Progenitor Cell Therapy in Patients With Critical Limb Ischemia Without Surgical Options

2008 ◽  
Vol 247 (3) ◽  
pp. 411-420 ◽  
Author(s):  
Ralf W. Sprengers ◽  
Daniel J. Lips ◽  
Frans L. Moll ◽  
Marianne C. Verhaar
Keyword(s):  
Cell Therapy ◽  
Critical Limb Ischemia ◽  
Progenitor Cell ◽  
Limb Ischemia ◽  
Surgical Options

scholarly journals Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pegah Nammian ◽  
Seyedeh-Leili Asadi-Yousefabad ◽  
Sajad Daneshi ◽  
Mohammad Hasan Sheikhha ◽  
Seyed Mohammad Bagher Tabei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Femoral Artery ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Abstract Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

scholarly journals Cell Therapy in Patients with Critical Limb Ischemia

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Rita Compagna ◽  
Bruno Amato ◽  
Salvatore Massa ◽  
Maurizio Amato ◽  
Raffaele Grande ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Tissue Loss ◽  
Systematic Analysis ◽  
Peripheral Arterial Obstructive Disease ◽  
Peripheral Arterial ◽  
Cellular Components

Critical limb ischemia (CLI) represents the most advanced stage of peripheral arterial obstructive disease (PAOD) with a severe obstruction of the arteries which markedly reduces blood flow to the extremities and has progressed to the point of severe rest pain and/or even tissue loss. Recent therapeutic strategies have focused on restoring this balance in favor of tissue survival using exogenous molecular and cellular agents to promote regeneration of the vasculature. These are based on stimulation of angiogenesis by extracellular and cellular components. This review article carries out a systematic analysis of the most recent scientific literature on the application of stem cells in patients with CLI. The results obtained from the detailed analysis of the recent literature data have confirmed the beneficial role of cell therapy in reducing the rate of major amputations in patients with CLI and improving their quality of life.

scholarly journals Long-Term Clinical Outcomes Survey of Bone Marrow-Derived Cell Therapy in Critical Limb Ischemia in Japan

2018 ◽  
Vol 82 (4) ◽  
pp. 1168-1178 ◽  
Author(s):  
Kazuhisa Kondo ◽  
Kenji Yanishi ◽  
Ryo Hayashida ◽  
Satoshi Shintani ◽  
Rei Shibata ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Therapy ◽  
Clinical Outcomes ◽  
Critical Limb Ischemia ◽  
Limb Ischemia

Cell therapy of critical limb ischemia in diabetic patients – State of art

2017 ◽  
Vol 126 ◽  
pp. 263-271 ◽  
Author(s):  
Michal Dubský ◽  
Alexandra Jirkovská ◽  
Robert Bem ◽  
Andrea Nemcová ◽  
Vladimira Fejfarová ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Diabetic Patients ◽  
State Of Art

Abstract 119: Potential Role for Bone Marrow Niche and Endothelial Progenitor Cell Dysfunction in Critical Limb Ischemia

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Martin Teraa ◽  
Ralf W Sprengers ◽  
Frans L Moll ◽  
Marianne C Verhaar ◽  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Critical Limb Ischemia ◽  
Progenitor Cell ◽  
Limb Ischemia ◽  
Endothelial Damage ◽  
Inverse Association ◽  
Healthy Controls ◽  
Endothelial Progenitor ◽  
And Function

Background Critical limb ischemia (CLI) is characterized by obstruction of lower extremity arteries and a largely unexplained impaired ischemic neovascularization response. Bone marrow (BM) derived endothelial progenitor cells (EPC) contribute to postnatal neovascularization. We hypothesize that reduced levels and function of circulating progenitor cells and a dysfunctional BM environment contribute to impaired neovascularization in CLI. Methods Levels of primitive (CD34+ and CD133+) progenitors and CD34+KDR+ haemangioblastic EPC were analyzed using flow cytometry in peripheral blood (PB) and BM from 101 CLI patients in the JUVENTAS trial ( NCT00371371 ) and healthy controls (n=37 and n=12 for PB and BM, respectively). Endothelial damage markers (sE-selectin, sICAM-1, sVCAM-1, thrombomodulin) and PB levels of progenitor cell mobilizing (VEGF, SDF-1α, SCF, G-CSF) and inflammatory (IL-6, IL-8, IP-10) factors were assessed by ELISA and multiplex. Levels and activity of the EPC mobilizing protease MMP-9 were assessed in BM plasma by ELISA and zymography. Circulating angiogenic cells (CAC) were cultured from PB, and CAC paracrine function was assessed. Results Endothelial damage markers were higher in CLI ( p< 0.01). PB levels of VEGF, SDF-1α, SCF, G-CSF ( p< 0.05) and of IL-6, IL-8 and IP-10 were higher in CLI ( p< 0.05). Circulating EPC and CD133+ cells and BM CD34+ cells were significantly lower in CLI (all p <0.05), BM levels and activity of MMP-9 were lower in CLI (both p< 0.01). Multivariate regression analysis showed an inverse association between IL-6 levels and BM CD34+ cell levels ( p= 0.007). CAC outgrowth did not differ significantly between CLI patients and healthy controls ( p= 0.137), however CAC from CLI patients had profoundly reduced migration stimulating potential ( p< 0.0001). Conclusion CLI patients have reduced levels of circulating EPC despite profound endothelial injury and an EPC mobilizing response. Moreover, CLI patients have lower BM CD34+ cell levels, which were inversely associated with the inflammatory marker IL-6, and lower BM MMP-9 levels and activity. Our data suggest that reduced levels and function of circulating progenitor cells and BM dysfunction contribute to the defective neovascularization response in CLI.

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