Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

El‐Badri, Nagwa; Ghoneim, Mohamed A.

doi:10.1155/2013/194858

Cited by 41 publications

(35 citation statements)

References 69 publications

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“…Despite corneal transplantation is the most successful solid organ transplantation, immune rejection is still the major cause of graft failure. Over the last decade, mesenchymal stem cell (MSC) therapy has been proposed and used as a possible treatment strategy for cardiovascular diseases, renal wound repair, diabetes, systemic lupus erythematosus, and solid organ transplantation [4][5][6][7] . MSCs are a promising stem cell population because of their self-renewal, pluripotential capability, low immunogenicity properties, and notable immunomodulatory and anti-inflammatory activities [8] .…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

Li¹

2014

WJSC

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Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain problematic. Mesenchymal stem cells (MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro . These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In addition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoimmune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

Li¹

2014

WJSC

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“…In animal experiments of MSC transplantation for treating hyperglycemia and diabetes-related complications, it is indicated that paracrine and anti-inflammatory effects of MSCs are the primary mechanisms of action (19)(20)(21)(22) rather than direct engraftment and differentiation into insulin-producing cells (23,24).…”

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confidence: 99%

Niche-Dependent Regulations of Metabolic Balance in High-Fat Diet–Induced Diabetic Mice by Mesenchymal Stromal Cells

Chang

et al. 2014

Diabetes

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Mesenchymal stromal cells (MSCs) have great potential to maintain glucose homeostasis and metabolic balance. Here, we demonstrate that in mice continuously fed with high-fat diet (HFD) that developed non-insulindependent diabetes, two episodes of systemic MSC transplantations effectively improve glucose tolerance and blood glucose homeostasis and reduce body weight through targeting pancreas and insulin-sensitive tissues and organs via site-specific mechanisms. MSCs support pancreatic islet growth by direct differentiation into insulin-producing cells and by mitigating the cytotoxicity of interleukin 1 (IL-1) and tumor necrosis factor-a (TNF-a) in the pancreas. Localization of MSCs in the liver and skeletal muscles in diabetic animals is also enhanced and therefore improves glucose tolerance, although long-term engraftment is not observed. MSCs prevent HFD-induced fatty liver development and restore glycogen storage in hepatocytes. Increased expression of IL-1 receptor antagonist and Glut4 in skeletal muscles after MSC transplantation results in better blood glucose homeostasis. Intriguingly, systemic MSC transplantation does not alter adipocyte number, but it decreases HFD-induced cell infiltration in adipose tissues and reduces serum levels of adipokines, including leptin and TNF-a. Taken together, systemic MSC transplantation ameliorates HFD-induced obesity and restores metabolic balance through multisystemic regulations that are niche dependent. Such findings have supported systemic transplantation of MSCs to correct metabolic imbalance.Impairment of glucose tolerance and insulin resistance initiates type 2 diabetes; however, exhaustion of the insulin supply due to b-cell apoptosis is the ultimate pathomechanism of both type 1 and 2 diabetes (1,2). The liver, adipose tissues, skeletal muscles, and vascular tissues are insulin-sensitive tissues responsible for blood glucose homeostasis (1,3). Inflammation adversely affects insulin sensitivity and worsens diabetic retinopathies, neuropathies, and vasculopathies (4-6). Proinflammatory cytokines produced by macrophages, such as tumor necrosis factor-a (TNF-a) and interleukin 1 (IL-1), create a vicious cycle of reduced insulin sensitivity (3,(7)(8)(9).To the present, more than 300 clinical trials of mesenchymal stem/stromal cell (MSC) transplantations have been conducted worldwide with a wide clinical application targeting more than 50 indications (www.clinicaltrials.gov). Systemic transplantation is the most favorable route for MSC delivery from a safety and systemic regulation point of view, and 56% of MSC clinical trials are allogenic transplantation (10). It is well accepted that the majority of MSCs are initially distributed in vital organs (11-16) and are also frequently found in tissues of mesenchymal origin (11,12) when systemically administered. Nevertheless, the long-term engraftment of MSCs is minimal, and the engraftment rate is not correlated with therapeutic response in human studies (17). The acutely diseased and damaged tissues show increased loca...

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“…Alpha-glucosidase inhibitors-This class of drugs (Acarbose, voglibose and miglitol) acts by slowing the carbohydrates absorption by inhibition of alpha-glucosidases, dropping the postprandial rise in blood glucose level [40,41].…”

Section: Few Of the Most Recent Classes Of The Anti-diabetic Drugs Armentioning

confidence: 99%

Untitled

2017

MOJDDT

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As the prevalence of type 2 diabetes (T2D) is rapidly increasing, and effective strategies to manage and prevent this disease are urgently required, as per WHO statistics undertaken in 2012, the number of people suffering from T2D in India is expected to shoot up from 40.9 million in 2007 to 69.9 million by the year 2025. Even though, the symptoms of T2D are seen in the later stages of life, the onset of the disease occurs quite early and is referred to as lifestyle disorder. Insulin resistance and β cell dysfunction are the main causative factors along with mutations in the genes regulating glucose homeostasis and β cell development. A vicious circle of the causes and effects of hyperglycemia interlinked together forms the whole picture of T2D. Our review discusses the molecular targets of the current oral therapeutic drugs, which cuts down hyperglycemia. This review aims to provide better insights to comprehension of the disease, recent advances in molecular and cellular therapies. A comprehensive analysis of these novel targets identified over the years and various therapeutic leads which successfully completed their clinical trials are presented in this review. Few of these lead molecules operate as GLP-1 agonist, SGLT2 inhibitors, and DPP-IV inhibitors and are termed as next generation anti-diabetic drugs.

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Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

Cited by 41 publications

References 69 publications

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

Niche-Dependent Regulations of Metabolic Balance in High-Fat Diet–Induced Diabetic Mice by Mesenchymal Stromal Cells

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