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The Onset of Intussusceptive Angiogenesis in COVID-19 Patients Might Come from the Mobilization of Stem Cell Sub-Populations Expressing the Hemangioblast Marker CD143

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Abstract

COVID-19 and infectious diseases have been included in strategic development goals (SDG) of United Nations (UN). The SARS-CoV-2 pandemic has unveiled complex pathophysiological mechanisms underpinning COVID-19, notably inducing a systemic acquired vascular hemopathy characterized by endothelial dysfunction and intussusceptive angiogenesis, a rapid vascular remodeling process identified as a hallmark in severe COVID-19 cases affecting pulmonary and cardiac tissues. Stem cell migration have been proposed as significant regulators of this neoangiogenic process. In a monocentric cross-sectional study, through spectral flow cytometry analysis of peripheral blood mononuclear cells, we identified a distinct stem cell subpopulation mobilized in critical COVID-19. Indeed, by an unsupervised analysis generating a UMAP representation we highlighted eleven different clusters in critical and non-critical COVID-19 patients. Only one cluster was significantly associated to critical COVID-19 compared to non-critical patients. This cluster expressed the markers: CD45dim, CD34+, CD117+, CD147+, and CD143+, and were negative for CD133. Higher level of expression of hemangioblast markers CD143 were found in critical COVID-19 patients. This population, indicative of hemangioblast-like cells, suggests a key role in COVID-19-related neoangiogenesis, potentially driving the severe vascular complications observed. Our findings underscore the need for further investigation into the contributions of adult stem cells in COVID-19 pathology, offering new insights into therapeutic targets and interventions.

Graphical Abstract

A significant mobilization of Lin−CD34+CD143+in peripheral blood is observed in critical COVID-19 and could participate in intussusceptive angiogenesis observed in lungs in COVID-19. Graphical abstract: Using a flow cytometry approach and an unsupervised analysis, we demonstrated in critical COVID-19 a significant mobilization of Lin−CD34+CD143+ in peripheral blood. This cell population could be at the origin of newly formed endothelial cells participating in intussusceptive angiogenesis observed in lungs

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Fig. 1

Data Availability

Raw data are available upon request.

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Funding

This work was funded with grants from the French national agency for research ANR SARCODO (Fondation de France) and Mécénat Covid AP-HP.

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Authors and Affiliations

  1. Université Paris-Cité, Innovative Therapies in Hemostasis, INSERM, Paris, F-75006, France

    Lou Soret, Coralie L. Guerin, Jean-Luc Diehl, Aurélien Philippe, Pascale Gaussem & David M. Smadja

  2. Hematology Department, AP-HP, Saint louis Hospital, Paris, F-75010, France

    Lou Soret

  3. Cytometry Platform, Curie CoreTech, Institut Curie, Paris, F-75005, France

    Coralie L. Guerin & Léa Guyonnet

  4. Université Paris-Cité, PARCC, INSERM, Paris, F-75015, France

    Guillaume Goudot

  5. Vascular medicine Department, AP-HP, Georges Pompidou European Hospital, Paris, F-75015, France

    Guillaume Goudot

  6. Intensive Care Department, AP-HP, Georges Pompidou European Hospital, Paris, F-75015, France

    Jean-Luc Diehl

  7. Hematology Department, AP-HP, Georges Pompidou European Hospital, Paris, F-75015, France

    Aurélien Philippe, Pascale Gaussem & David M. Smadja

  8. Innovative Therapies in Hemostasis, Hematology Department in Georges Pompidou, Paris-Cité University, INSERM, European Hospital, 20 rue Leblanc, 75015, Paris, France

    David M. Smadja

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  1. Lou Soret
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  2. Coralie L. Guerin
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  3. Guillaume Goudot
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  4. Léa Guyonnet
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  6. Aurélien Philippe
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  7. Pascale Gaussem
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  8. David M. Smadja
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Contributions

CG and DMS designed the study. CLG, LS, and LG performed the experiments and analyzed data. LS, CLG, JLD, PG and DMS interpreted and discussed results and wrote the paper. GG and JLD included patients in SARCODO. Authors declare that the submitted work is original and has not been published before and that the work is not under consideration for publication elsewhere.

Corresponding author

Correspondence to David M. Smadja.

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Ethical Approval

The studies involving human participants were reviewed and approved by Comité de protection des personnes Sud Ouest et Outre Mer IV. The patients/participants provided their written informed consent to participate in this study. The study was performed in accordance with the Declaration of Helsinki and a written consent form was signed by all patients included or their trusted relatives at the time of enrollment (SARCODO study; A0104831A; NCT04624997).

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Soret, L., Guerin, C.L., Goudot, G. et al. The Onset of Intussusceptive Angiogenesis in COVID-19 Patients Might Come from the Mobilization of Stem Cell Sub-Populations Expressing the Hemangioblast Marker CD143. Stem Cell Rev and Rep (2024). https://doi.org/10.1007/s12015-024-10727-1

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  • DOI: https://doi.org/10.1007/s12015-024-10727-1

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