Patients with “no-option” chronic limb-threatening ischemia (CLTI) are ineligible for standard revascularization procedures, which leads to undesirable survival outcomes.¹ Autologous cell therapy (ACT) is a novel therapeutic technique that injects mesenchymal stem cells of the patient into the lower limb intramuscularly or intra-arterially, which facilitates the secretion of anti-inflammatory cytokines from neighboring cells, the migration of macrophages, and the reduction of pro-inflammatory cytokine levels.¹ Despite having been shown to be safe and effective in previous studies, the current clinical guidelines have restricted the use of ACT for only CLTI patients enrolled in clinical trials.¹

Researchers from the Institute for Clinical and Experimental Medicine, Prague, Czech Republic, conducted a single-center, randomized controlled trial to analyze the efficacy of ACT in treating “no-option” CLTI patients with diabetes in comparison with standard treatment (ST).¹  In total, 55 eligible patients, defined as having transcutaneous oximetry (TcPO₂) <30 mmHg, gangrene, and rest pain, were enrolled and randomized to receive either ACT (n=28) or ST (n=27).¹ In the ACT group, a suspension of bone marrow mononuclear cells (BMMNC) was obtained via the centrifugation and separation of patients’ bone marrow, which was then injected into the calf and feet muscles in a series of 40 punctures.¹ After 3 months of treatment, patients in the ST group who did not require limb amputation were switched to ACT.¹ The primary endpoints of the study were changes in TcPO₂ levels at week 12 and overall amputation-free survival.¹ Other secondary endpoints assessed the effects of ACT on wound healing, pain, and overall tolerability, which included number of patients healed, changes in pain-related questionnaire scores such as the Visual Analogue Scale (VAS) and Wong-Baker Faces Pain Rating Scale (WB) at week 12, and the overall incidence of adverse events (AEs).¹

The results of the study showed that patients who received ACT experienced a significant improvement in TcPO₂ levels (p=0.004), VAS (p<0.0001), and WB scores (p<0.0001) after 3 months of treatment compared to baseline.¹ In addition, the TcPO₂ level of the ACT group was significantly higher than that of the ST group during week 12 (MD=17.9mmHg; p=0.038), with the proportion of healed patients in the ACT group being almost 7 times as high as the ST group (34.8% vs. 5.3%; p=0.008).¹

Upon switching to ACT at week 12, the ST group also experienced significant improvements in TcPO₂ levels (p=0.006), VAS (p<0.0001), and WB scores (p=0.0001) at week 24.¹ After a follow-up period of 12 months, the ACT group exhibited a numerically higher amputation-free survival rate compared to the ST group, though no statistical significance was observed.¹ Throughout the study period, ACT was well-tolerated among the study population, with only 1 patient experiencing bleeding events after bone marrow aspiration and another patient experiencing a temporary worsening of limb edema after injection.¹

In summary, this study highlighted the clinical efficacy of ACT among patients with “no option” CLTI, as capable of facilitating significant improvements in TcPO₂ levels, recovery from ulcers, and patient-reported pain without any serious AEs within 3 months.¹ While the findings from this study did not prove any difference in amputation rates after 3 months, a trend of higher amputation-free survival at 12 months was observed in ACT-treated patients.¹