Stem cell therapy for treatment of thromboangiitis obliterans (Buerger's disease)

Background

Thromboangiitis obliterans, also known as Buerger's disease, is a condition characterized by recurring progressive inflammation and clotting in small- and medium-sized arteries and veins of the hands and feet. Its cause is unknown, but it is most common in men with a history of tobacco use. It is responsible for ulcers and extreme pain in the limbs of young smokers. In many cases, mainly in patients with the most severe form, there is no possibility of improving the condition with surgery, and therefore, alternative treatments are used. Stem cell therapy is an experimental treatment performed through the implantation of cells (from bone marrow, umbilical cord, peripheral blood etc.) which are capable of becoming new blood vessels, improving local circulation and contributing to the healing of ulcers and relieving rest pain. This review assessed the effectiveness of stem cell therapy in the treatment of patients with thromboangiitis obliterans (Buerger's disease).

Key results

Only one randomized controlled study (18 participants with thromboangiitis obliterans) comparing the implantation of stem cells derived from bone marrow with placebo and standard wound dressing care was included in this review (most recent search was 17 October 2017). We identified no studies that compared stem cell therapy from different sources, stem cell therapy versus drug treatment and stem cell therapy versus sympathectomy (surgical cutting of a sympathetic nerve). The results showed a decrease in ulcer size and improvement in pain-free walking distance in the group receiving the stem cell implantation compared with the group receiving placebo and standard wound dressing care.

Outcomes such as rate of amputation, pain, amputation-free survival and adverse effects were not assessed.

Quality of the evidence

We classified the quality of evidence as very low, because there was only one study, small numbers of participants, and high risk of bias in many domains and missing information regarding tobacco exposure status.

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 improving 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' 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.

Read the full 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 strategy: 

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.

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