Autologous cell therapy for ischemic diabetic foot: a meta-analysis of randomized controlled trials for the development of the Italian guidelines for the treatment of diabetic foot syndrome

Alessia Scatena; Matteo Apicella; Michele Mantuano; Benedetta Ragghianti; Antonio Silverii; Cesare Miranda; Luca Monge; Luigi Uccioli; Germano Scevola; Eugenio Stabile; Mauro Gargiulo; Cristiana Vermigli; Panel of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome and on behalf of SID and AMD

doi:10.1007/s00592-024-02393-z

Autologous cell therapy for ischemic diabetic foot: a meta-analysis of randomized controlled trials for the development of the Italian guidelines for the treatment of diabetic foot syndrome

Acta Diabetol. 2024 Nov 15. doi: 10.1007/s00592-024-02393-z. Online ahead of print.

Collaborators

Panel of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome and on behalf of SID and AMD:
Matteo Monami, Corrado Bernetti, Cristina Cappella, Alessandro De Cassai, Marco Falcone, Valentina Lorenzoni, Gerardo Medea, Laura Stefanon, Rodolfo Tramonta, Antonio Volpe, Luigi Uccioli

Affiliations

¹ Diabetology Unit, Health Authorities South East Tuscany, San Donato Hospital, Via Pietro Nenni 20, 52100, Arezzo, Italy. alessia.scatena@uslsudest.toscana.it.
² Diabetology Unit, Health Authorities South East Tuscany, San Donato Hospital, Via Pietro Nenni 20, 52100, Arezzo, Italy.
³ Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy.
⁴ Pordenone Hospital, Pordenone, Italy.
⁵ AMD - Italian Association of Clinical Diabetologists, Rome, Italy.
⁶ Diabetes Section CTO Hospital and dept of Biomedicine and prevention Tor Vergata University of Rome, Rome, Italy.
⁷ Ospedale Sandro Pertini, Roma, Italy.
⁸ Azienda Ospedaliera Regionale "San Carlo", Potenza, Italy.
⁹ Vascular Surgery, University of Bologna- DIMEC, Bologna, Italy.
¹⁰ University Hospital Perugia, Perugia, Italy.

PMID: 39545964
DOI: 10.1007/s00592-024-02393-z

Abstract

Aim: To assess the efficacy and safety of autologous cell therapy (ACT) in patients with ischemic diabetic foot ulcers (DFU). The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome (DFS).

Methods: A Medline and Embase search were performed up to Feb 1st, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with ischemic foot ulcers comparing ACT with placebo/no therapy/standard of care (SoC), with a duration of at least 26 weeks. Prespecified endpoints were: major amputation (principal) and minor amputation, ulcer healing, time-to-healing, transcutaneous oxygen pressure (TcPO2), ankle-brachial index (ABI), pain, and all-cause mortality (secondary). Any ACT was allowed, irrespective of cell product type and route of administration (intra-arterial and intramuscular).

Results: Seven studies fulfilled all inclusion criteria, all using intramuscular transplantation as route of administration, but only 2 had a follow-up greater than 26 weeks. Participants treated with ACT had a significantly lower risk of major amputations in comparison with SoC/placebo (MH-OR 0.47 [0.24, 0.92], p = 0.03). ACT was also associated with a significantly higher rate of ulcer healing (MH-OR: 10.1 [3.5, 29.6], p < 0.001), greater increase of TcPO₂ and ABI values (WMD: 17.57 [13.02, 22.12], p < 0.001), and reduction of pain (WMD: -1.83 [-2.32, -1.34], p = 0.003).

Conclusions: ACT must be considered as a potential therapy for patients with ischemic diabetic foot ulcers. Further studies are needed to better clarify their role in the treatment and management of DFS.