Daniel G Cacione1, Frederico do Carmo Novaes, Daniel H Moreno. 1. Division of Vascular and Endovascular Surgery, Department of Surgery, UNIFESP - Escola Paulista de Medicina, Rua Borges Lagoa, 564 cj 124, Vila Clementino, São Paulo, Brazil, 04038000.
Abstract
BACKGROUND: Thromboangiitis obliterans, also known as Buerger's disease, is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small- and medium-sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Stem cell therapy is an option for patients with severe complications, such as ischemic ulcers or rest pain. OBJECTIVES: To assess the effectiveness and safety of stem cell therapy in individuals with thromboangiitis obliterans (Buerger's disease). SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 October 2017. The review authors searched the European grey literature OpenGrey Database, screened reference lists of relevant studies and contacted study authors. SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs of stem cell therapy in thromboangiitis obliterans (Buerger's disease). DATA COLLECTION AND ANALYSIS: The review authors (DC, DM, FN) independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: We only included one RCT (18 participants with thromboangiitis obliterans) comparing the implantation of stem cell derived from bone marrow with placebo and standard wound dressing care in this review. We identified no studies that compared stem cell therapy (bone marrow source) versus stem cell therapy (umbilical cord source), stem cell therapy (any source) versus pharmacological treatment and stem cell therapy (any source) versus sympathectomy. Ulcer healing was assessed in the form of ulcer size. The mean ulcer area decreased more in the stem cell implantation group: from 5.04 cm2 (standard deviation (SD) 0.70) to 1.48 cm2 (SD 0.56) compared with the control group: mean ulcer size area decreased from 4.68 cm2 (SD 0.62) to 3.59 cm2 (SD 0.14); mean difference (MD) -2.11 cm2, 95% confidence interval (CI) -2.49 to -1.73; 1 study, 18 participants; very low-quality evidence. Pain-free walking distance showed more of an improvement in the stem cell implantation group: from mean of 38.33 meters (SD 17.68) to 284.44 meters (SD 212.12) compared with the control group: mean walking distance increased from 35.66 meters (SD 19.79) to 78.22 meters (SD 35.35); MD 206.22 meters, 95% CI 65.73 to 346.71; 1 study; 18 participants; very low-quality evidence.Outcomes such as rate of amputation, pain, amputation-free survival and adverse effects were not assessed.The quality of evidence was classified as very low, with only one study, small numbers of participants, high risk of bias in many domains and missing information regarding tobacco exposure status. AUTHORS' CONCLUSIONS: Very low-quality evidence suggests there may be an effect of the use of bone marrow-derived stem cells in the healing of ulcers and improvement in the pain-free walking distance in patients with Buerger's disease. High-quality trials assessing the effectiveness of stem cell therapy for treatment of patients with thromboangiitis obliterans (Buerger's disease) are needed.
BACKGROUND: Thromboangiitis obliterans, also known as Buerger's disease, is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small- and medium-sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Stem cell therapy is an option for patients with severe complications, such as ischemic ulcers or rest pain. OBJECTIVES: To assess the effectiveness and safety of stem cell therapy in individuals with thromboangiitis obliterans (Buerger's disease). SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 October 2017. The review authors searched the European grey literature OpenGrey Database, screened reference lists of relevant studies and contacted study authors. SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs of stem cell therapy in thromboangiitis obliterans (Buerger's disease). DATA COLLECTION AND ANALYSIS: The review authors (DC, DM, FN) independently assessed the studies, extracted data and performed data analysis. MAIN RESULTS: We only included one RCT (18 participants with thromboangiitis obliterans) comparing the implantation of stem cell derived from bone marrow with placebo and standard wound dressing care in this review. We identified no studies that compared stem cell therapy (bone marrow source) versus stem cell therapy (umbilical cord source), stem cell therapy (any source) versus pharmacological treatment and stem cell therapy (any source) versus sympathectomy. Ulcer healing was assessed in the form of ulcer size. The mean ulcer area decreased more in the stem cell implantation group: from 5.04 cm2 (standard deviation (SD) 0.70) to 1.48 cm2 (SD 0.56) compared with the control group: mean ulcer size area decreased from 4.68 cm2 (SD 0.62) to 3.59 cm2 (SD 0.14); mean difference (MD) -2.11 cm2, 95% confidence interval (CI) -2.49 to -1.73; 1 study, 18 participants; very low-quality evidence. Pain-free walking distance showed more of an improvement in the stem cell implantation group: from mean of 38.33 meters (SD 17.68) to 284.44 meters (SD 212.12) compared with the control group: mean walking distance increased from 35.66 meters (SD 19.79) to 78.22 meters (SD 35.35); MD 206.22 meters, 95% CI 65.73 to 346.71; 1 study; 18 participants; very low-quality evidence.Outcomes such as rate of amputation, pain, amputation-free survival and adverse effects were not assessed.The quality of evidence was classified as very low, with only one study, small numbers of participants, high risk of bias in many domains and missing information regarding tobacco exposure status. AUTHORS' CONCLUSIONS: Very low-quality evidence suggests there may be an effect of the use of bone marrow-derived stem cells in the healing of ulcers and improvement in the pain-free walking distance in patients with Buerger's disease. High-quality trials assessing the effectiveness of stem cell therapy for treatment of patients with thromboangiitis obliterans (Buerger's disease) are needed.
Authors: David Atkins; Dana Best; Peter A Briss; Martin Eccles; Yngve Falck-Ytter; Signe Flottorp; Gordon H Guyatt; Robin T Harbour; Margaret C Haugh; David Henry; Suzanne Hill; Roman Jaeschke; Gillian Leng; Alessandro Liberati; Nicola Magrini; James Mason; Philippa Middleton; Jacek Mrukowicz; Dianne O'Connell; Andrew D Oxman; Bob Phillips; Holger J Schünemann; Tessa Tan-Torres Edejer; Helena Varonen; Gunn E Vist; John W Williams; Stephanie Zaza Journal: BMJ Date: 2004-06-19
Authors: T Asahara; T Murohara; A Sullivan; M Silver; R van der Zee; T Li; B Witzenbichler; G Schatteman; J M Isner Journal: Science Date: 1997-02-14 Impact factor: 47.728
Authors: C Kalka; H Masuda; T Takahashi; W M Kalka-Moll; M Silver; M Kearney; T Li; J M Isner; T Asahara Journal: Proc Natl Acad Sci U S A Date: 2000-03-28 Impact factor: 11.205