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Interleukin 1β: A New Target to Improve Vascular Repair by Myeloid Angiogenic Cells?

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Review of “The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes through the Induction of IL1β” from STEM CELLS by Stuart P. Atkinson

Myeloid angiogenic cells (MACs) isolated from the peripheral blood [1, 2] release a potent mixture of paracrine acting angiogenic factors and display great promise for a wide range of diseases and disorders, such as diabetes-associated tissue ischemia. However, diabetes can affect MAC-based vascular repair [3], due to a proposed pro-angiogenic to anti-angiogenic switch [4], thereby limiting autologous applications.

Researchers from the laboratory of Reinhold J. Medina (Queen's University Belfast, UK) aimed to delineate the molecular mechanisms controlling MAC dysfunction under diabetic conditions, and their new STEM CELLS study now suggests that diabetes induces an M2 to M1 phenotypic shift, a reduction in pro-angiogenic capacities, and an Interleukin 1β (IL1β)-driven loss of vascular repair abilities in MACs [5].

Chambers et al. compared healthy human peripheral blood MACs with those cultured in high-glucose conditions to mimic the diabetic effects of hyperglycemia. Analysis of MACs suggested that they shared some M2 macrophage proangiogenic characteristics, but additionally expressed high levels of the CD163 cell surface marker, a scavenger receptor involved in the clearance of hemoglobin. 

Interestingly, high-glucose-treated MACs displayed reduced proangiogenic capabilities during in vitro 3D Matrigel tubulogenesis assays, which the authors linked to a significant increase in the expression of the Interleukin-(IL)1β inflammatory cytokine and a shift towards an M1-like MAC fate. However, treatment with an IL1β neutralizing antibody abrogated high-glucose-induced antiangiogenic effects.

Moving in vivo, the study confirmed that MACs isolated from type-1 diabetes patients with microvascular complications also upregulated IL1β compared to patients without microvascular complications or nondiabetic volunteers, suggesting that IL1β suppression may represent an exciting target to promote MAC-mediated vascular repair. 

The authors now hope that their results will provide the means to restore MAC functionality in human diabetic patients and promote vascular repair - to see if this approach is successful, stay tuned to the Stem Cells Portal.

References

  1. Medina RJ, O'Neill CL, Sweeney M, et al., Molecular analysis of endothelial progenitor cell (EPC) subtypes reveals two distinct cell populations with different identities. BMC Medical Genomics 2010;3:18.
  2. Medina RJ, O'Neill CL, O'Doherty TM, et al., Myeloid angiogenic cells act as alternative M2 macrophages and modulate angiogenesis through interleukin-8. Mol Med 2011;17:1045-55.
  3. Caballero S, Sengupta N, Afzal A, et al., Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells. Diabetes 2007;56:960-967.
  4. Awad O, Jiao C, Ma N, et al., Obese Diabetic Mouse Environment Differentially Affects Primitive and Monocytic Endothelial Cell Progenitors. STEM CELLS 2005;23:575-583.
  5. Chambers SEJ, O'Neill CL, Guduric‐Fuchs J, et al., The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes Through the Induction of IL1β. STEM CELLS 2018;36:834-843.