Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Internal Medicine Neurology Oncology Pediatrics Respiratory Medicine Surgery
Congress Coverage
2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting

Keynote Webinar | Spotlight on Diet and Diabetes

Watch on-demand

An expert-led symposium exploring the prevention and management of type 2 diabetes through dietary interventions. 
ADVANCED SEARCH
Log in
Top
Molecular Diagnosis & Therapy
Published in: Molecular Diagnosis & Therapy 6/2023

Open Access 22-09-2023 | Diabetic Foot | Current Opinion

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

Authors: Michal Dubský, Jitka Husáková, Dominika Sojáková, Vladimíra Fejfarová, Edward B. Jude

Published in: Molecular Diagnosis & Therapy | Issue 6/2023

Login to get access

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.
Literature
1.
2.
Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet. 2005;366:1719–24. PubMedCrossRef
3.
Turns M. Diabetic foot ulcer management: the podiatrist’s perspective. Br J Community Nurs. 2013;18(Suppl):S14 ( S16-19). CrossRef
4.
Thorud JC, Plemmons B, Buckley CJ, Shibuya N, Jupiter DC. Mortality after nontraumatic major amputation among patients with diabetes and peripheral vascular disease: a systematic review. J Foot Ankle Surg. 2016;55:591–9. PubMedCrossRef
5.
Ogurtsova K, Morbach S, Haastert B, Dubsky M, Rumenapf G, Ziegler D, et al. Cumulative long-term recurrence of diabetic foot ulcers in two cohorts from centres in Germany and the Czech Republic. Diabetes Res Clin Pract. 2021;172: 108621. PubMedCrossRef
6.
Dubsky M, Jirkovska A, Bem R, Nemcova A, Fejfarova V, Jude EB. Cell therapy of critical limb ischemia in diabetic patients—state of art. Diabetes Res Clin Pract. 2017;126:263–71. PubMedCrossRef
7.
8.
Fadini GP, Agostini C, Avogaro A. Autologous stem cell therapy for peripheral arterial disease meta-analysis and systematic review of the literature. Atherosclerosis. 2010;209:10–7. CrossRef
9.
Lawall H, Bramlage P, Amann B. Stem cell and progenitor cell therapy in peripheral artery disease. A critical appraisal. Thromb Haemost. 2010;103:696–709. PubMedCrossRef
10.
Teraa M, Sprengers RW, van der Graaf Y, Peters CE, Moll FL, Verhaar MC. Autologous bone marrow-derived cell therapy in patients with critical limb ischemia: a meta-analysis of randomized controlled clinical trials. Ann Surg. 2013;258:922–9. PubMedCrossRef
11.
Panunzi A, Madotto F, Sangalli E, Riccio F, Sganzaroli AB, Galenda P, et al. 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;21:196. PubMedPubMedCentralCrossRef
12.
Meyerspeer M, Boesch C, Cameron D, Dezortova M, Forbes SC, Heerschap A, et al. (31) P magnetic resonance spectroscopy in skeletal muscle: Experts’ consensus recommendations. NMR Biomed. 2020;34: e4246. PubMedPubMedCentralCrossRef
13.
Hájek MŠP, Kovář J, Dezortová M. Dynamická in vivo 31P MR spektroskopie člověka. Chem Listy. 2017;111:516–23.
14.
Pan X, Chen G, Wu P, Han C, Ho JK. Skin perfusion pressure as a predictor of ischemic wound healing potential. Biomed Rep. 2018;8:330–4. PubMedPubMedCentral
15.
Tsuji Y, Hiroto T, Kitano I, Tahara S, Sugiyama D. Importance of skin perfusion pressure in treatment of critical limb ischemia. Wounds. 2008;20:95–100. PubMed
16.
Thomas KN, Cotter JD, Lucas SJ, Hill BG, van Rij AM. Reliability of contrast-enhanced ultrasound for the assessment of muscle perfusion in health and peripheral arterial disease. Ultrasound Med Biol. 2015;41:26–34. PubMedCrossRef
17.
Meneses AL, Nam MCY, Bailey TG, Magee R, Golledge J, Hellsten Y, et al. Leg blood flow and skeletal muscle microvascular perfusion responses to submaximal exercise in peripheral arterial disease. Am J Physiol Heart Circ Physiol. 2018;315:H1425–33. PubMedCrossRef
18.
Pu H, Huang Q, Zhang X, Wu Z, Qiu P, Jiang Y, et al. A meta-analysis of randomized controlled trials on therapeutic efficacy and safety of autologous cell therapy for atherosclerosis obliterans. J Vasc Surg. 2022;75(1440–1449): e1445.
19.
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;13:416. PubMedPubMedCentralCrossRef
20.
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;10:140. PubMedPubMedCentralCrossRef
21.
Conte MS, Bradbury AW, Kolh P, White JV, Dick F, Fitridge R, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg. 2019;69:3S-125Se140. CrossRef
22.
Nickinson ATO, Houghton JSM, Bridgwood B, Essop-Adam A, Nduwayo S, Payne T, et al. The utilisation of vascular limb salvage services in the assessment and management of chronic limb-threatening ischaemia and diabetic foot ulceration: A systematic review. Diabetes Metab Res Rev. 2020;36: e3326. CrossRef
23.
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. PubMedPubMedCentralCrossRef
24.
Neagu C, Buzea A, Agache A, Georgescu D, Patrascu T. Surgical revascularization in chronic limb-threatening ischemia in diabetic patients. Chirurgia (Bucur). 2018;113:668–77. PubMedCrossRef
25.
Dalla Paola L, Cimaglia P, Carone A, Scavone G, Boscarino G, Bernucci D, et al. Limb salvage in diabetic patients with no-option critical limb ischemia: outcomes of a specialized center experience. Diabet Foot Ankle. 2019;10:1696012. PubMedPubMedCentralCrossRef
26.
Soria-Juan B, Escacena N, Capilla-Gonzalez V, Aguilera Y, Llanos L, Tejedo JR, et al. Cost-effective, safe, and personalized cell therapy for critical limb ischemia in type 2 diabetes mellitus. Front Immunol. 2019;10:1151. PubMedPubMedCentralCrossRef
27.
Xie B, Luo H, Zhang Y, Wang Q, Zhou C, Xu D. Autologous stem cell therapy in critical limb ischemia: a meta-analysis of randomized controlled trials. Stem Cells Int. 2018;2018:7528464. PubMedPubMedCentralCrossRef
28.
Pysna A, Bem R, Nemcova A, Fejfarova V, Jirkovska A, Hazdrova J, et al. Endothelial progenitor cells biology in diabetes mellitus and peripheral arterial disease and their therapeutic potential. Stem Cell Rev Rep. 2019;15:157–65. PubMedCrossRef
29.
Fadini GP, Ferraro F, Quaini F, Asahara T, Madeddu P. Concise review: diabetes, the bone marrow niche, and impaired vascular regeneration. Stem Cells Transl Med. 2014;3:949–57. PubMedPubMedCentralCrossRef
30.
Fadini GP, Spinetti G, Santopaolo M, Madeddu P. Impaired regeneration contributes to poor outcomes in diabetic peripheral artery disease. Arterioscler Thromb Vasc Biol. 2020;40:34–44. PubMedCrossRef
31.
Cianfarani F, Toietta G, Di Rocco G, Cesareo E, Zambruno G, Odorisio T. Diabetes impairs adipose tissue-derived stem cell function and efficiency in promoting wound healing. Wound Repair Regen. 2013;21:545–53. PubMedCrossRef
32.
Inoue O, Usui S, Takashima SI, Nomura A, Yamaguchi K, Takeda Y, et al. Diabetes impairs the angiogenic capacity of human adipose-derived stem cells by reducing the CD271(+) subpopulation in adipose tissue. Biochem Biophys Res Commun. 2019;517:369–75. PubMedCrossRef
33.
Alshoubaki YK, Nayer B, Das S, Martino MM. Modulation of the activity of stem and progenitor cells by immune cells. Stem Cells Transl Med. 2022;11:248–58. PubMedPubMedCentralCrossRef
34.
35.
Mennes OA, van Netten JJ, van Baal JG, Steenbergen W. Assessment of microcirculation in the diabetic foot with laser speckle contrast imaging. Physiol Meas. 2019;40: 065002. PubMedCrossRef
36.
Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002;360:427–35. PubMedCrossRef
37.
Hinchliffe RJ, Forsythe RO, Apelqvist J, Boyko EJ, Fitridge R, Hong JP, et al. Guidelines on diagnosis, prognosis, and management of peripheral artery disease in patients with foot ulcers and diabetes (IWGDF 2019 update). Diabetes Metab Res Rev. 2020;36(Suppl 1): e3276. PubMedCrossRef
38.
Fejfarova V, Matuska J, Jude E, Pithova P, Flekac M, Roztocil K, et al. Stimulation TcPO2 testing improves diagnosis of peripheral arterial disease in patients with diabetic foot. Front Endocrinol (Lausanne). 2021;12: 744195. PubMedCrossRef
39.
Kalani M, Brismar K, Fagrell B, Ostergren J, Jorneskog G. Transcutaneous oxygen tension and toe blood pressure as predictors for outcome of diabetic foot ulcers. Diabetes Care. 1999;22:147–51. PubMedCrossRef
40.
Klepanec A, Mistrik M, Altaner C, Valachovicova M, Olejarova I, Slysko R, et al. No difference in intra-arterial and intramuscular delivery of autologous bone marrow cells in patients with advanced critical limb ischemia. Cell Transplant. 2012;21:1909–18. PubMedCrossRef
41.
Dubsky M, Jirkovska A, Bem R, Fejfarova V, Pagacova L, Sixta B, et al. Both autologous bone marrow mononuclear cell and peripheral blood progenitor cell therapies similarly improve ischaemia in patients with diabetic foot in comparison with control treatment. Diabetes Metab Res Rev. 2013;29:369–76. PubMedCrossRef
42.
43.
44.
Powell RJ, Comerota AJ, Berceli SA, Guzman R, Henry TD, Tzeng E, et al. Interim analysis results from the RESTORE-CLI, a randomized, double-blind multicenter phase II trial comparing expanded autologous bone marrow-derived tissue repair cells and placebo in patients with critical limb ischemia. J Vasc Surg. 2011;54:1032–41. PubMedCrossRef
45.
Chruewkamlow N, Pruekprasert K, Phutthakunphithak P, Acharayothin O, Prapassaro T, Hongku K, et al. Novel culture media enhances mononuclear cells from patients with chronic limb-threatening ischemia to increase vasculogenesis and anti-inflammatory effect. Stem Cell Res Ther. 2021;12:520. PubMedPubMedCentralCrossRef
46.
Rehak L, Giurato L, Meloni M, Panunzi A, Manti GM, Uccioli L. The immune-centric revolution in the diabetic foot: monocytes and lymphocytes role in wound healing and tissue regeneration—a narrative review. J Clin Med. 2022;11(3):889. https://​doi.​org/​10.​3390/​jcm11030889. PMID: 35160339; PMCID: PMC8836882.
47.
Walter DH, Krankenberg H, Balzer JO, Kalka C, Baumgartner I, Schluter M, et al. Intraarterial administration of bone marrow mononuclear cells in patients with critical limb ischemia: a randomized-start, placebo-controlled pilot trial (PROVASA). Circ Cardiovasc Interv. 2011;4:26–37. PubMedCrossRef
48.
Teraa M, Sprengers RW, Schutgens RE, Slaper-Cortenbach IC, van der Graaf Y, Algra A, et al. Effect of repetitive intra-arterial infusion of bone marrow mononuclear cells in patients with no-option limb ischemia: the randomized, double-blind, placebo-controlled Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial. Circulation. 2015;131:851–60. PubMedCrossRef
49.
Pignon B, Sevestre MA, Kanagaratnam L, Pernod G, Stephan D, Emmerich J, et al. Autologous bone marrow mononuclear cell implantation and its impact on the outcome of patients with critical limb ischemia—results of a randomized, double-blind, placebo-controlled trial. Circ J. 2017;81:1713–20. PubMedCrossRef
50.
Powell RJ, Marston WA, Berceli SA, Guzman R, Henry TD, Longcore AT, et al. Cellular therapy with Ixmyelocel-T to treat critical limb ischemia: the randomized, double-blind, placebo-controlled RESTORE-CLI trial. Mol Ther. 2012;20:1280–6. PubMedPubMedCentralCrossRef
51.
Molavi B, Zafarghandi MR, Aminizadeh E, Hosseini SE, Mirzayi H, Arab L, et al. Safety and efficacy of repeated bone marrow mononuclear cell therapy in patients with critical limb ischemia in a pilot randomized controlled trial. Arch Iran Med. 2016;19:388–96. PubMed
52.
Kang WC, Oh PC, Lee K, Ahn T, Byun K. Increasing injection frequency enhances the survival of injected bone marrow derived mesenchymal stem cells in a critical limb ischemia animal model. Korean J Physiol Pharmacol. 2016;20:657–67. PubMedPubMedCentralCrossRef
53.
54.
Rigato M, Monami M, Fadini GP. Autologous cell therapy for peripheral arterial disease: systematic review and meta-analysis of randomized, nonrandomized, and noncontrolled studies. Circ Res. 2017;120:1326–40. PubMedCrossRef
55.
Wang SK, Green LA, Motaganahalli RL, Wilson MG, Fajardo A, Murphy MP. Rationale and design of the MarrowStim PAD Kit for the Treatment of Critical Limb Ischemia in Subjects with Severe Peripheral Arterial Disease (MOBILE) trial investigating autologous bone marrow cell therapy for critical limb ischemia. J Vasc Surg. 2017;65(1850–1857): e1852.
56.
Lehalle BJP, Stoltz JF. Diabetic patients on Rutherford’s stage 5 is the best indication of stem cell therapy in peripheral artery disease: a retrospective study on 367 patients. J Cell Immunother. 2018;4:18–21. CrossRef
57.
Karetova D, Seifert B, Vojtiskova J, Roztocil K, Cifkova R. The Czech ABI Project—prevalence of peripheral arterial disease in patients at risk using the ankle-brachial index in general practice (a cross-sectional study). Neuro Endocrinol Lett. 2012;33(Suppl 2):32–7. PubMed
58.
Young MJ, McCardle JE, Randall LE, Barclay JI. Improved survival of diabetic foot ulcer patients 1995–2008: possible impact of aggressive cardiovascular risk management. Diabetes Care. 2008;31:2143–7. PubMedPubMedCentralCrossRef
59.
Persiani F, Paolini A, Camilli D, Mascellari L, Platone A, Magenta A, et al. Peripheral blood mononuclear cells therapy for treatment of lower limb ischemia in diabetic patients: a single-center experience. Ann Vasc Surg. 2018;53:190–6. PubMedCrossRef
60.
61.
Kolvenbach R, Kreissig C, Cagiannos C, Afifi R, Schmaltz E. Intraoperative adjunctive stem cell treatment in patients with critical limb ischemia using a novel point-of-care device. Ann Vasc Surg. 2010;24:367–72. PubMedCrossRef
62.
Teng YC, Porfirio-Sousa AL, Ribeiro GM, Arend MC, da Silva ML, Chen ES, et al. Analyses of the pericyte transcriptome in ischemic skeletal muscles. Stem Cell Res Ther. 2021;12:183. PubMedPubMedCentralCrossRef
63.
Bolli R, Chugh AR, D’Amario D, Loughran JH, Stoddard MF, Ikram S, et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet. 2011;378:1847–57. PubMedPubMedCentralCrossRef
64.
Hu S, Liu S, Zheng Z, Yuan X, Li L, Lu M, et al. Isolated coronary artery bypass graft combined with bone marrow mononuclear cells delivered through a graft vessel for patients with previous myocardial infarction and chronic heart failure: a single-center, randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol. 2011;57:2409–15. PubMedCrossRef
65.
Meloni M, Giurato L, Izzo V, Stefanini M, Pampana E, Gandini R, et al. Long term outcomes of diabetic haemodialysis patients with critical limb ischemia and foot ulcer. Diabetes Res Clin Pract. 2016;116:117–22. PubMedCrossRef
66.
Biancari F, Arvela E, Korhonen M, Soderstrom M, Halmesmaki K, Alback A, et al. End-stage renal disease and critical limb ischemia: a deadly combination? Scand J Surg. 2012;101:138–43. PubMedCrossRef
67.
Dubsky M, Jirkovska A, Bem R, Nemcova A, Fejfarova V, Hazdrova J, et al. Impact of severe diabetic kidney disease on the clinical outcome of autologous cell therapy in people with diabetes and critical limb ischaemia. Diabet Med. 2019;36:1133–40. PubMedCrossRef
68.
Herzog CA, Asinger RW, Berger AK, Charytan DM, Diez J, Hart RG, et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011;80:572–86. PubMedCrossRef
69.
Garimella PS, Balakrishnan P, Correa A, Poojary P, Annapureddy N, Chauhan K, et al. Nationwide trends in hospital outcomes and utilization after lower limb revascularization in patients on hemodialysis. JACC Cardiovasc Interv. 2017;10:2101–10. PubMedPubMedCentralCrossRef
70.
Dubsky M, Fejfarova V, Bem R, Jirkovska A, Nemcova A, Sutoris K, et al. Main factors predicting nonresponders to autologous cell therapy for critical limb ischemia in patients with diabetic foot. Angiology. 2021;72:861–6. PubMedCrossRef
71.
Liotta F, Annunziato F, Castellani S, Boddi M, Alterini B, Castellini G, et al. therapeutic efficacy of autologous non-mobilized enriched circulating endothelial progenitors in patients with critical limb ischemia—the SCELTA Trial. Circ J. 2018;82:1688–98. PubMedCrossRef
72.
Moriya J, Minamino T, Tateno K, Shimizu N, Kuwabara Y, Sato Y, et al. Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia. Circ Cardiovasc Interv. 2009;2:245–54. PubMedCrossRef
73.
Gemmati D, Serino ML, Trivellato C, Fiorini S, Scapoli GL. C677T substitution in the methylenetetrahydrofolate reductase gene as a risk factor for venous thrombosis and arterial disease in selected patients. Haematologica. 1999;84:824–8. PubMed
74.
Pan T, Liu H, Fang Y, Wei Z, Gu S, Fang G, et al. Predictors of responders to mononuclear stem cell-based therapeutic angiogenesis for no-option critical limb ischemia. Stem Cell Res Ther. 2019;10:15. PubMedPubMedCentralCrossRef
75.
Madaric J, Klepanec A, Valachovicova M, Mistrik M, Bucova M, Olejarova I, et al. Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia. Stem Cell Res Ther. 2016;7:116. PubMedPubMedCentralCrossRef
76.
Attanasio S, Snell J. Therapeutic angiogenesis in the management of critical limb ischemia: current concepts and review. Cardiol Rev. 2009;17:115–20. PubMedCrossRef
77.
Murphy MP, Lawson JH, Rapp BM, Dalsing MC, Klein J, Wilson MG, et al. Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia. J Vasc Surg. 2011;53(1565–1574): e1561.
78.
Tongers J, Roncalli JG, Losordo DW. Therapeutic angiogenesis for critical limb ischemia: microvascular therapies coming of age. Circulation. 2008;118:9–16. PubMedCrossRef
79.
Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: an update. Cell Transplant. 2016;25:829–48. PubMedCrossRef
80.
Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013;15:641–8. PubMedPubMedCentralCrossRef
81.
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7. PubMedCrossRef
82.
Zhang JC, Zheng GF, Wu L, Ou Yang LY, Li WX. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats. Braz J Med Biol Res. 2014;47:886–94. PubMedPubMedCentralCrossRef
83.
Trounson A, McDonald C. Stem Cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17:11–22. PubMedCrossRef
84.
85.
Sui BD, Zheng CX, Li M, Jin Y, Hu CH. Epigenetic regulation of mesenchymal stem cell homeostasis. Trends Cell Biol. 2020;30:97–116. PubMedCrossRef
86.
Lu D, Chen B, Liang Z, Deng W, Jiang Y, Li S, et al. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract. 2011;92:26–36. PubMedCrossRef
87.
Huerta CT, Voza FA, Ortiz YY, Liu ZJ, Velazquez OC. Mesenchymal stem cell-based therapy for non-healing wounds due to chronic limb-threatening ischemia: a review of preclinical and clinical studies. Front Cardiovasc Med. 2023;10:1113982. PubMedPubMedCentralCrossRef
88.
89.
Kulwas A, Drela E, Jundzill W, Goralczyk B, Ruszkowska-Ciastek B, Rosc D. Circulating endothelial progenitor cells and angiogenic factors in diabetes complicated diabetic foot and without foot complications. J Diabetes Complications. 2015;29:686–90. PubMedCrossRef
90.
Shmelkov SV, St Clair R, Lyden D, Rafii S. AC133/CD133/Prominin-1. Int J Biochem Cell Biol. 2005;37:715–9. PubMedCrossRef
91.
Garrity MM, Gibbons SJ, Smyrk TC, Vanderwinden JM, Gomez-Pinilla PJ, Nehra A, et al. Diagnostic challenges of motility disorders: optimal detection of CD117+ interstitial cells of Cajal. Histopathology. 2009;54:286–94. PubMedPubMedCentralCrossRef
92.
Li PH, Liu LH, Chang CC, Gao R, Leung CH, Ma DL, et al. Silencing stem cell factor gene in fibroblasts to regulate paracrine factor productions and enhance c-Kit expression in melanocytes on melanogenesis. Int J Mol Sci. 2018;19:1475. PubMedPubMedCentralCrossRef
93.
Valli H, Sukhwani M, Dovey SL, Peters KA, Donohue J, Castro CA, et al. Fluorescence- and magnetic-activated cell sorting strategies to isolate and enrich human spermatogonial stem cells. Fertil Steril. 2014;102(566–580): e567.
94.
Duong KL, Das S, Yu S, Barr JY, Jena S, Kim E, et al. Identification of hematopoietic-specific regulatory elements from the CD45 gene and use for lentiviral tracking of transplanted cells. Exp Hematol. 2014;42(761–772):e761–e710. CrossRef
95.
Beare A, Stockinger H, Zola H, Nicholson I. Monoclonal antibodies to human cell surface antigens. Curr Protoc Immunol. 2008;Appendix 4:4A.
96.
Johnson BW, Achyut BR, Fulzele S, Mondal AK, Kolhe R, Arbab AS. Delineating pro-angiogenic myeloid cells in cancer therapy. Int J Mol Sci. 2018;19:2565. PubMedPubMedCentralCrossRef
97.
Spigoni V, Fantuzzi F, Carubbi C, Pozzi G, Masselli E, Gobbi G, et al. Sodium-glucose cotransporter 2 inhibitors antagonize lipotoxicity in human myeloid angiogenic cells and ADP-dependent activation in human platelets: potential relevance to prevention of cardiovascular events. Cardiovasc Diabetol. 2020;19:46. PubMedPubMedCentralCrossRef
98.
Wong CWT, Sawhney A, Wu Y, Mak YW, Tian XY, Chan HF, et al. Sourcing of human peripheral blood-derived myeloid angiogenic cells under xeno-free conditions for the treatment of critical limb ischemia. Stem Cell Res Ther. 2022;13:419. PubMedPubMedCentralCrossRef
99.
de la Puente P, Muz B, Azab F, Azab AK. Cell trafficking of endothelial progenitor cells in tumor progression. Clin Cancer Res. 2013;19:3360–8. PubMedCrossRef
100.
101.
McDonald AI, Shirali AS, Aragon R, Ma F, Hernandez G, Vaughn DA, et al. Endothelial regeneration of large vessels is a biphasic process driven by local cells with distinct proliferative capacities. Cell Stem Cell. 2018;23(210–225): e216.
102.
Singhal M, Liu X, Inverso D, Jiang K, Dai J, He H, et al. Endothelial cell fitness dictates the source of regenerating liver vasculature. J Exp Med. 2018;215:2497–508. PubMedPubMedCentralCrossRef
103.
Scatena A, Petruzzi P, Maioli F, Lucaroni F, Ambrosone C, Ventoruzzo G, et al. Autologous peripheral blood mononuclear cells for limb salvage in diabetic foot patients with no-option critical limb ischemia. J Clin Med. 2021;10:2213. PubMedPubMedCentralCrossRef
104.
Troisi N, D’Oria M, Fernandes EFJ, Angelides N, Avgerinos E, Liapis C, et al. International Union of Angiology Position Statement on no-option chronic limb threatening ischemia. Int Angiol. 2022;41:382–404. PubMedCrossRef
Metadata
Title
Cell Therapy of Severe Ischemia in People with Diabetic Foot Ulcers—Do We Have Enough Evidence?
Authors
Michal Dubský
Jitka Husáková
Dominika Sojáková
Vladimíra Fejfarová
Edward B. Jude
Publication date
22-09-2023
Publisher
Springer International Publishing
Keyword
Diabetic Foot
Published in
Molecular Diagnosis & Therapy / Issue 6/2023
Print ISSN: 1177-1062
Electronic ISSN: 1179-2000
DOI
https://doi.org/10.1007/s40291-023-00667-w

Other articles of this Issue 6/2023

Molecular Diagnosis & Therapy 6/2023 Go to the issue

Original Research Article

Clinical Potential of Expanded Noninvasive Prenatal Testing for Detection of Aneuploidies and Microdeletion/Microduplication Syndromes

Review Article

MicroRNAs Function in Dental Stem Cells as a Promising Biomarker and Therapeutic Target for Dental Diseases

Original Research Article

Personalized Cancer Monitoring Assay for the Detection of ctDNA in Patients with Solid Tumors

Review Article

Oxidative Stress and Potential Antioxidant Therapies in Vitiligo: A Narrative Review

Leading Article

Optimizing CAR-T Therapy for Glioblastoma

Review Article

Application of Nanopore Sequencing in the Diagnosis and Treatment of Pulmonary Infections
Webinar | 08-11-2023 | 18:00 (CET)

Keynote Webinar | Spotlight on Diet and Diabetes

Watch now

An expert-led symposium exploring the prevention and management of type 2 diabetes through dietary interventions. Highlights include discussion of the recent EASD guidelines, therapeutic diets, food types and processing, plus psychological factors that influence patient success, and the drivers of healthy eating and diabetes control.
Prof. Mike Lean
Prof. Falko Sniehotta
Image Credits