Abstract
Purpose of Review
Vascular endothelial stem cell (VESC) and progenitor cell are emerging as local resident regulators of vascular endothelial repair and replacement in mammalian subjects. However, widely recognized and accepted standard measures of stem cell function have yet to be published and, thus, we summarize some recent evidence that VESCs demonstrate stem cell properties in the process of endothelial cell (EC) lineage emergence, repair, and regeneration.
Recent Findings
Some rare resident ECs have been identified that are quiescent and reside within blood vessels but are activated and proliferate in response to injury. Transcriptome analyses of these ECs at a single cell level are providing new insights into VESC identity, including tissue specific EC heterogeneity.
Summary
Blood vessels and circulating blood contain rare immature ECs that display stem cell potential. Continuous efforts to define their precise location, origin, surface marker, and molecular signatures would enhance current approaches for purification of cells that would enable us to build new vessels for regenerative medicine.
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References
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Aird WC. Endothelial cell heterogeneity. Cold Spring Harb Perspect Med. 2012;2(1):a006429. https://doi.org/10.1101/cshperspect.a006429.
Ingram DA, Mead LE, Moore DB, Woodard W, Fenoglio A, Yoder MC. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells. Blood. 2005;105(7):2783–6. https://doi.org/10.1182/blood-2004-08-3057.
Alvarez DF, Huang L, King JA, ElZarrad MK, Yoder MC, Stevens T. Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity. Am J Phys Lung Cell Mol Phys. 2008;294(3):L419–30. https://doi.org/10.1152/ajplung.00314.2007.
Schniedermann J, Rennecke M, Buttler K, Richter G, Stadtler AM, Norgall S, et al. Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels. BMC Cell Biol. 2010;11:50. https://doi.org/10.1186/1471-2121-11-50.
Naito H, Kidoya H, Sakimoto S, Wakabayashi T, Takakura N. Identification and characterization of a resident vascular stem/progenitor cell population in preexisting blood vessels. EMBO J. 2012;31(4):842–55. https://doi.org/10.1038/emboj.2011.465.
Fang S, Wei J, Pentinmikko N, Leinonen H, Salven P. Generation of functional blood vessels from a single c-kit+ adult vascular endothelial stem cell. PLoS Biol. 2012;10(10):e1001407. https://doi.org/10.1371/journal.pbio.1001407.
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–7.
•• Wakabayashi T, Naito H, Suehiro JI, Lin Y, Kawaji H, Iba T, et al. CD157 marks tissue-resident endothelial stem cells with homeostatic and regenerative properties. Cell Stem Cell. 2018;22(3):384–97 e6. https://doi.org/10.1016/j.stem.2018.01.010 Identifies CD157 as a marker of tissue-resident vascular endothelial stem cells in large arteries and veins of several mouse organs that are capable of clonal expansion and in vivo vessel formation.
•• McDonald AI, Shirali AS, Aragon R, Ma F, Hernandez G, Vaughn DA, et al. Endothelial regeneration of large vessels is a biphasic process driven by local cells with distinct proliferative capacities. Cell Stem Cell. 2018;23(2):210–25 e6. https://doi.org/10.1016/j.stem.2018.07.011 Demonstrates that endothelial regeneration of mouse aorta intima is driven by local resident endothelial cells with distinct proliferative capacities and that Atf3 is required for regeneration of the endothelial lining of large arteries.
• Patel J, Seppanen EJ, Rodero MP, Wong HY, Donovan P, Neufeld Z, et al. Functional definition of progenitors versus mature endothelial cells reveals key SoxF-dependent differentiation process. Circulation. 2017;135(8):786–805. https://doi.org/10.1161/CIRCULATIONAHA.116.024754 Demonstrates an endothelial hierarchy from an endovascular progenitor to a mature differentited endothelial cell and an essential role of the SoxF-dependent transcription factors.
Weissman IL. Stem cells: units of development, units of regeneration, and units in evolution. Cell. 2000;100(1):157–68.
Weissman IL, Anderson DJ, Gage F. Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol. 2001;17:387–403. https://doi.org/10.1146/annurev.cellbio.17.1.387.
Spradling A, Drummond-Barbosa D, Kai T. Stem cells find their niche. Nature. 2001;414(6859):98–104. https://doi.org/10.1038/35102160.
Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature. 2003;425(6961):962–7. https://doi.org/10.1038/nature02060.
•• Medina RJ, Barber CL, Sabatier F, Dignat-George F, Melero-Martin JM, Khosrotehrani K, et al. Endothelial progenitors: a consensus statement on nomenclature. Stem Cells Transl Med. 2017;6(5):1316–20. https://doi.org/10.1002/sctm.16-0360 Provides a consensus statement on nomenclature of endothelial progenitor cell and calls for precise terminology based on defining cellular phenotype and function.
• Yoder MC. Endothelial stem and progenitor cells (stem cells): (2017 Grover Conference Series). Pulm Circ. 2018;8(1):2045893217743950. https://doi.org/10.1177/2045893217743950 Comprehensive review of the existence of endothelial and progenitor cells in blood vessels.
Medina RJ, O’Neill CL, O’Doherty TM, Wilson SE, Stitt AW. Endothelial progenitors as tools to study vascular disease. Stem Cells Int. 2012;2012:346735. https://doi.org/10.1155/2012/346735.
Case J, Mead LE, Bessler WK, Prater D, White HA, Saadatzadeh MR, et al. Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp Hematol. 2007;35(7):1109–18. https://doi.org/10.1016/j.exphem.2007.04.002.
Wu X, Lensch MW, Wylie-Sears J, Daley GQ, Bischoff J. Hemogenic endothelial progenitor cells isolated from human umbilical cord blood. Stem Cells. 2007;25(11):2770–6. https://doi.org/10.1634/stemcells.2006-0783.
Yoder MC. Is endothelium the origin of endothelial progenitor cells? Arterioscler Thromb Vasc Biol. 2010;30(6):1094–103. https://doi.org/10.1161/ATVBAHA.109.191635.
Mund JA, Estes ML, Yoder MC, Ingram DA Jr, Case J. Flow cytometric identification and functional characterization of immature and mature circulating endothelial cells. Arterioscler Thromb Vasc Biol. 2012;32(4):1045–53. https://doi.org/10.1161/ATVBAHA.111.244210.
Basile DP, Yoder MC. Circulating and tissue resident endothelial progenitor cells. J Cell Physiol. 2014;229(1):10–6. https://doi.org/10.1002/jcp.24423.
Medina RJ, O’Neill CL, Humphreys MW, Gardiner TA, Stitt AW. Outgrowth endothelial cells: characterization and their potential for reversing ischemic retinopathy. Invest Ophthalmol Vis Sci. 2010;51(11):5906–13. https://doi.org/10.1167/iovs.09-4951.
Yoon CH, Hur J, Park KW, Kim JH, Lee CS, Oh IY, et al. Synergistic neovascularization by mixed transplantation of early endothelial progenitor cells and late outgrowth endothelial cells: the role of angiogenic cytokines and matrix metalloproteinases. Circulation. 2005;112(11):1618–27. https://doi.org/10.1161/CIRCULATIONAHA.104.503433.
Medina RJ, O’Neill CL, Sweeney M, Guduric-Fuchs J, Gardiner TA, Simpson DA, et al. Molecular analysis of endothelial progenitor cell (EPC) subtypes reveals two distinct cell populations with different identities. BMC Med Genet. 2010;3:18. https://doi.org/10.1186/1755-8794-3-18.
Asahara T, Kawamoto A, Masuda H. Concise review: circulating endothelial progenitor cells for vascular medicine. Stem Cells. 2011;29(11):1650–5. https://doi.org/10.1002/stem.745.
Mukai N, Akahori T, Komaki M, Li Q, Kanayasu-Toyoda T, Ishii-Watabe A, et al. A comparison of the tube forming potentials of early and late endothelial progenitor cells. Exp Cell Res. 2008;314(3):430–40. https://doi.org/10.1016/j.yexcr.2007.11.016.
Medina RJ, O’Neill CL, O’Doherty TM, Knott H, Guduric-Fuchs J, Gardiner TA, et al. Myeloid angiogenic cells act as alternative M2 macrophages and modulate angiogenesis through interleukin-8. Mol Med. 2011;17(9–10):1045–55. https://doi.org/10.2119/molmed.2011.00129.
Cheng CC, Chang SJ, Chueh YN, Huang TS, Huang PH, Cheng SM, et al. Distinct angiogenesis roles and surface markers of early and late endothelial progenitor cells revealed by functional group analyses. BMC Genomics. 2013;14:182. https://doi.org/10.1186/1471-2164-14-182.
Lin Y, Weisdorf DJ, Solovey A, Hebbel RP. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest. 2000;105(1):71–7. https://doi.org/10.1172/JCI8071.
Ingram DA, Mead LE, Tanaka H, Meade V, Fenoglio A, Mortell K, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood. 2004;104(9):2752–60. https://doi.org/10.1182/blood-2004-04-1396.
Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, Li F, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood. 2007;109(5):1801–9. https://doi.org/10.1182/blood-2006-08-043471.
Hirschi KK, Ingram DA, Yoder MC. Assessing identity, phenotype, and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2008;28(9):1584–95. https://doi.org/10.1161/ATVBAHA.107.155960.
•• Tasev D, Koolwijk P, van Hinsbergh VW. Therapeutic potential of human-derived endothelial colony-forming cells in animal models. Tissue Eng Part B Rev. 2016;22(5):371–82. https://doi.org/10.1089/ten.TEB.2016.0050 Comprehensive review of in vivo studies indicating the potential use of human-derived ECFCs to induce neovascularization for tissue regeneration.
Critser PJ, Yoder MC. Endothelial colony-forming cell role in neoangiogenesis and tissue repair. Curr Opin Organ Transplant. 2010;15(1):68–72. https://doi.org/10.1097/MOT.0b013e32833454b5.
Tura O, Skinner EM, Barclay GR, Samuel K, Gallagher RC, Brittan M, et al. Late outgrowth endothelial cells resemble mature endothelial cells and are not derived from bone marrow. Stem Cells. 2013;31(2):338–48. https://doi.org/10.1002/stem.1280.
•• Paschalaki KE, Randi AM. Recent advances in endothelial colony forming cells toward their use in clinical translation. Front Med (Lausanne). 2018;5:295. https://doi.org/10.3389/fmed.2018.00295 Recent review of the translational applications of ECFC under investigation of preclinical models for autologous cell therapy, gene therapy, and tissue bioengineering.
Banno K, Yoder MC. Tissue regeneration using endothelial colony-forming cells: promising cells for vascular repair. Pediatr Res. 2018;83(1–2):283–90. https://doi.org/10.1038/pr.2017.231.
•• Keighron C, Lyons CJ, Creane M, O’Brien T, Liew A. Recent advances in endothelial progenitor cells toward their use in clinical translation. Front Med (Lausanne). 2018;5:354. https://doi.org/10.3389/fmed.2018.00354 Comprehensive review of clinical and preclinical studies using the term “EPC,” calling for prudent use of EPC by researchers.
Jimenez-Quevedo P, Gonzalez-Ferrer JJ, Sabate M, Garcia-Moll X, Delgado-Bolton R, Llorente L, et al. Selected CD133(+) progenitor cells to promote angiogenesis in patients with refractory angina: final results of the PROGENITOR randomized trial. Circ Res. 2014;115(11):950–60. https://doi.org/10.1161/CIRCRESAHA.115.303463.
Arici V, Perotti C, Fabrizio C, Del Fante C, Ragni F, Alessandrino F, et al. Autologous immuno magnetically selected CD133+ stem cells in the treatment of no-option critical limb ischemia: clinical and contrast enhanced ultrasound assessed results in eight patients. J Transl Med. 2015;13:342. https://doi.org/10.1186/s12967-015-0697-4.
Mutirangura P, Ruangsetakit C, Wongwanit C, Chinsakchai K, Porat Y, Belleli A, et al. Enhancing limb salvage by non-mobilized peripheral blood angiogenic cell precursors therapy in patients with critical limb ischemia. J Med Assoc Thail. 2009;92(3):320–7.
Kawamoto A, Katayama M, Handa N, Kinoshita M, Takano H, Horii M, et al. Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial. Stem Cells. 2009;27(11):2857–64. https://doi.org/10.1002/stem.207.
Kinoshita M, Fujita Y, Katayama M, Baba R, Shibakawa M, Yoshikawa K, et al. Long-term clinical outcome after intramuscular transplantation of granulocyte colony stimulating factor-mobilized CD34 positive cells in patients with critical limb ischemia. Atherosclerosis. 2012;224(2):440–5. https://doi.org/10.1016/j.atherosclerosis.2012.07.031.
Wang XX, Zhang FR, Shang YP, Zhu JH, Xie XD, Tao QM, et al. Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: a pilot randomized controlled trial. J Am Coll Cardiol. 2007;49(14):1566–71. https://doi.org/10.1016/j.jacc.2006.12.037.
Granton J, Langleben D, Kutryk MB, Camack N, Galipeau J, Courtman DW, et al. Endothelial NO-synthase gene-enhanced progenitor cell therapy for pulmonary arterial hypertension: the PHACeT trial. Circ Res. 2015;117(7):645–54. https://doi.org/10.1161/CIRCRESAHA.114.305951.
D’Avola D, Fernandez-Ruiz V, Carmona-Torre F, Mendez M, Perez-Calvo J, Prosper F, et al. Phase 1-2 pilot clinical trial in patients with decompensated liver cirrhosis treated with bone marrow-derived endothelial progenitor cells. Transl Res. 2017;188:80–91 e2. https://doi.org/10.1016/j.trsl.2016.02.009.
Maldonado GE, Perez CA, Covarrubias EE, Cabriales SA, Leyva LA, Perez JC, et al. Autologous stem cells for the treatment of post-mastectomy lymphedema: a pilot study. Cytotherapy. 2011;13(10):1249–55. https://doi.org/10.3109/14653249.2011.594791.
Lara-Hernandez R, Lozano-Vilardell P, Blanes P, Torreguitart-Mirada N, Galmes A, Besalduch J. Safety and efficacy of therapeutic angiogenesis as a novel treatment in patients with critical limb ischemia. Ann Vasc Surg. 2010;24(2):287–94. https://doi.org/10.1016/j.avsg.2009.10.012.
Tanaka R, Masuda H, Kato S, Imagawa K, Kanabuchi K, Nakashioya C, et al. Autologous G-CSF-mobilized peripheral blood CD34+ cell therapy for diabetic patients with chronic nonhealing ulcer. Cell Transplant. 2014;23(2):167–79. https://doi.org/10.3727/096368912X658007.
Zhu J, Song J, Yu L, Zheng H, Zhou B, Weng S, et al. Safety and efficacy of autologous thymosin beta4 pre-treated endothelial progenitor cell transplantation in patients with acute ST segment elevation myocardial infarction: a pilot study. Cytotherapy. 2016;18(8):1037–42. https://doi.org/10.1016/j.jcyt.2016.05.006.
Zhu JH, Wang XX, Zhang FR, Shang YP, Tao QM, Zhu JH, et al. Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: open-label pilot study. Pediatr Transplant. 2008;12(6):650–5. https://doi.org/10.1111/j.1399-3046.2007.00863.x.
Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature. 2011;469(7330):415–8. https://doi.org/10.1038/nature09637.
Beumer J, Clevers H. Regulation and plasticity of intestinal stem cells during homeostasis and regeneration. Development. 2016;143(20):3639–49. https://doi.org/10.1242/dev.133132.
Sawai CM, Babovic S, Upadhaya S, Knapp D, Lavin Y, Lau CM, et al. Hematopoietic stem cells are the major source of multilineage hematopoiesis in adult animals. Immunity. 2016;45(3):597–609. https://doi.org/10.1016/j.immuni.2016.08.007.
Gonzales KAU, Fuchs E. Skin and its regenerative powers: an alliance between stem cells and their niche. Dev Cell. 2017;43(4):387–401. https://doi.org/10.1016/j.devcel.2017.10.001.
Cheung TH, Rando TA. Molecular regulation of stem cell quiescence. Nat Rev Mol Cell Biol. 2013;14(6):329–40. https://doi.org/10.1038/nrm3591.
Schwartz SM, Benditt EP. Clustering of replicating cells in aortic endothelium. Proc Natl Acad Sci U S A. 1976;73(2):651–3.
Kunz J, Schreiter B, Schubert B, Voss K, Krieg K. Experimental investigations on the regeneration of aortic endothelial cells. Automatic and visual evaluation of autoradiograms (author’s transl). Acta Histochem. 1978;61(1):53–63.
Prescott MF, Muller KR. Endothelial regeneration in hypertensive and genetically hypercholesterolemic rats. Arteriosclerosis. 1983;3(3):206–14.
Manderson JA, Campbell GR. Venous response to endothelial denudation. Pathology. 1986;18(1):77–87.
Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183(4):1797–806.
• Yu QC, Song W, Wang D, Zeng YA. Identification of blood vascular endothelial stem cells by the expression of protein C receptor. Cell Res. 2016;26(10):1079–98. https://doi.org/10.1038/cr.2016.85 Identifies Procr expressing endothelial cells as VESCs in the adult mammary, skin, and retina and provides evidence that Procr+ VESCs are bipotent cells of endothelial cells and pericytes.
• He L, Vanlandewijck M, Mae MA, Andrae J, Ando K, Del Gaudio F, et al. Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types. Sci Data. 2018;5:180160. https://doi.org/10.1038/sdata.2018.160 Provides the database constituting a comprehensive molecular atlas of vascular and vessel-associated cell types in the mouse brain and lung.
•• Sabbagh MF, Heng JS, Luo C, Castanon RG, Nery JR, Rattner A, et al. Transcriptional and epigenomic landscapes of CNS and non-CNS vascular endothelial cells. Elife. 2018;7:e36187. https://doi.org/10.7554/eLife.36187 Demonstrates the comparison of the transcriptome, accessible chromatin, and DNA methylome landscapes from mouse brain, liver, lung, and kidney ECs and provides the evidence of inter-tissue and intra-tissue EC heterogeneity.
Critser PJ, Voytik-Harbin SL, Yoder MC. Isolating and defining cells to engineer human blood vessels. Cell Prolif. 2011;44(Suppl 1):15–21. https://doi.org/10.1111/j.1365-2184.2010.00719.x.
Melero-Martin JM, Khan ZA, Picard A, Wu X, Paruchuri S, Bischoff J. In vivo vasculogenic potential of human blood-derived endothelial progenitor cells. Blood. 2007;109(11):4761–8. https://doi.org/10.1182/blood-2006-12-062471.
Hirschi KK, Dejana E. Resident endothelial progenitors make themselves at home. Cell Stem Cell. 2018;23(2):153–5. https://doi.org/10.1016/j.stem.2018.07.014.
• Campanelli R, Codazzi AC, Poletto V, Abba C, Catarsi P, Fois G, et al. Kinetic and angiogenic activity of circulating endothelial colony forming cells in patients with infantile haemangioma receiving propranolol. Thromb Haemost. 2019;119:274–84. https://doi.org/10.1055/s-0038-1676855. Provides the evaluation of the frequency of circulating ECFCs in patients with IH before and after receiving propranolol and implicates their role in IH pathogenesis.
Baker CD, Balasubramaniam V, Mourani PM, Sontag MK, Black CP, Ryan SL, et al. Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia. Eur Respir J. 2012;40(6):1516–22. https://doi.org/10.1183/09031936.00017312.
Borghesi A, Massa M, Campanelli R, Bollani L, Tzialla C, Figar TA, et al. Circulating endothelial progenitor cells in preterm infants with bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2009;180(6):540–6. https://doi.org/10.1164/rccm.200812-1949OC.
Alphonse RS, Vadivel A, Fung M, Shelley WC, Critser PJ, Ionescu L, et al. Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth. Circulation. 2014;129(21):2144–57. https://doi.org/10.1161/CIRCULATIONAHA.114.009124.
Margariti A, Winkler B, Karamariti E, Zampetaki A, Tsai TN, Baban D, et al. Direct reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelialization in tissue-engineered vessels. Proc Natl Acad Sci U S A. 2012;109(34):13793–8. https://doi.org/10.1073/pnas.1205526109.
Ginsberg M, James D, Ding BS, Nolan D, Geng F, Butler JM, et al. Efficient direct reprogramming of mature amniotic cells into endothelial cells by ETS factors and TGFbeta suppression. Cell. 2012;151(3):559–75. https://doi.org/10.1016/j.cell.2012.09.032.
Morita R, Suzuki M, Kasahara H, Shimizu N, Shichita T, Sekiya T, et al. ETS transcription factor ETV2 directly converts human fibroblasts into functional endothelial cells. Proc Natl Acad Sci U S A. 2015;112(1):160–5. https://doi.org/10.1073/pnas.1413234112.
• Lee S, Park C, Han JW, Kim JY, Cho K, Kim EJ, et al. Direct reprogramming of human dermal fibroblasts into endothelial cells using ER71/ETV2. Circ Res. 2017;120(5):848–61. https://doi.org/10.1161/CIRCRESAHA.116.309833 Utilizes various combinations of seven EC transcriptional factors and demonstrates ETV2 alone can directly reprogram human postnatal cells to functional, mature ECs.
Wareing S, Mazan A, Pearson S, Gottgens B, Lacaud G, Kouskoff V. The Flk1-Cre-mediated deletion of ETV2 defines its narrow temporal requirement during embryonic hematopoietic development. Stem Cells. 2012;30(7):1521–31. https://doi.org/10.1002/stem.1115.
Moore JC, Sheppard-Tindell S, Shestopalov IA, Yamazoe S, Chen JK, Lawson ND. Post-transcriptional mechanisms contribute to Etv2 repression during vascular development. Dev Biol. 2013;384(1):128–40. https://doi.org/10.1016/j.ydbio.2013.08.028.
•• Gallego-Perez D, Pal D, Ghatak S, Malkoc V, Higuita-Castro N, Gnyawali S, et al. Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue. Nat Nanotechnol. 2017;12(10):974–9. https://doi.org/10.1038/nnano.2017.134 Demonstrates a novel non-viral approach to topically reprogram tissue through a nanochannelled device to reprogram keratinocytes into neurons or ECs.
Prasain N, Lee MR, Vemula S, Meador JL, Yoshimoto M, Ferkowicz MJ, et al. Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells. Nat Biotechnol. 2014;32(11):1151–7. https://doi.org/10.1038/nbt.3048.
Sriram G, Tan JY, Islam I, Rufaihah AJ, Cao T. Efficient differentiation of human embryonic stem cells to arterial and venous endothelial cells under feeder- and serum-free conditions. Stem Cell Res Ther. 2015;6:261. https://doi.org/10.1186/s13287-015-0260-5.
• Harding A, Cortez-Toledo E, Magner NL, Beegle JR, Coleal-Bergum DP, Hao D, et al. Highly efficient differentiation of endothelial cells from pluripotent stem cells requires the MAPK and the PI3K pathways. Stem Cells. 2017;35(4):909–19. https://doi.org/10.1002/stem.2577 Demonstrates the efficient EC differentiation from PSCs and investigates molecular pathways responsible for induction of an EC fate.
• Ohta R, Niwa A, Taniguchi Y, Suzuki NM, Toga J, Yagi E, et al. Laminin-guided highly efficient endothelial commitment from human pluripotent stem cells. Sci Rep. 2016;6:35680. https://doi.org/10.1038/srep35680 Provides the important role and contribution of the extracellular matrix during differentiation from PSCs and demonstrated that a short fragment of laminin 411 yields highly-purified ECs without cell sorting.
•• Paik DT, Tian L, Lee J, Sayed N, Chen IY, Rhee S, et al. Large-scale single-cell RNA-Seq reveals molecular signatures of heterogeneous populations of human induced pluripotent stem cell-derived endothelial cells. Circ Res. 2018;123(4):443–50. https://doi.org/10.1161/CIRCRESAHA.118.312913 Provides single-cell transcriptome of differenting PSCs toward the EC lineage and identifies four subpopulation based on molecular signatures.
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Kimihiko Banno and Mervin C. Yoder each declare no potential conflict of interest.
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Banno, K., Yoder, M.C. Endothelial Stem and Progenitor Cells for Regenerative Medicine. Curr Stem Cell Rep 5, 101–108 (2019). https://doi.org/10.1007/s40778-019-00160-3
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DOI: https://doi.org/10.1007/s40778-019-00160-3