Skip to main content
Top
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.
go back to reference Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet. 2005;366:1719–24.PubMedCrossRef Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet. 2005;366:1719–24.PubMedCrossRef
3.
go back to reference Turns M. Diabetic foot ulcer management: the podiatrist’s perspective. Br J Community Nurs. 2013;18(Suppl):S14 (S16-19).CrossRef Turns M. Diabetic foot ulcer management: the podiatrist’s perspective. Br J Community Nurs. 2013;18(Suppl):S14 (S16-19).CrossRef
4.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Hájek MŠP, Kovář J, Dezortová M. Dynamická in vivo 31P MR spektroskopie člověka. Chem Listy. 2017;111:516–23. Hájek MŠP, Kovář J, Dezortová M. Dynamická in vivo 31P MR spektroskopie člověka. Chem Listy. 2017;111:516–23.
14.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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. 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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
35.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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
44.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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. 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Beugels J DMJ, Van Der Hulst R, Kramer BW, Wolters ECH. Efficacy of different doses of human autologous adult bone marrow stem cell transplantation on angiogenesis in an immune deficient rat model with hind limb ischemia. J Stem Cells Res Dev Ther. 2019. https://doi.org/10.24966/SRDT-2060/S1002 Beugels J DMJ, Van Der Hulst R, Kramer BW, Wolters ECH. Efficacy of different doses of human autologous adult bone marrow stem cell transplantation on angiogenesis in an immune deficient rat model with hind limb ischemia. J Stem Cells Res Dev Ther. 2019. https://​doi.​org/​10.​24966/​SRDT-2060/​S1002
54.
go back to reference 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 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.
go back to reference 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. 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Magenta A, Florio MC, Ruggeri M, Furgiuele S. Autologous cell therapy in diabetes‑associated critical limb ischemia: from basic studies to clinical outcomes (Review). Int J Mol Med 2021;48(3):173. https://doi.org/10.3892/ijmm.2021.5006. Epub 2021 Jul 19. PMID: 34278463; PMCID: PMC8285046. Magenta A, Florio MC, Ruggeri M, Furgiuele S. Autologous cell therapy in diabetes‑associated critical limb ischemia: from basic studies to clinical outcomes (Review). Int J Mol Med 2021;48(3):173. https://​doi.​org/​10.​3892/​ijmm.​2021.​5006. Epub 2021 Jul 19. PMID: 34278463; PMCID: PMC8285046.
61.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Attanasio S, Snell J. Therapeutic angiogenesis in the management of critical limb ischemia: current concepts and review. Cardiol Rev. 2009;17:115–20.PubMedCrossRef 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.
go back to reference 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. 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.
go back to reference Tongers J, Roncalli JG, Losordo DW. Therapeutic angiogenesis for critical limb ischemia: microvascular therapies coming of age. Circulation. 2008;118:9–16.PubMedCrossRef Tongers J, Roncalli JG, Losordo DW. Therapeutic angiogenesis for critical limb ischemia: microvascular therapies coming of age. Circulation. 2008;118:9–16.PubMedCrossRef
79.
go back to reference Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: an update. Cell Transplant. 2016;25:829–48.PubMedCrossRef Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: an update. Cell Transplant. 2016;25:829–48.PubMedCrossRef
80.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Trounson A, McDonald C. Stem Cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17:11–22.PubMedCrossRef Trounson A, McDonald C. Stem Cell therapies in clinical trials: progress and challenges. Cell Stem Cell. 2015;17:11–22.PubMedCrossRef
84.
85.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Shmelkov SV, St Clair R, Lyden D, Rafii S. AC133/CD133/Prominin-1. Int J Biochem Cell Biol. 2005;37:715–9.PubMedCrossRef Shmelkov SV, St Clair R, Lyden D, Rafii S. AC133/CD133/Prominin-1. Int J Biochem Cell Biol. 2005;37:715–9.PubMedCrossRef
91.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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. 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.
go back to reference 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 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.
go back to reference Beare A, Stockinger H, Zola H, Nicholson I. Monoclonal antibodies to human cell surface antigens. Curr Protoc Immunol. 2008;Appendix 4:4A. Beare A, Stockinger H, Zola H, Nicholson I. Monoclonal antibodies to human cell surface antigens. Curr Protoc Immunol. 2008;Appendix 4:4A.
96.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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. 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.