Cell Therapy of Severe Ischemia in People with Diabetic Foot Ulcers-Do We Have Enough Evidence?

Overview

Journal Mol Diagn Ther

Specialties Molecular Biology
Pathology
Pharmacology

Date 2023 Sep 22

PMID 37740111

Authors

Michal Dubsky

Jitka Husakova

Dominika Sojakova

Vladimira Fejfarova

Edward B Jude

Affiliations

Soon will be listed here.

Abstract

This current opinion article critically evaluates the efficacy of autologous cell therapy (ACT) for chronic limb-threatening ischemia (CLTI), especially in people with diabetes who are not candidates for standard revascularization. This treatment approach has been used in 'no-option' CLTI in the last two decades and more than 1700 patients have received ACT worldwide. Here we analyze the level of published evidence of ACT as well as our experience with this treatment method. Many studies have shown that ACT is safe and an effective method for patients with the most severe lower limb ischemia. However, some trials did not show any benefit of ACT, and there is some heterogeneity in the types of injected cells, route of administration and assessed endpoints. Nevertheless, we believe that ACT plays an important role in a comprehensive treatment of patients with diabetic foot and severe ischemia.

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References

Ahmad E, Lim S, Lamptey R, Webb D, Davies M . Type 2 diabetes. Lancet. 2022; 400(10365):1803-1820. DOI: 10.1016/S0140-6736(22)01655-5. View

Boulton A, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J . The global burden of diabetic foot disease. Lancet. 2005; 366(9498):1719-24. DOI: 10.1016/S0140-6736(05)67698-2. View

Thorud J, Plemmons B, Buckley C, Shibuya N, Jupiter D . Mortality After Nontraumatic Major Amputation Among Patients With Diabetes and Peripheral Vascular Disease: A Systematic Review. J Foot Ankle Surg. 2016; 55(3):591-9. DOI: 10.1053/j.jfas.2016.01.012. View

Ogurtsova K, Morbach S, Haastert B, Dubsky M, Rumenapf G, Ziegler D . Cumulative long-term recurrence of diabetic foot ulcers in two cohorts from centres in Germany and the Czech Republic. Diabetes Res Clin Pract. 2020; 172:108621. DOI: 10.1016/j.diabres.2020.108621. View

Dubsky M, Jirkovska A, Bem R, Nemcova A, Fejfarova V, Jude E . Cell therapy of critical limb ischemia in diabetic patients - State of art. Diabetes Res Clin Pract. 2017; 126:263-271. DOI: 10.1016/j.diabres.2017.02.028. View

Mheid I, Quyyumi A . Cell therapy in peripheral arterial disease. Angiology. 2008; 59(6):705-16. DOI: 10.1177/0003319708321584. View

Lawall H, Bramlage P, Amann B . Stem cell and progenitor cell therapy in peripheral artery disease. A critical appraisal. Thromb Haemost. 2010; 103(4):696-709. DOI: 10.1160/TH09-10-0688. View

Teraa M, Sprengers R, van der Graaf Y, Peters C, Moll F, Verhaar M . Autologous bone marrow-derived cell therapy in patients with critical limb ischemia: a meta-analysis of randomized controlled clinical trials. Ann Surg. 2013; 258(6):922-9. DOI: 10.1097/SLA.0b013e3182854cf1. View

Panunzi A, Madotto F, Sangalli E, Riccio F, Sganzaroli A, Galenda P . Results of a prospective observational study of autologous peripheral blood mononuclear cell therapy for no-option critical limb-threatening ischemia and severe diabetic foot ulcers. Cardiovasc Diabetol. 2022; 21(1):196. PMC: 9516816. DOI: 10.1186/s12933-022-01629-y. View

10.

Meyerspeer M, Boesch C, Cameron D, Dezortova M, Forbes S, Heerschap A . P magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations. NMR Biomed. 2020; :e4246. PMC: 8243949. DOI: 10.1002/nbm.4246. View

11.

Pan X, Chen G, Wu P, Han C, Ho J . Skin perfusion pressure as a predictor of ischemic wound healing potential. Biomed Rep. 2018; 8(4):330-334. PMC: 5838289. DOI: 10.3892/br.2018.1064. View

12.

Tsuji Y, Hiroto T, Kitano I, Tahara S, Sugiyama D . Importance of skin perfusion pressure in treatment of critical limb ischemia. Wounds. 2015; 20(4):95-100. View

13.

Thomas K, Cotter J, Lucas S, Hill B, van Rij A . Reliability of contrast-enhanced ultrasound for the assessment of muscle perfusion in health and peripheral arterial disease. Ultrasound Med Biol. 2014; 41(1):26-34. DOI: 10.1016/j.ultrasmedbio.2014.06.012. View

14.

Meneses A, Nam M, Bailey T, Magee R, Golledge J, Hellsten Y . Leg blood flow and skeletal muscle microvascular perfusion responses to submaximal exercise in peripheral arterial disease. Am J Physiol Heart Circ Physiol. 2018; 315(5):H1425-H1433. DOI: 10.1152/ajpheart.00232.2018. View

15.

Sun Y, Zhao J, Zhang L, Li Z, Lei S . Effectiveness and safety of stem cell therapy for diabetic foot: a meta-analysis update. Stem Cell Res Ther. 2022; 13(1):416. PMC: 9375292. DOI: 10.1186/s13287-022-03110-9. View

16.

Gao W, Chen D, Liu G, Ran X . Autologous stem cell therapy for peripheral arterial disease: a systematic review and meta-analysis of randomized controlled trials. Stem Cell Res Ther. 2019; 10(1):140. PMC: 6528204. DOI: 10.1186/s13287-019-1254-5. View

17.

Uccioli L, Meloni M, Izzo V, Giurato L, Merolla S, Gandini R . Critical limb ischemia: current challenges and future prospects. Vasc Health Risk Manag. 2018; 14:63-74. PMC: 5927064. DOI: 10.2147/VHRM.S125065. View

18.

Neagu C, Buzea A, Agache A, Georgescu D, Patrascu T . Surgical Revascularization in Chronic Limb-threatening Ischemia in Diabetic Patients. Chirurgia (Bucur). 2018; 113(5):668-677. DOI: 10.21614/chirurgia.113.5.668. View

19.

Paola L, Cimaglia P, Carone A, Scavone G, Boscarino G, Bernucci D . Limb salvage in diabetic patients with no-option critical limb ischemia: outcomes of a specialized center experience. Diabet Foot Ankle. 2019; 10(1):1696012. PMC: 6896489. DOI: 10.1080/2000625X.2019.1696012. View

20.

Soria-Juan B, Escacena N, Capilla-Gonzalez V, Aguilera Y, Llanos L, Tejedo J . Cost-Effective, Safe, and Personalized Cell Therapy for Critical Limb Ischemia in Type 2 Diabetes Mellitus. Front Immunol. 2019; 10:1151. PMC: 6558400. DOI: 10.3389/fimmu.2019.01151. View