Researchers have accumulated a decade of experience with autologous
cell therapy in the treatment of
critical limb ischemia (CLI). We conducted a systematic review of clinical trials in the literature to determine the safety and efficacy of
cell therapy in CLI. We searched the literature for clinical trials of autologous
cell therapy in CLI, including observational series of five or more patients to accrue a large pool of patients for safety analysis. Safety analysis included evaluation of death,
cancer, unregulated angiogenesis, and procedural adverse events such as
bleeding. Efficacy analysis included the clinical endpoints
amputation and death as well as functional and
surrogate endpoints. We identified 45 clinical trials, including seven RCTs, and 1,272 patients who received
cell therapy. The overall adverse event rate was low (4.2%).
Cell therapy patients did not have a higher mortality rate than control patients and demonstrated no increase in
cancer incidence when analyzed against population rates. With regard to efficacy,
cell therapy patients had a significantly lower
amputation rate than control patients (OR 0.36, p = 0.0004).
Cell therapy also demonstrated efficacy in a variety of functional and surrogate outcomes. Clinical trials differed in the proportion of patients with risk factors for clinical outcomes, and these influenced rates of
amputation and death.
Cell therapy presents a favorable safety profile with a low adverse event rate and no increase in severe events such as mortality and
cancer and treatment with
cell therapy decreases the risk of
amputation.
Cell therapy has a positive benefit-to-risk ratio in CLI and may be a valuable treatment option, particularly for those challenging patients who cannot undergo arterial reconstruction.