Impact of severe diabetic kidney disease on the clinical outcome of autologous cell therapy in people with diabetes and critical limb ischaemia

Abstract

Aim To assess the impact of autologous cell therapy on critical limb ischaemia in people with diabetes and diabetic kidney disease. Methods A total of 59 people with diabetes (type 1 or type 2) and critical limb ischaemia, persisting after standard revascularization, were treated with cell therapy in our foot clinic over 7 years; this group comprised 17 people with and 42 without severe diabetic kidney disease. The control group had the same inclusion criteria, but was treated conservatively and comprised 21 people with and 23 without severe diabetic kidney disease. Severe diabetic kidney disease was defined as chronic kidney disease stages 4–5 (GFR <30 ml/min/1.73 m²). Death and amputation‐free survival were assessed during the 18‐month follow‐up; changes in transcutaneous oxygen pressure were evaluated at 6 and 12 months after cell therapy. Results Transcutaneous oxygen pressure increased significantly in both groups receiving cell therapy compared to baseline (both P<0.01); no significant change in either of the control groups was observed. The cell therapy severe diabetic kidney disease group had a significantly longer amputation‐free survival time compared to the severe diabetic kidney disease control group (hazard ratio 0.36, 95% CI 0.14–0.91; P=0.042); there was no difference in the non‐severe diabetic kidney disease groups. The severe diabetic kidney disease control group had a tendency to have higher mortality (hazard ratio 2.82, 95% CI 0.81–9.80; P=0.062) than the non‐severe diabetic kidney disease control group, but there was no difference between the severe diabetic kidney disease and non‐severe diabetic kidney disease cell therapy groups. Conclusions The present study shows that autologous cell therapy in people with severe diabetic kidney disease significantly improved critical limb ischaemia and lengthened amputation‐free survival in comparison with conservative treatment; however, the treatment did not influence overall survival.

Report of a phase 1 clinical trial for safety assessment of human placental mesenchymal stem cells therapy in patients with critical limb ischemia (CLI)

“…In contrast, the immunological profiles of patients with CLI did not significantly differ between baseline and the 6-month follow-up, suggesting that the delivery of allogeneic P-MSCs was completely safe. This finding is consistent with prior safety findings from comparable clinical studies [ 42 – 47 ].…”

Report of a phase 1 clinical trial for safety assessment of human placental mesenchymal stem cells therapy in patients with Critical limb ischemia (CLI)

“…The immunological pro les of patients with CLI did not signi cantly differ between baseline and the 6-month follow-up, suggesting that the delivery of allogeneic P-MSCs was completely safe. This nding is consistent with prior safety ndings from comparable clinical studies (42)(43)(44)(45)(46)(47).…”

Autologous bone marrow mesenchymal stromal cell therapy for “no-option” critical limb ischemia is limited by karyotype abnormalities

“…The results of this study confirmed that intramuscular autologous transplantation of MSCs to no-option CLI patients is safe, with no adverse events or SAEs attributable to BM harvest, cell therapy or injection procedure. This result supports the preexisting safety data reported by previous similar clinical trials [7,9,11,[21][22][23]. In this study, two cell doses were examined (20 and 40 million MSCs), with three patients treated with the low-dose and one patient treated with the higher dose.…”