Autologous peripheral blood mononuclear cell implantation for patients with peripheral arterial disease improves limb ischemia
ABSTRACT Implantation of bone marrow mononuclear cells, including endothelial progenitor cells, into ischemic limbs has been shown to improve collateral vessel formation. In the present study the safety and feasibility of autologous peripheral blood mononuclear cells (PBMNCs) implantation after granulocyte-colony stimulating factor (G-CSF)-induced mobilization was investigated in patients with severe peripheral arterial disease.
Six cases were enrolled: 5 of thromboangitis obliterans and 1 of arteriosclerosis obliterans. Following administration of G-CSF (10 microg . kg(-1) . day(-1)), PBMNCs were harvested and injected intramuscularly (5 legs and 1 arm) for 2 days for the patients with ischemia of the legs. No serious adverse events related to G-CSF administration, harvest or implantation were observed during this study period. Improvement in the ankle - brachial pressure index (ABI: >0.1) was seen in 4 patients at 4 weeks and ischemic ulcers improved in 3 of 3 patients. The mean maximum walking distance significantly increased from 203 m to 559 m (p=0.031) at 4 weeks and was sustained for 24 weeks. Significant improvement was seen in physiological functioning subscale of Short Form-36.
Implantation of PBMNCs collected after G-CSF administration could be an alternative to therapeutic angioplasty in patients with severe peripheral arterial disease.
- Circulation Research 04/2015; 116(9):1561-1578. DOI:10.1161/CIRCRESAHA.115.303565 · 11.09 Impact Factor
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ABSTRACT: Peripheral blood is a large accessible source of adult stem cells for both basic research and clinical applications. Peripheral blood mononuclear cells (PBMCs) have been reported to contain a multitude of distinct multipotent progenitor cell populations and possess the potential to differentiate into blood cells, endothelial cells, hepatocytes, cardiomyogenic cells, smooth muscle cells, osteoblasts, osteoclasts, epithelial cells, neural cells, or myofibroblasts under appropriate conditions. Furthermore, transplantation of these PBMC-derived cells can regenerate tissues and restore function after injury. This mini-review summarizes the multi-differentiation potential of PBMCs reported in the past years, discusses the possible mechanisms for this multi-differentiation potential, and describes recent techniques for efficient PBMC isolation and purification.Stem Cell Research & Therapy 11/2012; 3(6):48. DOI:10.1186/scrt139 · 4.63 Impact Factor
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ABSTRACT: Inadequate blood supply to tissues caused by obstruction of arterioles and/or capillaries results in ischemic injuries - these injuries can range from mild (eg, leg ischemia) to severe conditions (eg, myocardial infarction, stroke). Surgical and/or endovascular procedures provide cutting-edge treatment for patients with vascular disorders; however, a high percentage of patients are currently not treatable, owing to high operative risk or unfavorable vascular involvement. Therapeutic angiogenesis has recently emerged as a promising new therapy, promoting the formation of new blood vessels by the introduction of bone marrow-derived stem and progenitor cells. These cells participate in the development of new blood vessels, the enlargement of existing blood vessels, and sprouting new capillaries from existing blood vessels, providing evidence of the therapeutic utility of these cells in ischemic tissues. In this review, the authors describe peripheral arterial disease, an ischemic condition affecting the lower extremities, summarizing different aspects of vascular regeneration and discussing which and how stem cells restore the blood flow. The authors also present an overview of encouraging results from early-phase clinical trials using stem cells to treat peripheral arterial disease. The authors believe that additional research initiatives should be undertaken to better identify the nature of stem cells and that an intensive cooperation between laboratory and clinical investigators is needed to optimize the design of cell therapy trials and to maximize their scientific rigor. Only this will allow the results of these investigations to develop best clinical practices. Additionally, although a number of stem cell therapies exist, many treatments are performed outside international and national regulations and many clinical trials have been not registered on databases such as ClinicalTrials.gov or EudraCT. Therefore, more rigorous clinical trials are required to confirm the first hopeful results and to address the challenging issues.Stem Cells and Cloning: Advances and Applications 09/2012; 5:5-14. DOI:10.2147/SCCAA.S28121