Mesenchymal Stem Cells as a Treatment for Peripheral Arterial Disease: Current Status and Potential Impact of Type II Diabetes on Their Therapeutic Efficacy

Yan, Jinglian; Tie, Guodong; Xu, Ting; Cecchini, Katharine; Messina, Louis M.

doi:10.1007/s12015-013-9433-8

Cited by 56 publications

(46 citation statements)

References 86 publications

(86 reference statements)

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“…124 Preclinical findings showed that bone marrow–derived mesenchymal stem cells (BM-MSCs) injected into ischemic hind limbs of rats led to greater perfusion and capillary density increase than BM-MNC administration. A randomized controlled trial comparing BM-MSCs to BM-MNCs was conducted on 41 CLI patients with diabetes mellitus and demonstrated significantly improved pain-free walking time in both groups at 6 months.…”

Section: Trials Of Cell-based Therapiesmentioning

confidence: 99%

Modulating the Vascular Response to Limb Ischemia

Cooke

Losordo

2015

Circulation Research

189

151

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The age-adjusted prevalence of peripheral arterial disease in the US population has been estimated to approach 12%. The clinical consequences of occlusive peripheral arterial disease include pain on walking (claudication), pain at rest, and loss of tissue integrity in the distal limbs; the latter may ultimately lead to amputation of a portion of the lower extremity. Surgical bypass techniques and percutaneous catheter-based interventions may successfully reperfuse the limbs of certain patients with peripheral arterial disease. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and healing of ischemic ulcers. No effective medical therapy is available for the treatment of such patients, for many of whom amputation represents the only hope for alleviation of symptoms. The ultimate failure of medical treatment and procedural revascularization in significant numbers of patients has led to attempts to develop alternative therapies for ischemic disease. These strategies include administration of angiogenic cytokines, either as recombinant protein or as gene therapy, and more recently, to investigations of stem/progenitor cell therapy. The purpose of this review is to provide an outline of the preclinical basis for angiogenic and stem cell therapies, review the clinical research that has been done, summarize the lessons learned, identify gaps in knowledge, and suggest a course toward successfully addressing an unmet medical need in a large and growing patient population.

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Section: Trials Of Cell-based Therapiesmentioning

confidence: 99%

Modulating the Vascular Response to Limb Ischemia

Cooke

Losordo

2015

Circulation Research

189

151

View full text Add to dashboard Cite

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“…These include bone marrow and peripheral blood mononuclear cells [11][12][13][14][15][16][17], mesenchymal stem cells (MSCs) [18][19][20][21][22], cell lines selected based on the presence of specific markers [15,[23][24][25], adipose tissue-derived cells [26][27][28][29], and induced pluripotent stem cells-derived cells [30,31]. Each of these cell types has shown promise for the treatment of CLI in mechanistic and preclinical studies.…”

Section: Introductionsmentioning

confidence: 99%

Regulating myogenic differentiation of mesenchymal stem cells using thermosensitive hydrogels

et al. 2015

Acta Biomaterialia

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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).…”

mentioning

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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Mesenchymal Stem Cells as a Treatment for Peripheral Arterial Disease: Current Status and Potential Impact of Type II Diabetes on Their Therapeutic Efficacy

Cited by 56 publications

References 86 publications

Modulating the Vascular Response to Limb Ischemia

Modulating the Vascular Response to Limb Ischemia

Regulating myogenic differentiation of mesenchymal stem cells using thermosensitive hydrogels

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

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