Autologous peripheral blood mononuclear cells from selective filtration for treatment of chronic lower limb lesions: Results at 4 years

Submitted: October 13, 2020
Accepted: March 30, 2021
Published: July 30, 2021
Abstract Views: 334
PDF (Italiano): 205
PDF: 51
Appendix (Italiano): 0
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

A selective filtration technology has recently been introduced on the market to produce an autologous concentrate of Peripheral Blood Mononucleate Cells (PBMNC) with indication for use for human cell therapy. PBMNCs are indicated in the treatment of chronic lower limb injuries. The purpose of this study is to assess the efficacy and tolerability of this treatment in a group of patients who presented skin ulcers of the lower limbs, with various aetiology, not responders to traditional and advanced topical therapies. The study is prospective. Eight patients were treated with a total of 22 skin ulcers with variable etiology. Autologous PBMNCs were implanted along the course of the reference tibial arteries and in the peri-lesional area. All patients were subjected to a cycle of three infiltrations, performed in the operating room, on a monthly basis, except one patient who was subjected to a fourth implant, because the operator considered that a further one would accelerate the already regenerative state of the skin. Of the 22 ulcers treated with this method, 14 have reached complete recovery within a month of the end of the three implants, while 8 have gone towards a clear improvement. All patients showed good compliance to treatment and no minor or major adverse effects were reported. Fifty per cent of the treated patients were followed up four years after the end of treatment, and only one patient had a recurrent skin ulcer, but elsewhere from the initial one. The PBMNCs, produced with selective filtration system, have been shown to be an effective treatment of chronic lesions with different etiology of the lower limbs. The healing of all skin lesions treated quickly, the sharp reduction of pain, and the absence of recurrence at four years suggest a lasting clinical effect over time.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Agus GB, Allegra C, Arpaia G, et al. Linee guida. Collegio Italiano di Flebologia - Revisione 2013. Acta Phlebologica 2013;14.
Platsidaki E, Kouris A, Christodoulou C. Psychosocial aspects in patients with chronic leg ulcers. Wounds 2017;29:306-10. DOI: https://doi.org/10.25270/WNDS/2017.10.306310
Patel AS, Smith A, Nucera S, et al. TIE2-expressing monocytes/macrophages regulate revascularization of the ischemic limb. EMBO Mol Med 2013;5:858–69. DOI: https://doi.org/10.1002/emmm.201302752
Krishnasamy K, Limbourg A, Kapanadze T, et al. Blood vessel control of macrophage maturation promotes arteriogenesis in ischemia. Nat Commun 2017;8:952. DOI: https://doi.org/10.1038/s41467-017-00953-2
Van Weel V, Toes REM, Seghers L, et al. Natural killer cells and CD4+ T-cells modulate collateral artery development. Arterioscler Thromb Vasc Biol 2007;27:2310–8. DOI: https://doi.org/10.1161/ATVBAHA.107.151407
Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity 2016;44:450–62. DOI: https://doi.org/10.1016/j.immuni.2016.02.015
Larouche J, Sheoran S, Maruyama K, Martino MM. Immune regulation of skin wound healing: mechanisms and novel therapeutic targets. Adv Wound Care 2018;7:209–31. DOI: https://doi.org/10.1089/wound.2017.0761
Gurevich DB, Severn CE, Twomey C, et al. Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression. EMBO J 2018;37:e97786. DOI: https://doi.org/10.15252/embj.201797786
De Angelis B, Gentile P, Orlandi F, et al. Limb rescue: a new autologous-peripheral blood mononuclear cells technology in critical limb ischemia and chronic ulcers. Tissue Eng Part C Methods 2015;21:423–35. DOI: https://doi.org/10.1089/ten.tec.2014.0245
Persiani F, Paolini A, Camilli D, 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. DOI: https://doi.org/10.1016/j.avsg.2018.05.036
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. DOI: https://doi.org/10.1161/CIRCRESAHA.116.309045
Spaltro G, Straino S, Gambini E, et al. Characterization of the pall celeris system as a point-of-care device for therapeutic angiogenesis. Cytotherapy 2015;17:1302–13. DOI: https://doi.org/10.1016/j.jcyt.2015.04.006
Mariani F, Macciò A AM. Consensus conference on compression therapy. Airali; 2018: pp. 44–9.
Ogle ME, Segar CE, Sridhar S, Botchwey EA. Monocytes and macrophages in tissue repair: Implications for immunoregenerative biomaterial design. Exp Biol Med 2016;241:1084–97. DOI: https://doi.org/10.1177/1535370216650293
Krzyszczyk P, Schloss R, Palmer A, Berthiaume F. The role of macrophages in acute and chronic wound healing and interventions to promote pro-wound healing phenotypes. Front Physiol 2018;9:419. DOI: https://doi.org/10.3389/fphys.2018.00419
Rodero MP, Legrand JMD, Bou-Gharios G, Khosrotehrani K. Wound-associated macrophages control collagen 1α2 transcription during the early stages of skin wound healing. Exp Dermatol 2013;22:143-5. DOI: https://doi.org/10.1111/exd.12068
Do N, Willenborg S, Eming SA. Molecular mechanisms and functional consequences of blood monocyte recruitment and macrophage activation in tissue repair and fibrosis. Exp Dermatol 2015;24:20-2.
Willenborg S, Eming SA. Macrophages-sensors and effectors coordinating skin damage and repair. J German Soc Dermatol 2014;12:214–21. DOI: https://doi.org/10.1111/ddg.12290
Moore EM, Maestas, Jr. DR, Comeau HY, Elisseeff JH. The immune system and its contribution to variability in regenerative medicine. Tissue Eng Part B Rev 2020;ten.TEB.2019.0335.
Julier Z, Park AJ, Briquez PS, et al. Promoting tissue regeneration by modulating the immune system. Acta Biomater 2017;53:13–28. DOI: https://doi.org/10.1016/j.actbio.2017.01.056
Forbes SJ, Rosenthal N. Preparing the ground for tissue regeneration: From mechanism to therapy. Nat Med 2014;20:857–69. DOI: https://doi.org/10.1038/nm.3653
Ta Ploeger D, Hosper NA, Schipper M, et al. Cell plasticity in wound healing: paracrine factors of M1/ M2 polarized macrophages influence the phenotypical state of dermal fibroblasts. Cell Comm Signaling 2013;11:29. DOI: https://doi.org/10.1186/1478-811X-11-29
Anghelina M, Krishnan P, Moldovan L, Moldovan NI. Monocytes/macrophages cooperate with progenitor cells during neovascularization and tissue repair: Conversion of cell columns into fibrovascular bundles. Am J Pathol 2006;168:529–41. DOI: https://doi.org/10.2353/ajpath.2006.050255
Naik S, Larsen SB, Cowley CJ, Fuchs E. Leading edge two to tango: dialog between immunity and stem cells in health and disease. Cell 2018;175:908–20. DOI: https://doi.org/10.1016/j.cell.2018.08.071
Sharma A, Rudra D. Emerging functions of regulatory t cells in tissue homeostasis. Front Immunol 2018;9:883. DOI: https://doi.org/10.3389/fimmu.2018.00883
Li J, Tan J, Martino MM, Lui KO. Regulatory T-cells: Potential regulator of tissue repair and regeneration. Front Immunol 2018;9:585. DOI: https://doi.org/10.3389/fimmu.2018.00585
Torres-Castro I, Arroyo-Camarena àšD, Martìnez-Reyes CP, et al. Human monocytes and macrophages undergo M1-type inflammatory polarization in response to high levels of glucose. Immunol Lett 2016;176:81–9. DOI: https://doi.org/10.1016/j.imlet.2016.06.001
Di Pardo A, Cappello E, Pepe G, et al. Infusion of autologous-peripheral blood mononuclear cells : a new approach for limb salvage in patients with diabetes. In: 7th International Diabetic Foot Congress abu Dhabi. IFD Congress Abu Dhabi 4-8 December 2017.
Arnold L, Henry A, Poron F, et al. Infl ammatory monocytes recruited after skeletal muscle injury switch into antiinfl ammatory macrophages to support myogenesis. J Exp Med 2007;204:1057–69. DOI: https://doi.org/10.1084/jem.20070075
Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm. Nat Immunol 2010;11:889-96. DOI: https://doi.org/10.1038/ni.1937
Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 2011;11:723–737. DOI: https://doi.org/10.1038/nri3073
Kimball A, Schaller M, Joshi A, et al. Ly6C Hi blood monocyte/macrophage drive chronic inflammation and impair wound healing in diabetes mellitus. Arterioscler Thromb Vasc Biol 2018;38:1102–14. DOI: https://doi.org/10.1161/ATVBAHA.118.310703
Liang C, Yang KY, Chan VW, et al. CD8+ T-cell plasticity regulates vascular regeneration in type-2 diabetes. Theranostics 2020;10:4217–32. DOI: https://doi.org/10.7150/thno.40663
Kwee BJ, Seo BR, Najibi AJ, et al. Treating ischemia via recruitment of antigen-specific T cells. Sci Adv 2019;5:eaav6313. DOI: https://doi.org/10.1126/sciadv.aav6313
Leung OM, Li J, Li X, et al. Regulatory T cells promote apelin-mediated sprouting angiogenesis in type 2 diabetes. Cell Rep 2018;24:1610–26. DOI: https://doi.org/10.1016/j.celrep.2018.07.019
Churdchomjan W, Kheolamai P, Manochantr S, et al. Comparison of endothelial progenitor cell function in type 2 diabetes with good and poor glycemic control. BMC Endocr Disord 2010;10:5. DOI: https://doi.org/10.1186/1472-6823-10-5
Dopheide JF, Geissler P, Rubrech J, et al. Inflammation is associated with a reduced number of pro-angiogenic Tie-2 monocytes and endothelial progenitor cells in patients with critical limb ischemia. Angiogenesis 2016;19:67–78. DOI: https://doi.org/10.1007/s10456-015-9489-y
Caravaggi CMF, Panunzi Andrea, Sangalli E SG. Clinical outcome of autologous PB-MNC in treatment of non infected ischemic DFU (3C TUC) in non option CLI. In: 6th World Union of Wound Healing Societes; 2020.
Scatena A, Maioli F PP, Ventoruzzo G LF, et al. Does autologous peripheral mononuclear cells implant allow foot surgery in diabetic patients with critical limb ischaemia not eligible for revascularization? In: 8th International Symposium Diabetic Foot. The Hague- Netherlands; 2019: p. 95.
Colonna MR, Flavia L, Gabriele D, et al. Regenerative approaches regenerative in wound healing : new new alternatives for older tools. In: Alexandrescu V (ed). Wound Healing- New Insight into Ancient Challenges. IntechOpen; 2016: pp. 155–63. DOI: https://doi.org/10.5772/64133
Palermo C, Sanfiorenzo A, Trigona C, Bernardini G. Role of monocytes in the treatment of chronic limb ischemia and "hard to heal" ulcers. J Vasc Surg 2018;68:e119. DOI: https://doi.org/10.1016/j.jvs.2018.08.026
Benoit E, O'donnell TF, Patel AN. Safety and efficacy of autologous cell therapy in critical limb ischemia: a systematic review. Cell Transplant 2013;22:545–62. DOI: https://doi.org/10.3727/096368912X636777
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. DOI: https://doi.org/10.1186/s13287-019-1254-5
DubskའM, JirkovskࡠA, Bem R, et al. Cell therapy of critical limb ischemia in diabetic patients – State of art. Diabetes Res Clin Pract 2017;126:263–71. DOI: https://doi.org/10.1016/j.diabres.2017.02.028

How to Cite

Bucalossi, M., & Mariani, F. (2021). Autologous peripheral blood mononuclear cells from selective filtration for treatment of chronic lower limb lesions: Results at 4 years. Italian Journal of Wound Care, 5(2). https://doi.org/10.4081/ijwc.2021.69