BACKGROUND AND OBJECTIVES: Half of patients with critical limb ischemia (CLI) are ineligible for revascularization at diagnosis. The aim of this study was to assess the safety and feasibility of intramuscular human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) therapy in patients with CLI due to atherosclerosis obliterans (ASO) or thromboangiitis obliterans (TAO). METHODS AND RESULTS: A total of eight patients (all male, median age 52 years, range 31∼77) with CLI were enrolled in this phase I trial. All patients were considered ineligible for further revascularization to improve CLI. We injected 1×10(7) hUCB-MSCs per single dose intramuscularly into the affected limb. The primary end points of safety were occurrence of adverse events (procedure-related complication, allergic reaction to hUCB-MSCs, graft-versus-host disease, cardiovascular and cerebrovascular events) and improvement of symptoms/clinical parameters (healing of foot ulcer, ankle-brachial index, and pain-free walking distance). Angiogenesis was measured with conventional angiography and scored by an independent reviewer. There were four adverse events in three patients. One patient, developed whole body urticaria after injection on treatment day, which disappeared after one day of antihistamine treatment. The other adverse events included diarrhea, oral ulceration, and elevation of serum creatinine level; all conditions improved without treatment. Abnormal results of laboratory parameters were not detected in any patients. Three of four ulcerations (75%) healed completely. Angiographic scores increased in three of eight patients. CONCLUSIONS: This phase I study demonstrates that intramuscular hUCB-MSC injection is a safe and well tolerated treatment for patients with end-stage CLI due to ASO and TAO.
BACKGROUND AND OBJECTIVES: Half of patients with critical limb ischemia (CLI) are ineligible for revascularization at diagnosis. The aim of this study was to assess the safety and feasibility of intramuscular human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) therapy in patients with CLI due to atherosclerosis obliterans (ASO) or thromboangiitis obliterans (TAO). METHODS AND RESULTS: A total of eight patients (all male, median age 52 years, range 31∼77) with CLI were enrolled in this phase I trial. All patients were considered ineligible for further revascularization to improve CLI. We injected 1×10(7) hUCB-MSCs per single dose intramuscularly into the affected limb. The primary end points of safety were occurrence of adverse events (procedure-related complication, allergic reaction to hUCB-MSCs, graft-versus-host disease, cardiovascular and cerebrovascular events) and improvement of symptoms/clinical parameters (healing of foot ulcer, ankle-brachial index, and pain-free walking distance). Angiogenesis was measured with conventional angiography and scored by an independent reviewer. There were four adverse events in three patients. One patient, developed whole body urticaria after injection on treatment day, which disappeared after one day of antihistamine treatment. The other adverse events included diarrhea, oral ulceration, and elevation of serum creatinine level; all conditions improved without treatment. Abnormal results of laboratory parameters were not detected in any patients. Three of four ulcerations (75%) healed completely. Angiographic scores increased in three of eight patients. CONCLUSIONS: This phase I study demonstrates that intramuscular hUCB-MSC injection is a safe and well tolerated treatment for patients with end-stage CLI due to ASO and TAO.
Authors: Anthony J Comerota; Richard C Throm; Kathryn A Miller; Timothy Henry; Nicolas Chronos; John Laird; Rafael Sequeira; Craig K Kent; Matthew Bacchetta; Corey Goldman; Juha-Pekka Salenius; Frank A Schmieder; Richard Pilsudski Journal: J Vasc Surg Date: 2002-05 Impact factor: 4.268
Authors: Emile R Mohler; Sanjay Rajagopalan; Jeffrey W Olin; Jeffrey D Trachtenberg; Henrik Rasmussen; Raphael Pak; Ronald G Crystal Journal: Vasc Med Date: 2003 Impact factor: 3.239
Authors: Sanjay Rajagopalan; Emile R Mohler; Robert J Lederman; Farrell O Mendelsohn; Jorge F Saucedo; Corey K Goldman; John Blebea; Jennifer Macko; Paul D Kessler; Henrik S Rasmussen; Brian H Annex Journal: Circulation Date: 2003-09-22 Impact factor: 29.690
Authors: Áron Szepesi; Zsolt Matula; Anna Szigeti; György Várady; József Szalma; Gyula Szabó; Ferenc Uher; Balázs Sarkadi; Katalin Német Journal: Stem Cells Int Date: 2016-11-24 Impact factor: 5.443
Authors: Bárbara Soria-Juan; Natalia Escacena; Vivian Capilla-González; Yolanda Aguilera; Lucía Llanos; Juan R Tejedo; Francisco J Bedoya; Verónica Juan; Antonio De la Cuesta; Rafael Ruiz-Salmerón; Enrique Andreu; Lukas Grochowicz; Felipe Prósper; Fermín Sánchez-Guijo; Francisco S Lozano; Manuel Miralles; Lourdes Del Río-Solá; Gregorio Castellanos; José M Moraleda; Robert Sackstein; Mariano García-Arranz; Damián García-Olmo; Franz Martín; Abdelkrim Hmadcha; Bernat Soria Journal: Front Immunol Date: 2019-06-04 Impact factor: 7.561