Treatment of Foot Disease in Patients with Type 2 Diabetes Mellitus using Human Umbilical Cord Blood Mesenchymal Stem Cells: Response and Correction of Immunological Anomalies

Li, Xiaoyan; Zheng, Zhaohui; Li, Xueyi; Guo, Jialong; Zhang, Yan; Li, Hui; Wang, Yangwei; Ren, Jun; Wu, Zhenbiao

doi:10.2174/13816128113199990326

Cited by 61 publications

(47 citation statements)

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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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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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“…The collagen synthesis of the healthy fibroblast group was 210 AE 34 ng/mL, which was also greater than that of the diabetic fibroblasts. dependent on the overall health status of the recipient [30]. On the basis of these biological advantages, a combination of hUCB-MSCs and sodium hyaluronate (CARTISTEM, Medipost Co Ltd) is intended for use as a single-dose cellular therapeutic agent for cartilage regeneration in human subjects with cartilage defects of the knee caused by aging, trauma or degenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Wound-healing potential of human umbilical cord blood–derived mesenchymal stromal cells in vitro—a pilot study

et al. 2015

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“…In many researches have been demonstrated that medicine regenerative strategies in patients were best than conventional therapies, without collateral effects have been seen [30,[60][61][62][63][64][65]. This becomes to RM an important element of support to the treatment in the case of cutaneous wounds with small possibilities of healing [66,67].…”

Section: Introductionmentioning

confidence: 99%

Transcendence of Medicine Regenerative Strategies in the Treatment for Diabetic Foot Ulcers

Díaz-García¹,

Benítez-Arvizu²

2016

J Cancer Diagn

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The Diabetes Mellitus type 2 and one of its complications, the diabetic foot ulcer (DFU), are a great problem of public health that affects millions of people around the world. Due to its complexity, DFUs treatment and handling are expensive and complex. In addition, amputations of lower limbs and death are relatively frequent because conventional treatment cannot avoid them. In other hand, the use of growth factors, 3D scaffolds and mesenchymal stem cells, called regenerative medicine (RM), have created new perspectives about the treatment of this kind of injuries. The RM has demonstrated favorable clinical outcomes not only in the case of DFUs, so that, this new medicine area promises to become an important tool that supports or substitutes to conventional treatment in cases of tissue or organic damage caused by the different chronic and traumatic diseases.

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Treatment of Foot Disease in Patients with Type 2 Diabetes Mellitus using Human Umbilical Cord Blood Mesenchymal Stem Cells: Response and Correction of Immunological Anomalies

Cited by 61 publications

References 0 publications

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

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

Wound-healing potential of human umbilical cord blood–derived mesenchymal stromal cells in vitro—a pilot study

Transcendence of Medicine Regenerative Strategies in the Treatment for Diabetic Foot Ulcers

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