Endothelial colony forming cells (or ECFCs) are adult endothelial progenitor cells capable of differentiating to regenerate endothelial cell populations. They are residents of adult vasculature and are also thought to migrate to areas of injury as one form of circulating endothelial cell. They are thought to play a critical role in vascular healing after injury as well as developmental angiogenesis.
ECFCs are commercially available and phenotypically identified by the positive markers CD34, CD31, VEGFR2, eNOS, CD105, and vWF. They also must test negative for CD133, CD45, and CD117. ECFCs are named for their ability to form colonies of cells which progress rapidly to capillary-like networks in vitro when cultured in biopolymer matrix, and in vivo.
A hierarchy has been demonstrated to exist within ECFC populations with regard to proliferative potential. Certain cells within the heterogeneous group of colony forming cells are demonstrated to reach significantly higher population doublings, and retain high levels of telomerase activity. These have been termed high proliferative potential endothelial colony forming cells, or HPP-ECFCs. In contrast, other cells that fit the phenotypic profile for an ECFC but do not maintain the same level of activity are LPP-ECFCs.
Vascular endothelial stem cells have been defined as rare endothelial colony forming cells with extremely high proliferative potential. They have been identified by marker analysis as lin- (lineage negative) CD31+, CD105+, Sca-1+, CD117 (ckit)+ and thought have the ability to generate functional vasculature from single cells.
ECFCs have been shown to decline in number and clonal ability with age or peripheral arterial disease, though are increased with acute myocardial infarction. A low number of ECFCs has been identified as a risk factor for infant diseases such as bronchopulmonary dysplasia. ECFCs can become dysfunctional in gestational diabetes (rescued by Vitamin D administration), smoking (driven by DNA damage), and premature birth (driven by decreased expression of histone deacetylase SIRT1). ECFCs are thus thought to have a large potential in therapies for vasculopathies of various etiologies.
ECFC-like cells have also been generated from pluripotent stem cells, perhaps eliminating the need for direct harvesting of the cells for future use.
- Mund JA, Estes ML, Yoder MC, Ingram DA, Case J (2012). "Flow cytometric identification and functional characterization of immature and mature circulating endothelial cells". Arterioscler. Thromb. Vasc. Biol. 32 (4): 1045–53. doi:10.1161/ATVBAHA.111.244210. PMC 3306529. PMID 22282356.
- Hyslop P, Grove I, Ingram D, Yoder M (2009). "Poietics ECFCs–Clonal Human Endothelial Colony Forming Cells : A New Highly Characterized Research Reagent to Study the Formation of Emergent Vascular Structures Both In Vitro and In Vivo". Lonza Resource Notes: 3–5.
- Hur J, Yoon CH, Kim HS, Choi JH, Kang HJ, Hwang KK, Oh BH, Lee MM, Park YB (2004). "Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis". Arterioscler. Thromb. Vasc. Biol. 24 (2): 288–93. doi:10.1161/01.ATV.0000114236.77009.06. PMID 14699017.
- Ingram DA, Mead LE, Tanaka H, Meade V, Fenoglio A, Mortell K, Pollok K, Ferkowicz MJ, Gilley D, Yoder MC (2004). "Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood". Blood. 104 (9): 2752–60. doi:10.1182/blood-2004-04-1396. PMID 15226175.
- Sedwick C (2012). "On the hunt for vascular endothelial stem cells". PLOS Biol. 10 (10): e1001408. doi:10.1371/journal.pbio.1001408. PMC 3472991. PMID 23091421.
- Fang S, Wei J, Pentinmikko N, Leinonen H, Salven P (2012). "Generation of functional blood vessels from a single c-kit+ adult vascular endothelial stem cell". PLOS Biol. 10 (10): e1001407. doi:10.1371/journal.pbio.1001407. PMC 3473016. PMID 23091420.
- Shelley WC, Leapley AC, Huang L, Critser PJ, Zeng P, Prater D, Ingram DA, Tarantal AF, Yoder MC (2012). "Changes in the frequency and in vivo vessel-forming ability of rhesus monkey circulating endothelial colony-forming cells across the lifespan (birth to aged)". Pediatr. Res. 71 (2): 156–61. doi:10.1038/pr.2011.22. PMC 3358134. PMID 22258126.
- Baker CD, Balasubramaniam V, Mourani PM, Sontag MK, Black CP, Ryan SL, Abman SH (2012). "Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia". Eur. Respir. J. 40 (6): 1516–22. doi:10.1183/09031936.00017312. PMC 5596882. PMID 22496315.
- Gui J, Rohrbach A, Borns K, Hillemanns P, Feng L, Hubel CA, von Versen-Höynck F (2015). "Vitamin D rescues dysfunction of fetal endothelial colony forming cells from individuals with gestational diabetes". Placenta. 36 (4): 410–8. doi:10.1016/j.placenta.2015.01.195. PMID 25684656.
- Paschalaki KE, Starke RD, Hu Y, Mercado N, Margariti A, Gorgoulis VG, Randi AM, Barnes PJ (2013). "Dysfunction of endothelial progenitor cells from smokers and chronic obstructive pulmonary disease patients due to increased DNA damage and senescence". Stem Cells. 31 (12): 2813–26. doi:10.1002/stem.1488. PMC 4377082. PMID 23897750.
- Vassallo PF, Simoncini S, Ligi I, Chateau AL, Bachelier R, Robert S, Morere J, Fernandez S, Guillet B, Marcelli M, Tellier E, Pascal A, Simeoni U, Anfosso F, Magdinier F, Dignat-George F, Sabatier F (2014). "Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression". Blood. 123 (13): 2116–26. doi:10.1182/blood-2013-02-484956. PMID 24518759.
- Prasain N, Lee MR, Vemula S, Meador JL, Yoshimoto M, Ferkowicz MJ, Fett A, Gupta M, Rapp BM, Saadatzadeh MR, Ginsberg M, Elemento O, Lee Y, Voytik-Harbin SL, Chung HM, Hong KS, Reid E, O'Neill CL, Medina RJ, Stitt AW, Murphy MP, Rafii S, Broxmeyer HE, Yoder MC (2014). "Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells". Nat. Biotechnol. 32 (11): 1151–7. doi:10.1038/nbt.3048. PMC 4318247. PMID 25306246.