Abstract
Despite numerous efforts to generate vascular tissues that recapitulate the physiological characteristics of native vessels, vascular cell source remains one of the principal challenges in the construction of tissue-engineered vascular grafts (TEVGs). Human pluripotent stem cells, therefore, represent an indispensable source to supply a large production of vascular smooth muscle cells (VSMCs) for cell-based therapy. In particular, human induced pluripotent stem cells (hiPSCs) generated from the same individual have opened up new avenues of achieving patient specificity through the derivation of autologous and immunocompatible VSMCs. This book chapter will detail three representative methods of differentiating hiPSCs into VSMCs that are structurally and functionally mature for TEVG engineering. Luo et al. reported an embryoid body (EB)-based approach to generate a robust, large-scale production of mature, functional hiPSC-derived VSMCs as a cell replacement for vascular tissue engineering. EB formation has an advantage of resembling early embryonic development and allowing cellular interactions in three dimensions. Cheung et al. established a system to produce embryological origin-specific hiPSC-derived VSMCs from the neuroectoderm, lateral plate mesoderm, and paraxial mesoderm lineages in a chemically defined manner. This allows site-specific vascular disease modeling. Moreover, Eoh et al. followed Wanjare et al.’s method to construct hiPSC-derived VSMCs using monolayer cultures of extracellular matrix proteins, with the addition of a pulsatile flow for the secretion of mature, organized elastic fibers. The generation of TEVGs, powered by the unlimited supply of hiPSC-derived VSMCs, has begun a new era in cellular therapy for vascular bypass and defective vessel segment replacement, aimed at addressing millions of cases of cardiovascular diseases across the globe.
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References
Laslett LJ, Alagona P, Clark BA et al (2012) The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology. J Am Coll Cardiol 60:S1–S49. https://doi.org/10.1016/j.jacc.2012.11.002
Akoh JA, Patel N (2010) Infection of hemodialysis arteriovenous grafts. J Vasc Access 11:155–158. https://doi.org/10.1177/112972981001100213
Wu J, Hu C, Tang Z et al (2018) Tissue-engineered vascular grafts: balance of the four major requirements. Colloid Interface Sci Commun 23:34–44. https://doi.org/10.1016/j.colcom.2018.01.005
Luo J, Qin L, Zhao L et al (2020) Tissue-engineered vascular grafts with advanced mechanical strength from human iPSCs. Cell Stem Cell 26:251–261.e8. https://doi.org/10.1016/j.stem.2019.12.012
Bajpai VK, Andreadis ST (2012) Stem cell sources for vascular tissue engineering and regeneration. Tissue Eng Part B Rev 18:405–425. https://doi.org/10.1089/ten.teb.2011.0264
Kretlow JD, Jin Y-Q, Liu W et al (2008) Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells. BMC Cell Biol 9:60. https://doi.org/10.1186/1471-2121-9-60
Ayoubi S, Sheikh SP, Eskildsen TV (2017) Human induced pluripotent stem cell-derived vascular smooth muscle cells: differentiation and therapeutic potential. Cardiovasc Res 113:1282–1293. https://doi.org/10.1093/cvr/cvx125
Dash BC, Jiang Z, Suh C, Qyang Y (2015) Induced pluripotent stem cell-derived vascular smooth muscle cells: methods and application. Biochem J 465:185–194. https://doi.org/10.1042/BJ20141078
Xie C-Q, Zhang J, Villacorta L et al (2007) A highly efficient method to differentiate smooth muscle cells from human embryonic stem cells. Arterioscler Thromb Vasc Biol 27:e311–e312. https://doi.org/10.1161/ATVBAHA.107.154260
Wang Y, Hu J, Jiao J et al (2014) Engineering vascular tissue with functional smooth muscle cells derived from human iPS cells and nanofibrous scaffolds. Biomaterials 35:8960–8969. https://doi.org/10.1016/j.biomaterials.2014.07.011
Dash BC, Levi K, Schwan J et al (2016) Tissue-engineered vascular rings from human iPSC-derived smooth muscle cells. Stem Cell Rep 7:19–28. https://doi.org/10.1016/j.stemcr.2016.05.004
Gui L, Dash BC, Luo J et al (2016) Implantable tissue-engineered blood vessels from human induced pluripotent stem cells. Biomaterials 102:120–129. https://doi.org/10.1016/j.biomaterials.2016.06.010
Wanjare M, Kuo F, Gerecht S (2013) Derivation and maturation of synthetic and contractile vascular smooth muscle cells from human pluripotent stem cells. Cardiovasc Res 97:321–330. https://doi.org/10.1093/cvr/cvs315
Eoh JH, Shen N, Burke JA et al (2017) Enhanced elastin synthesis and maturation in human vascular smooth muscle tissue derived from induced-pluripotent stem cells. Acta Biomater 52:49–59. https://doi.org/10.1016/j.actbio.2017.01.083
Bajpai VK, Mistriotis P, Loh Y-H et al (2012) Functional vascular smooth muscle cells derived from human induced pluripotent stem cells via mesenchymal stem cell intermediates. Cardiovasc Res 96:391–400. https://doi.org/10.1093/cvr/cvs253
Cheung C, Bernardo AS, Trotter MWB et al (2012) Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility. Nat Biotechnol 30:165–173. https://doi.org/10.1038/nbt.2107
Cheung C, Bernardo AS, Pedersen RA, Sinha S (2014) Directed differentiation of embryonic origin–specific vascular smooth muscle subtypes from human pluripotent stem cells. Nat Protoc 9:929–938. https://doi.org/10.1038/nprot.2014.059
Patsch C, Challet-Meylan L, Thoma EC et al (2015) Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells. Nat Cell Biol 17:994–1003. https://doi.org/10.1038/ncb3205
Vallier L, Touboul T, Chng Z et al (2009) Early cell fate decisions of human embryonic stem cells and mouse epiblast stem cells are controlled by the same signalling pathways. PLoS One 4(e):6082. https://doi.org/10.1371/journal.pone.0006082
Bernardo AS, Faial T, Gardner L et al (2011) BRACHYURY and CDX2 mediate BMP-induced differentiation of human and mouse pluripotent stem cells into embryonic and extraembryonic lineages. Cell Stem Cell 9:144–155. https://doi.org/10.1016/j.stem.2011.06.015
Hinderer S, Seifert J, Votteler M et al (2014) Engineering of a bio-functionalized hybrid off-the-shelf heart valve. Biomaterials 35:2130–2139. https://doi.org/10.1016/j.biomaterials.2013.10.080
Hinderer S, Shena N, Ringuette L-J et al (2015) In vitro elastogenesis: instructing human vascular smooth muscle cells to generate an elastic fiber-containing extracellular matrix scaffold. Biomed Mater Bristol Engl 10:034102. https://doi.org/10.1088/1748-6041/10/3/034102
Vo E, Hanjaya-Putra D, Zha Y et al (2010) Smooth-muscle-like cells derived from human embryonic stem cells support and augment cord-like structures in vitro. Stem Cell Rev Rep 6:237–247. https://doi.org/10.1007/s12015-010-9144-3
Gerecht-Nir S, Ziskind A, Cohen S, Itskovitz-Eldor J (2003) Human embryonic stem cells as an in vitro model for human vascular development and the induction of vascular differentiation. Lab Investig 83:1811–1820. https://doi.org/10.1097/01.LAB.0000106502.41391.F0
Chen P-Y, Qin L, Li G et al (2016) Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation. Sci Rep 6:33407. https://doi.org/10.1038/srep33407
Schlumberger W, Thie M, Rauterberg J, Robenek H (1991) Collagen synthesis in cultured aortic smooth muscle cells. Modulation by collagen lattice culture, transforming growth factor-beta 1, and epidermal growth factor. Arterioscler Thromb 11:1660–1666. https://doi.org/10.1161/01.atv.11.6.1660
Majesky MW (2007) Developmental basis of vascular smooth muscle diversity. Arterioscler Thromb Vasc Biol 27:1248–1258. https://doi.org/10.1161/ATVBAHA.107.141069
Beamish JA, He P, Kottke-Marchant K, Marchant RE (2010) Molecular regulation of contractile smooth muscle cell phenotype: implications for vascular tissue engineering. Tissue Eng Part B Rev 16:467–491. https://doi.org/10.1089/ten.teb.2009.0630
Ryan AJ, O’Brien FJ (2015) Insoluble elastin reduces collagen scaffold stiffness, improves viscoelastic properties, and induces a contractile phenotype in smooth muscle cells. Biomaterials 73:296–307. https://doi.org/10.1016/j.biomaterials.2015.09.003
Lee AA, Graham DA, Dela Cruz S et al (2002) Fluid shear stress-induced alignment of cultured vascular smooth muscle cells. J Biomech Eng 124:37–43. https://doi.org/10.1115/1.1427697
Atchison L, Zhang H, Cao K, Truskey GA (2017) A tissue engineered blood vessel model of Hutchinson-Gilford progeria syndrome using human iPSC-derived smooth muscle cells. Sci Rep 7:8168. https://doi.org/10.1038/s41598-017-08632-4
Deuse T, Hu X, Gravina A et al (2019) Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol 37:252–258. https://doi.org/10.1038/s41587-019-0016-3
Xu H, Wang B, Ono M et al (2019) Targeted disruption of HLA genes via CRISPR-Cas 9 generates iPSCs with enhanced immune compatibility. Cell Stem Cell 24:566–578.e7. https://doi.org/10.1016/j.stem.2019.02.005
Gornalusse GG, Hirata RK, Funk S et al (2017) HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells. Nat Biotechnol 35:765–772. https://doi.org/10.1038/nbt.3860
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Li, ML., Luo, J., Ellis, M.W., Riaz, M., Ajaj, Y., Qyang, Y. (2022). Methods for Differentiating hiPSCs into Vascular Smooth Muscle Cells. In: Zhao, F., Leong, K.W. (eds) Vascular Tissue Engineering. Methods in Molecular Biology, vol 2375. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1708-3_3
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