods are capable of generating authentic mesDA neurons after long-term culture in vitro; however, when mesDA progenitors are transplanted in vivo, the resulting mesDA neurons are only minor components of the graft. This low yield hampers the broad use of these cells in the clinic. In this study, we genetically modified pluripotent stem cells to generate a novel type of stem cells called lineage-restricted undifferentiated stem cells (LR-USCs), which robustly generate mesDA neurons. LR-USCs are prevented from differentiating into a broad range of nondopaminergic cell types by knocking out genes that are critical for the specification of cells of alternate lineages. Specifically, we target transcription factors involved in the production of spinal cord and posterior hindbrain cell types. When LR-USCs are differentiated under caudalizing condition, which normally give rise to hindbrain cell types, a large proportion adopt a midbrain identity and develop into authentic mesDA neurons. We show that the mesDA neurons are electrophysiologically active, and due to their higher purity, are capable of restoring motor behavior eight weeks after transplantation into 6-hydroxydopamine (6-OHDA)-lesioned rats. This novel strategy improves the reliability and scalability of mesDA neuron generation for clinical use.

scholarly journals Hybrid drug combination: A new treatment strategy for type 2 diabetes- A review

2020 ◽  
Vol 11 (2) ◽  
pp. 2008-2017
Author(s):  
Shraddha Sharma ◽  
Vengal Rao P ◽  
Seema Mehdi ◽  
Manjula S N ◽  
Aalap Das
Keyword(s):  
Diabetes Mellitus ◽  
Side Effects ◽  
Synthetic Drugs ◽  
Treatment Of Diabetes ◽  
New Treatment ◽  
Bioactive Agents ◽  
Oral Hypoglycemic Drugs

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia arising from deregulation in insulin secretion, insulin action, or both. The current synthetic drugs have dose-dependent side effects which confined their uses. The phytochemicals are the natural compounds that have better therapeutic efficacy and interacts synergistically with oral hypoglycemic drugs. The addition of phytochemicals with OHDs may reduce the dose of synthetic drugs as well as their side effects and toxicity. A detailed outline about such combinations like Ferulic acid & THZ/Metformin, Ellagic acid & Pioglitazone (THZ), Chlorogenic acid & THZ/Metformin, Caffeic acid & THZ/Metformin, eugenol acid & THZ/Metformin, cinnamic acid & THZ/Metformin, p- coumaric acid & THZ/Metformin, Arecoline &Vanillic acid with the THZ/ Metformin have been illustrated. This review has also discussed the synergy and mechanism of phytochemical with the OHDs to combat hyperglycemia and other risk associated with it. A comprehensive review was conducted to pile up the information about polyphenols & synthetic drug combinations used for the treatment of diabetes mellitus, which has been carried out in-vitro or in-vivo and may contribute to identifying novel strategies in the treatment of T2D condition. This review shows the importance of the responsible bioactive agents present in medicinal plants in the drive to demonstrate their antidiabetic effects.

scholarly journals Preventive and Protective Properties ofZingiber officinale(Ginger) in Diabetes Mellitus, Diabetic Complications, and Associated Lipid and Other Metabolic Disorders: A Brief Review

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Yiming Li ◽  
Van H. Tran ◽  
Colin C. Duke ◽  
Basil D. Roufogalis
Keyword(s):  
Diabetes Mellitus ◽  
Zingiber Officinale ◽  
Neural System ◽  
Protective Effects ◽  
Protective Properties ◽  
Safety Issues ◽  
Carbohydrate And Lipid Metabolism ◽  
Treatment Of Diabetes

Zingiber officinale(ginger) has been used as herbal medicine to treat various ailments worldwide since antiquity. Recent evidence revealed the potential of ginger for treatment of diabetes mellitus. Data fromin vitro, in vivo, and clinical trials has demonstrated the antihyperglycaemic effect of ginger. The mechanisms underlying these actions are associated with insulin release and action, and improved carbohydrate and lipid metabolism. The most active ingredients in ginger are the pungent principles, gingerols, and shogaol. Ginger has shown prominent protective effects on diabetic liver, kidney, eye, and neural system complications. The pharmacokinetics, bioavailability, and the safety issues of ginger are also discussed in this update.

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