Abstract
Hemangioblasts are progenitors with the capacity to differentiate into hematopoietic, endothelial, smooth muscle, and mesenchymal stromal cells and represent an excellent candidate of cell therapy for a variety of human diseases. To realize their clinical potential, first, an efficient and controlled differentiation toward hemangioblasts in a scalable manner, probably in a bioreactor setting, from an unlimited source is required. These cells also need to be generated under animal components and cell-free conditions, or additional regulatory challenges, such as xeno-transplant, will have to be addressed. The ability of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSC) to divide indefinitely without losing pluripotency may allow them to serve as an inexhaustible source for the large-scale production of therapeutic cells. In this chapter, we describe a robust system that can efficiently generate large numbers of hemangioblasts from multiple hESCs and iPSC lines under well-defined conditions, which is an important step for future clinical applications, with the potential of developing a GMP-compatible scalable system.
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Wagner RC. Endothelial cell embryology and growth. Adv Microcirc. 1980;9:45–75.
Ema M, Faloon P, Zhang WJ, et al. Combinatorial effects of Flk1 and Tal1 on vascular and hematopoietic development in the mouse. Genes Dev. 2003;17:380–93.
DSouza SL, Elefanty AG, Keller G. SCL/Tal-1 is essential for hematopoietic commitment of the hemangioblast but not for its development. Blood 2005;105:3862–3870.
Lu SJ, Ivanova Y, Feng Q, Luo C, Lanza R. Hemangioblasts from human embryonic stem cells generate multilayered blood vessels with functional smooth muscle cells. Regen Med. 2009;4:37–47.
Wang X, Kimbrel EA, Ijichi K, et al. Human ESC-derived MSCs outperform bone marrow MSCs in the treatment of an EAE model of multiple sclerosis. Stem Cell Reports. 2014;3:115–30.
Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–7.
Murohara T, Ikeda H, Duan J, et al. Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest. 2000;105:1527–36.
Hungerford JE, Little CD. Developmental biology of the vascular smooth muscle cell: building a multilayered vessel wall. J Vasc Res. 1999;36:2–27.
Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res. 2001;49:507–21.
Biomedicine Carmeliet P. Clotting factors build blood vessels. Science. 2001;293:1602–4.
Choi K, Kennedy M, Kazarov A, Papadimitriou JC, Keller G. A common precursor for hematopoietic and endothelial cells. Development. 1998;125:725–32.
Kennedy M, Firpo M, Choi K, et al. A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature. 1997;386:488–93.
Wang L, Li L, Shojaei F, et al. Endothelial and hematopoietic cell fate of human embryonic stem cells originates from primitive endothelium with hemangioblastic properties. Immunity. 2004;21:31–41.
Zambidis ET, Peault B, Park TS, Bunz F, Civin CI. Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development. Blood. 2005;106:860–70.
Umeda K, Heike T, Yoshimoto M, et al. Identification and characterization of hemoangiogenic progenitors during cynomolgus monkey embryonic stem cell differentiation. Stem Cells. 2006;24:1348–58.
Kennedy M, D’Souza SL, Lynch-Kattman M, Schwantz S, Keller G. Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures. Blood. 2007;109:2679–87.
Lu SJ, Feng Q, Caballero S, et al. Generation of functional hemangioblasts from human embryonic stem cells. Nat Methods. 2007;4:501–9.
Lu SJ, Luo C, Holton K, et al. Robust generation of hemangioblastic progenitors from human embryonic stem cells. Regen. Med. 2008;3:693–704.
Lu SJ, Kelley T, Feng Q, et al. 3D microcarrier system for efficient differentiation of human pluripotent stem cells into hematopoietic cells without feeders and serum [corrected]. Regen Med. 2013;8:413–24.
Oh SK, Chen AK, Mok Y, et al. Long-term microcarrier suspension cultures of human embryonic stem cells. Stem Cell Res. 2009;2:219–30.
Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R. Derivation of human embryonic stem cells from single blastomeres. Nat Protoc. 2007;2:1963–72.
Klimanskaya I, McMahon J. Approaches of derivation and maintenance of human ES cells: detailed procedures and alternatives. In: Lanza Rea, ed. Handbook of Stem Cells. Volume 1: Embryonic Stem Cells. New York, USA: Elsevier/Academic Press; 2004:437–449.
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Lu, SJ., Feng, Q., Lanza, R. (2015). Generation of Hemangioblasts from Human Pluripotent Stem Cells. In: Cheng, T. (eds) Hematopoietic Differentiation of Human Pluripotent Stem Cells. SpringerBriefs in Stem Cells, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7312-6_1
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DOI: https://doi.org/10.1007/978-94-017-7312-6_1
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