Critical limb ischaemia (CLI) occurs when blood flow to the legs is reduced because of the worsening of peripheral arterial disease. Initially, patients experience cramping leg pain that limits walking (termed intermittent claudication), but over time some patients experience more severe symptoms including pain at rest, leg ulceration and gangrene. The available treatment options are very limited when the disease reaches this stage, especially when surgical or catheter revascularisation is not an option. A substantial proportion of these patients require amputation of the affected limb. A new therapy (mononuclear cell therapy using the patient’s own cells) offers the possibility of an alternative treatment for patients, by supplying cells that could stimulate the formation of stable capillary vessels to improve the blood flow in the affected limb. These cells can be obtained from the bone marrow or from peripheral blood following subcutaneous injections (of granulocyte colony-stimulating factor) for five days. They are then treated in a laboratory and injected into the large muscle at the back of the lower leg.
The review authors identified only two small randomised controlled trials with a combined total of 57 patients testing the safety and effectiveness of this treatment. The findings were inconsistent. In one trial pain at rest, pain-free walking distance, ankle-brachial blood pressure index and the number of amputations all clearly improved in the group receiving mononuclear cell implantation. In the other trial only the number of amputations showed a significant improvement in the treatment group compared with the control group. The two included studies differed from each other in how they obtained the cells for injection and assessed the clinical effects at different time points, up to three months in one trial and six months in the other. They were classified as having a moderate risk of bias with unclear issues regarding their methods. No deaths were reported during the study period.