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Pro-angiogenic induction of myeloid cells for therapeutic angiogenesis can induce mitogen-activated protein kinase p38-dependent foam cell formation. | LitMetric

AI Article Synopsis

  • Clinical trials using hematopoietic cells, endothelial progenitor cells (EPC), and mesenchymal stromal cells (MSC) for vascular regeneration raise concerns about these cells possibly contributing to atherosclerosis through foam cell formation.
  • The study found that only monocytes formed foam cells after pro-angiogenic induction, while EPC and MSC did not accumulate lipid droplets, suggesting they are safer for vascular regeneration.
  • The research highlights the importance of understanding cell biology to create more effective therapeutic strategies that combine the benefits of vascular regeneration with the prevention of atherosclerosis.

Article Abstract

Background Aims: Clinical trials for therapeutic angiogenesis use blood- or bone marrow-derived hematopoietic cells, endothelial progenitor cells (EPC) and mesenchymal stromal cells (MSC) for vascular regeneration. Recently concerns have emerged that all three cell types could also contribute to atherosclerosis by foam cell formation. Therefore, we asked whether human myelomonocytic cells, EPC or MSC can accumulate lipid droplets (LD) and develop into foam cells.

Methods: LD accumulation was quantified by flow cytometry, confocal microscopy and cholesterol measurement in each of the cell types. The impact of an initial pro-angiogenic induction on subsequent foam cell formation was studied to mimic relevant settings already used in clinical trials. The phosphorylation state of intracellular signaling molecules in response to the pro-angiogenic stimulation was determined to delineate the operative mechanisms and establish a basis for interventional strategies.

Results: Foam cells were formed by monocytes but not by EPC or MSC after pro-angiogenic induction. Mitogen-activated protein kinase (MAPK) p38 phosphorylation was enhanced and kinase inhibition almost abrogated intracellular LD accumulation in monocytes.

Conclusions: These data suggest that hematopoietic cell preparations containing monocytes bear the risk of foam cell formation after pro-angiogenic induction. Instead, EPC and MSC may drive vascular regeneration without atherogenesis aggravation. A thorough understanding of cell biology is necessary to develop new strategies combining pro-angiogenic and anti-atherogenic effects during cell therapy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173858PMC
http://dx.doi.org/10.3109/14653249.2010.536214DOI Listing

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