Do Endothelial Colony‐forming Cells Come From Bone Marrow or Vessels/VSELs?

This is a preview of subscription content, access via your institution.


  1. 1.

    Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., et al. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275(5302), 964–967.

    CAS  Article  Google Scholar 

  2. 2.

    Smadja, D. M., Melero-Martin, J. M., Eikenboom, J., Bowman, M., Sabatier, F., & Randi, A. M. (2019). Standardization of methods to quantify and culture endothelial colony-forming cells derived from peripheral blood: Position paper from the International Society on Thrombosis and Haemostasis SSC. Journal of Thrombosis and Haemostasis, 17(7), 1190–1194.

    Article  Google Scholar 

  3. 3.

    Fujisawa, T., Tura-Ceide, O., Hunter, A., Mitchell, A., Vesey, A., Medine, C., et al. (2019). Endothelial progenitor cells do not originate from the bone marrow. Circulation, 140(18), 1524–1526.

    CAS  Article  Google Scholar 

  4. 4.

    Lin, Y., Weisdorf, D. J., Solovey, A., & Hebbel, R. P. (2000). Origins of circulating endothelial cells and endothelial outgrowth from blood. The Journal of Clinical Investigation, 105(1), 71–77.

    CAS  Article  Google Scholar 

  5. 5.

    Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418(6893), 41–49.

    CAS  Article  Google Scholar 

  6. 6.

    Beltrami, A. P., Cesselli, D., Bergamin, N., Marcon, P., Rigo, S., Puppato, E., et al. (2007). Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow). Blood, 110(9), 3438–3446.

    CAS  Article  Google Scholar 

  7. 7.

    Kogler, G., Sensken, S., Airey, J. A., Trapp, T., Muschen, M., Feldhahn, N., et al. (2004). A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. The Journal of Experimental Medicine, 200(2), 123–135.

    Article  Google Scholar 

  8. 8.

    D’Ippolito, G., Diabira, S., Howard, G. A., Menei, P., Roos, B. A., & Schiller, P. C. (2004). Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. Journal of Cell Science, 117(Pt 14), 2971–2981.

    Article  Google Scholar 

  9. 9.

    Kuroda, Y., Kitada, M., Wakao, S., Nishikawa, K., Tanimura, Y., Makinoshima, H., et al. (2010). Unique multipotent cells in adult human mesenchymal cell populations. Proceedings of the National Academy of Sciences of the United States of America, 107(19), 8639–8643.

    CAS  Article  Google Scholar 

  10. 10.

    Shaikh, A., Anand, S., Kapoor, S., Ganguly, R., & Bhartiya, D. (2017). Mouse bone marrow VSELs exhibit differentiation into three embryonic germ lineages and germ & hematopoietic cells in culture. Stem Cell Reviews and Reports, 13(2), 202–216.

    CAS  Article  Google Scholar 

  11. 11.

    Ratajczak, M. Z., Ratajczak, J., Suszynska, M., Miller, D. M., Kucia, M., & Shin, D. M. (2017). A novel view of the adult stem cell compartment from the perspective of a quiescent population of very small embryonic-like stem cells. Circulation Research, 120(1), 166–178.

    CAS  Article  Google Scholar 

  12. 12.

    Guerin, C. L., Blandinieres, A., Planquette, B., Silvestre, J. S., Israel-Biet, D., Sanchez, O., et al. (2017). Very small embryonic-like stem cells are mobilized in human peripheral blood during hypoxemic COPD exacerbations and pulmonary hypertension. Stem Cell Reviews, 13(4), 561–566.

    CAS  Article  Google Scholar 

  13. 13.

    Havens, A. M., Sun, H., Shiozawa, Y., Jung, Y., Wang, J., Mishra, A., et al. (2014). Human and murine very small embryonic-like cells represent multipotent tissue progenitors, in vitro and in vivo. Stem Cells and Development, 23(7), 689–701.

    Article  Google Scholar 

  14. 14.

    Wu, J. H., Wang, H. J., Tan, Y. Z., & Li, Z. H. (2012). Characterization of rat very small embryonic-like stem cells and cardiac repair after cell transplantation for myocardial infarction. Stem Cells and Development, 21(8), 1367–1379.

    CAS  Article  Google Scholar 

  15. 15.

    Zhang, S., Zhao, L., Wang, J., Chen, N., Yan, J., & Pan, X. (2017). HIF-2alpha and Oct4 have synergistic effects on survival and myocardial repair of very small embryonic-like mesenchymal stem cells in infarcted hearts. Cell Death & Disease, 8(1), e2548.

    Article  Google Scholar 

  16. 16.

    Guerin, C. L., Loyer, X., Vilar, J., Cras, A., Mirault, T., Gaussem, P., et al. (2015). Bone-marrow-derived very small embryonic-like stem cells in patients with critical leg ischaemia: evidence of vasculogenic potential. Thrombosis and Haemostasis, 113(5), 1084–1094.

    Article  Google Scholar 

  17. 17.

    Li, Z., Solomonidis, E. G., Meloni, M., Taylor, R. S., Duffin, R., Dobie, R., et al. (2019). Single-cell transcriptome analyses reveal novel targets modulating cardiac neovascularization by resident endothelial cells following myocardial infarction. European Heart Journal, 40(30), 2507–2520.

    CAS  Article  Google Scholar 

  18. 18.

    El-Helw, M., Chelvarajan, L., Abo-Aly, M., Soliman, M., Milburn, G., Conger, A. L., et al. (2020). Identification of human Very Small Embryonic like Stem Cells (VSELS) in human heart tissue among young and old individuals. Stem Cell Reviews and Reports, 16(1), 181–185.

    CAS  Article  Google Scholar 

  19. 19.

    Kim, Y., Jeong, J., Kang, H., Lim, J., Heo, J., Ratajczak, J., et al. (2014). The molecular nature of very small embryonic-like stem cells in adult tissues. International Journal of Stem Cells , 7(2), 55–62.

    Article  Google Scholar 

  20. 20.

    Huber, T. L., Kouskoff, V., Fehling, H. J., Palis, J., & Keller, G. (2004). Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature, 432(7017), 625–630.

    CAS  Article  Google Scholar 

  21. 21.

    Oberlin, E., El Hafny, B., Petit-Cocault, L., & Souyri, M. (2010). Definitive human and mouse hematopoiesis originates from the embryonic endothelium: a new class of HSCs based on VE-cadherin expression. The International Journal of Developmental Biology, 54(6–7), 1165–1173.

    CAS  Article  Google Scholar 

  22. 22.

    Guerin, C. L., Guyonnet, L., Goudot, G., Revets, D., Konstantinou, M., Chipont, A., et al. (2020). Multidimensional proteomic approach of endothelial progenitors demonstrate expression of KDR restricted to CD19 cells. Stem Cell Reviews and Reports, 1–13.

  23. 23.

    Zambidis, E. T., Park, T. S., Yu, W., Tam, A., Levine, M., Yuan, X., et al. (2008). Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells. Blood, 112(9), 3601–3614.

    CAS  Article  Google Scholar 

  24. 24.

    Nevo, N., Lecourt, S., Bieche, I., Kucia, M., Cras, A., Blandinieres, A., et al. (2020). Valproic acid decreases endothelial colony forming cells differentiation and induces endothelial-to-mesenchymal transition-like process. Stem Cell Reviews and Reports, 16(2), 357–368.

    CAS  Article  Google Scholar 

  25. 25.

    Smadja, D. M., Dorfmuller, P., Guerin, C. L., Bieche, I., Badoual, C., Boscolo, E., et al. (2014). Cooperation between human fibrocytes and endothelial colony-forming cells increases angiogenesis via the CXCR4 pathway. Thrombosis and Haemostasis, 112(5), 1002–1013.

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Smadja, D. M. (2019). Vasculogenic stem and progenitor cells in human: future cell therapy product or liquid biopsy for vascular disease. Advances in Experimental Medicine and Biology, 1201, 215–237.

    CAS  Article  Google Scholar 

  27. 27.

    Smadja, D. M., d’Audigier, C., Guerin, C. L., Mauge, L., Dizier, B., Silvestre, J. S., et al. (2012). Angiogenic potential of BM MSCs derived from patients with critical leg ischemia. Bone Marrow Transplant, 47(7), 997–1000.

    CAS  Article  Google Scholar 

  28. 28.

    Gendron, N., Rosa, M., Blandinieres, A., Sottejeau, Y., Rossi, E., Van Belle, E., et al. (2021). Human aortic valve interstitial cells display proangiogenic properties during calcific aortic valve disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 41(1), 415–429.

    CAS  PubMed  Google Scholar 

  29. 29.

    Peichev, M., Naiyer, A. J., Pereira, D., Zhu, Z., Lane, W. J., Williams, M., et al. (2000). Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood, 95(3), 952–958.

    CAS  Article  Google Scholar 

  30. 30.

    Silvestre, J. S., Smadja, D. M., & Levy, B. I. (2013). Postischemic revascularization: from cellular and molecular mechanisms to clinical applications. Physiological Reviews, 93(4), 1743–1802.

    CAS  Article  Google Scholar 

  31. 31.

    Smadja, D. M., Bieche, I., Uzan, G., Bompais, H., Muller, L., Boisson-Vidal, C., et al. (2005). PAR-1 activation on human late endothelial progenitor cells enhances angiogenesis in vitro with upregulation of the SDF-1/CXCR4 system. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(11), 2321–2327.

    CAS  Article  Google Scholar 

  32. 32.

    Bompais, H., Chagraoui, J., Canron, X., Crisan, M., Liu, X. H., Anjo, A., et al. (2004). Human endothelial cells derived from circulating progenitors display specific functional properties compared with mature vessel wall endothelial cells. Blood, 103(7), 2577–2584.

    CAS  Article  Google Scholar 

  33. 33.

    Rossi, E., Poirault-Chassac, S., Bieche, I., Chocron, R., Schnitzler, A., Lokajczyk, A., et al. (2019). Human endothelial colony forming cells express intracellular CD133 that modulates their vasculogenic properties. Stem Cell Reviews and Reports, 15(4), 590–600.

    CAS  Article  Google Scholar 

Download references


This work was supported by grants from the PROMEX STIFTUNG FUR DIE FORSCHUNG foundation that we deeply thank.

Author information




GD wrote the manuscript. CLG, NG and TM corrected proofs and partipated to stem cell project in the Smadja’s team. DMS supervised the work and wrote manuscript.

Corresponding author

Correspondence to David M. Smadja.

Ethics declarations

Conflict of Interest

Authors declare no conflict of interest related to this work.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Detriche, G., Guerin, C.L., Gendron, N. et al. Do Endothelial Colony‐forming Cells Come From Bone Marrow or Vessels/VSELs?. Stem Cell Rev and Rep (2021).

Download citation