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Review
. 2022 May 4;12(5):1137.
doi: 10.3390/diagnostics12051137.

PBMNCs Treatment in Critical Limb Ischemia and Candidate Biomarkers of Efficacy

Matilde Zamboni  1 , Massimo Pedriali  2 , Luca Ferretto  1 , Sabrina Scian  3 , Francesca Ghirardini  1 , Riccardo Bozza  1 , Romeo Martini  1 , Sandro Irsara  1
Affiliations
Review

PBMNCs Treatment in Critical Limb Ischemia and Candidate Biomarkers of Efficacy

Matilde Zamboni et al. Diagnostics (Basel). .

Abstract

When in critical limb ischemia (CLI) the healing process aborts or does not follow an orderly and timely sequence, a chronic vascular wound develops. The latter is major problem today, as their epidemiology is continuously increasing due to the aging population and a growth in the incidence of the underlying diseases. In the US, the mean annualized prevalence of necrotic wounds due to the fact of CLI is 1.33% (95% CI, 1.32-1.34%), and the cost of dressings alone has been estimated at USD 5 billion per year from healthcare budgets. A promising cell treatment in wound healing is the local injection of peripheral blood mononuclear cells (PBMNCs). The treatment is aimed to induce angiogenesis as well to switch inflammatory macrophages, called the M1 phenotype, into anti-inflammatory macrophages, called M2, a phenotype devoted to tissue repair. This mechanism is called polarization and is a critical step for the healing of all human tissues. Regarding the clinical efficacy of PBMNCs, the level of evidence is still low, and a considerable effort is necessary for completing the translational process toward the patient bed site. From this point of view, it is crucial to identify some candidate biomarkers to detect the switching process from M1 to M2 in response to the cell treatment.

Keywords: biomarkers; critical limb ischemia; macrophages; peripheral blood mononuclear cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Macrophage gene expression during the classically activated M1 and alternatively activated M2 phenotypes: (a) genes up and down regulation during M1 activation; (b) genes up and down regulation during M2 activation.
Figure 2
Figure 2
Genes expressed during M1 and M2 macrophages activation.
Figure 3
Figure 3
Bioptic human tissue after treatment with PBMNCs: (a) hematoxylin and eosin—granulation tissue permeated by chronic inflammation with a rich granulocyte and macrophage population; (b) immunohistochemistry (IHC)—CD68 is a pan macrophage marker (M0 + M1 + M2); (c) IHC—C-Myc marks the M2 subpopulation in vivo.
See this image and copyright information in PMC

References

    1. Shu J., Santulli G. Update on peripheral artery disease: Epidemiology and evidence-based facts. Atherosclerosis. 2018;275:379–381. doi: 10.1016/j.atherosclerosis.2018.05.033. - DOI - PMC - PubMed
    1. Fontaine R., Kim M., Kieny R. Surgical Treatment of Peripheral Circulation Disorders. Helv. Chir. Acta. 1954;21:499–533. - PubMed
    1. Rutherford R.B., Baker J.D., Ernst C., Johnston K.W., Porter J.M., Ahn S., Jones D.N. Recommended standards for reports dealing with lower extremity ischemia: Revised version. J. Vasc. Surg. 1997;26:517–538. doi: 10.1016/S0741-5214(97)70045-4. - DOI - PubMed
    1. Fowkes F.G., Rudan D., Rudan I., Aboyans V., Denenberg J.O., McDermott M.M., Norman P.E., Sampson U.K.A., Williams L.J., Mensah G.A., et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: A systematic review and analysis. Lancet. 2013;382:1329–1340. doi: 10.1016/S0140-6736(13)61249-0. - DOI - PubMed
    1. Nehler M.R., Duval S., Diao L., Annex B.H., Hiatt W.R., Rogers K., Zakharyan A., Hirsch A.T. Epidemiology of peripheral arterial disease and critical limb ischemia in an insured national population. J. Vasc. Surg. 2014;60:686–695. doi: 10.1016/j.jvs.2014.03.290. - DOI - PubMed