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Induced pluripotency in the context of stem cell expansion bioprocess development, optimization, and manufacturing: a roadmap to the clinic

  • 1.

    Kirouac, D. C. & Zandstra, P. W. The systematic production of cells for cell therapies. Cell Stem Cell 3, 369–381 (2008).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 2.

    Jenkins, M. J. & Farid, S. S. Human pluripotent stem cell-derived products: advances towards robust, scalable and cost-effective manufacturing strategies. Biotechnol. J. 10, 83–95 (2014).

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar 

  • 3.

    Adil, M. M. & Schaffer, D. V. Expansion of human pluripotent stem cells. Curr. Opin. Chem. Eng. 15, 24–35 (2017).

    Article 

    Google Scholar 

  • 4.

    Kempf, H., Andree, B. & Zweigerdt, R. Large-scale production of human pluripotent stem cell derived cardiomyocytes. Adv. Drug Deliv. Rev. 96, 18–30 (2016).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 5.

    Kropp, C., Massai, D. & Zweigerdt, R. Progress and challenges in large-scale expansion of human pluripotent stem cells. Process Biochem. 59, 244–254 (2017).

    CAS 
    Article 

    Google Scholar 

  • 6.

    Pellegrini, G. et al. From discovery to approval of an advanced therapy medicinal product-containing stem cells, in the EU. Regen. Med. 11, 407–420 (2016).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 7.

    Yin, X. et al. Stem cell organoid engineering. Cell Stem Cell 18, 25–38 (2016).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 8.

    Chen, K. G. et al. Pluripotent stem cell platforms for drug discovery. Trends Mol. Med. 24, 805–820 (2018).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 9.

    Romito, A. & Cobellis, G. Pluripotent stem cells: current understanding and future directions. Stem Cells Int. 2016, 1–20 (2016).

    Article 

    Google Scholar 

  • 10.

    Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147 (1998).

    CAS 
    Article 

    Google Scholar 

  • 11.

    Caulfield, T. et al. International stem cell environments: a world of difference. Nat. Rep. Stem Cells 1, 1–5 (2009).

    Google Scholar 

  • 12.

    Kim, K. et al. Epigenetic memory in induced pluripotent stem cells. Nature 467, 285–290 (2010).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 13.

    Robinton, D. A. & Daley, G. Q. The promise of induced pluripotent stem cells in research and therapy. Nature 481, 295–305 (2012).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 14.

    Flavahan, W. A., Gaskell, E. & Bernstein, B. E. Epigenetic plasticity and the hallmarks of cancer. Science 357, 1–9 (2017).

    Article 
    CAS 

    Google Scholar 

  • 15.

    Volarevic, V. et al. Ethical and safety issues of stem cell-based therapy. Int. J. Med. Sci. 15, 36–45 (2018).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 16.

    Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).

    CAS 
    Article 

    Google Scholar 

  • 17.

    Bai, L. et al. Hepatocyte growth factor mediates mesenchymal stem cell-induced recovery in multiple sclerosis models. Nat. Neurosci. 15, 862–870 (2012).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 18.

    Trounson, A. & McDonald, C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 17, 11–22 (2015).

    CAS 
    Article 

    Google Scholar 

  • 19.

    Garbern, J. C. & Lee, R. T. Cardiac stem cell therapy and the promise of heart regeneration. Cell Stem Cell 12, 689–698 (2013).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 20.

    Trounson, A. & DeWitt, N. D. Pluripotent stem cells progressing to the clinic. Nat. Rev. Mol. Cell Biol. 17, 194–200 (2016).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 21.

    Braganca, J., Lopes, J. A., Mendes-Silva, L. & Santos, J. M. A. Induced pluripotent stem cells, a giant leap for mankind therapeutic applications. World J. Stem Cells 11, 421–430 (2019).

    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 22.

    Kim, M. & Kino-oka, M. Bioengineering considerations for a nurturing way to enhance scalable expansion of human pluripotent stem cells. Biotechnol. J. 15, 1–16 (2020).

    Google Scholar 

  • 23.

    Wu, S. M. & Hochedlinger, K. Harnessing the potential of induced pluripotent stem cells for regenerative medicine. Nat. Cell Biol. 13, 497–505 (2011).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 24.

    Lund, R. J., Narva, E. & Lahesmaa, R. Understanding the genetics behind complex human disease with large-scale iPSC collections. Nat. Rev. Genet. 13, 732–744 (2012).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 25.

    Popp, B. et al. Need for high-resolution Genetic Analysis in iPSC: results and lessons from the ForIPS consortium. Sci. Rep. 8, 1–14 (2018).

    CAS 
    Article 

    Google Scholar 

  • 26.

    Liang, G. & Zhang, Y. Genetic and epigenetic variations in iPSCs: potential causes and implications for application. Cell Stem Cell 13, 149–159 (2013).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 27.

    Merkle, F. T. et al. Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations. Nature 545, 229–233 (2017).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 28.

    Cao, J. et al. Cells derived from iPSC can be immunogenic—yes or no? Protein Cell 5, 1–3 (2014).

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar 

  • 29.

    Liu, X., Li, W., Fu, X. & Xu, Y. The immunogenicity and immune tolerance of pluripotent stem cell derivatives. Front. Immunol. 8, 1–6 (2017).

    Google Scholar 

  • 30.

    Chhabra, A. Inherent immunogenicity or lack thereof of pluripotent stem cells: implications for cell replacement therapy. Front. Immunol. 8, 1–11 (2017).

    Article 
    CAS 

    Google Scholar 

  • 31.

    Pera, M. F. Stem cells: the dark side of induced pluripotency. Nature 471, 46–47 (2011).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 32.

    Nishino, K. et al. DNA methylation dynamics in human induced pluripotent stem cells over time. PLoS Genet. 7, 1–14 (2011).

    Article 
    CAS 

    Google Scholar 

  • 33.

    Youssef, A. A. et al. The promise and challenge of induced pluripotent stem cells for cardiovascular applications. JACC Basic Transl. Sci. 1, 510–523 (2016).

    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 34.

    D’Urso, A. & Brickner, J. H. Mechanisms of epigenetic memory. Trends Genet. 30, 230–236 (2014).

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar 

  • 35.

    Khoo, T. S. et al. Retention of somatic memory associated with cell identity, age and metabolism in induced pluripotent stem (iPS) cells reprogramming. Stem Cell Rev. Rep. 16, 251–261 (2020).

    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 36.

    Lee, J. E. & Lee, D. R. Human embryonic stem cells: derivation, maintenance and cryopreservation. Int. J. Stem Cells 4, 1–8 (2011).

    Article 

    Google Scholar 

  • 37.

    Yamanaka, S. Induced pluripotent stem cells: past, present, and future. Cell Stem Cell 10, 678–684 (2012).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 38.

    Kyttala, A. et al. Genetic variability overrides the impact of parental cell type and determines iPSC differentiation potential. Stem Cell Rep. 6, 200–212 (2016).

    Article 

    Google Scholar 

  • 39.

    Kim, M. & Costello, J. DNA methylation: an epigenetic mark of cellular memory. Exp. Mol. Med. 49, 1–8 (2017).

    CAS 

    Google Scholar 

  • 40.

    Nishizawa, M. et al. Epigenetic variation between human induced pluripotent stem cell lines is an indicator of differentiation capacity. Cell Stem Cell 19, 341–354 (2016).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 41.

    Schwartzentruber, J. et al. Molecular and functional variation in iPSC-derived sensory neurons. Nat. Genet. 50, 54–61 (2018).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 42.

    Anguera, M. C. et al. Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes. Cell Stem Cell 11, 75–90 (2012).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 43.

    Ronen, D. & Benvenisty, N. Sex-dependent gene expression in human pluripotent stem cells. Cell Stem Cell 8, 923–932 (2014).

    CAS 

    Google Scholar 

  • 44.

    Rubin, J. B. et al. Sex differences in cancer mechanisms. Biol. Sex. Differences 11, 1–29 (2020).

    Article 
    CAS 

    Google Scholar 

  • 45.

    Kass, S. U., Pruss, D. & Wolffe, A. P. How does DNA methylation repress transcription? Trends Genet. 13, 444–449 (1997).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 46.

    Perrera, V. & Martello, G. How does reprogramming to pluripotency affect genomic imprinting? Front. Cell Dev. Biol. 7, 1–16 (2019).

    Article 

    Google Scholar 

  • 47.

    Pick, M. et al. Clone‐ and gene‐specific aberrations of parental imprinting in human induced pluripotent stem cells. Stem Cells 27, 2686–2690 (2009).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 48.

    Panoupoulos, A. D. et al. Aberrant DNA methylation in human iPSCs associates with MYC-binding motifs in a clone-specific manner independent of genetics. Cell Stem Cell 20, 505–517 (2017).

    Article 
    CAS 

    Google Scholar 

  • 49.

    Assou, S. et al. Recurrent genetic abnormalities in human pluripotent stem cells: definition and routine detection in culture supernatant by targeted droplet digital PCR. Stem Cell Rep. 14, 1–8 (2020).

    CAS 
    Article 

    Google Scholar 

  • 50.

    Lessard, J. A. & Crabtree, G. R. Chromatin regulatory mechanisms in pluripotency. Annu. Rev. Cell Dev. Biol. 26, 503–532 (2010).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 51.

    Collier, A. J. & Rugg-Gunn, P. J. Identifying human naïve pluripotent stem cells−evaluating state‐specific reporter lines and cell‐surface markers. Bioessays 40, 1–12 (2018).

    Article 

    Google Scholar 

  • 52.

    Efroni, S. et al. Global transcription in pluripotent embryonic stem cells. Cell Stem Cell 2, 437–447 (2008).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 53.

    Harvey, A. et al. Interplay between metabolites and the epigenome in regulating embryonic and adult stem cell potency and maintenance. Stem Cell Rep. 13, 573–589 (2019).

    CAS 
    Article 

    Google Scholar 

  • 54.

    Kapinas, K. et al. The abbreviated pluripotent cell cycle. J. Cell Physiol. 1, 9–20 (2013).

    Article 
    CAS 

    Google Scholar 

  • 55.

    Mathieu, J. & Ruohola-Baker, H. Metabolic remodeling during the loss and acquisition of pluripotency. Development 144, 541–555 (2017).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 56.

    Hassani, S. et al. Inhibition of TGFβ signaling promotes ground state pluripotency. Stem Cell Rev. Rep. 10, 16–30 (2014).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 57.

    Burgess, R. J., Agathocleous, M. & Morrison, S. J. Metabolic regulation of stem cell function. J. Intern. Med. 276, 12–24 (2014).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 58.

    Carey, B. W. et al. Reprogramming factor stoichiometry influences the epigenetic state and biological properties of induced pluripotent stem cells. Cell Stem Cell 6, 588–598 (2011).

    Article 
    CAS 

    Google Scholar 

  • 59.

    Baker, D. et al. Detecting genetic mosaicism in cultures of human pluripotent stem cells. Stem Cell Rep. 7, 998–1012 (2016).

    CAS 
    Article 

    Google Scholar 

  • 60.

    Wu, J., Yamauchi, T. & Belmonte, J. C. I. An overview of mammalian pluripotency. Development 143, 1644–1648 (2016).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 61.

    Pennings, S., Liu, K. J. & Qian, H. The stem cell niche: interactions between stem cells and their environment. Stem Cells Int. 2018, 1–3 (2018).

    Article 
    CAS 

    Google Scholar 

  • 62.

    Efthymiou, A. G., Chen, G., Rao, M., Chen, G. & Boehm, M. Self-renewal and cell lineage differentiation strategies in human embryonic stem cells and induced pluripotent stem cells. Expert Opin. Biol. Ther. 14, 1333–1344 (2014).

    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 63.

    Liu, X. et al. Reprogramming roadmap reveals route to human induced trophoblast stem cells. Nature 586, 101–107 (2020).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 64.

    Liu, M., Liu, N., Zang, R., Li, Y. & Yang, S. Engineering stem cell niches in bioreactors. World J. Stem Cells 5, 124–135 (2013).

    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 65.

    Kilens, S. et al. Parallel derivation of isogenic human primed and naive induced pluripotent stem cells. Nat. Commun. 9, 1–13 (2018).

    CAS 
    Article 

    Google Scholar 

  • 66.

    Saito, S. et al. Emerging roles of hypoxia-inducible factors and reactive oxygen species in cancer and pluripotent stem cells. Kaohsiung J. Med. Sci. 31, 279–286 (2015).

    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 67.

    Borys, B. S. et al. Optimized serial expansion of human induced pluripotent stem cells using low‐density inoculation to generate clinically relevant quantities in vertical‐wheel bioreactors. Stem Cells Transl. Med. 9, 1036–1052 (2020).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 68.

    Assou, S., Bouckenheimer, J. & De Vos, J. Concise Review: assessing the genome integrity of human induced pluripotent stem cells: what quality control metrics? Stem Cells Transl. Med. 36, 814–821 (2018).

    CAS 
    Article 

    Google Scholar 

  • 69.

    Buta, C. et al. Reconsidering pluripotency tests: do we still need teratoma assays? Stem Cell Res. 11, 552–562 (2013).

    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 70.

    Mao, A. S. & Mooney, D. J. Regenerative medicine: current therapies and future directions. Proc. Natl Acad. Sci. USA 112, 14452–14459 (2015).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 71.

    Li, K., Zhang, M., Xie, F., Liu, P. & Xu, S. Differentiation of pluripotent stem cells for regenerative medicine. Biochem. Biophys. Res. Commun. 471, 1–4 (2016).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 72.

    Joddar, B. & Ito, Y. Artificial niche substrates for embryonic and induced pluripotent stem cell cultures. J. Biotechnol. 168, 218–228 (2013).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 73.

    Baghbaderani, B. A. et al. Detailed characterization of human induced pluripotent stem cells manufactured for therapeutic applications. Stem Cell Rev. Rep. 12, 394–420 (2016).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 74.

    Sart, S., Bejoy, J. & Li, Y. Characterization of 3D pluripotent stem cell aggregates and the impact of their properties on bioprocessing. Process Biochem. 59, 276–288 (2017).

    CAS 
    Article 

    Google Scholar 

  • 75.

    Galvanauskas, V. et al. Current state and perspectives in modeling and control of human pluripotent stem cell expansion processes in stirred-tank bioreactors. Biotechnol. Prog. 33, 355–364 (2017).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 76.

    Polanco, A., Kuang, B. & Yoon, S. Bioprocess technologies that preserve the quality of iPSCs. Trends Biotechnol. 38, 1128–1140 (2020).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 77.

    Tohyama, S. et al. Efficient large-scale 2D culture system for human induced pluripotent stem cells and differentiated cardiomyocytes. Stem Cell Rep. 9, 1406–1414 (2017).

    CAS 
    Article 

    Google Scholar 

  • 78.

    Lavon, N., Zimerman, M. & Itskovitz-Eldor, J. In Advances in Biochemical Engineering/Biotechnology Book Series, ABE 163, 22–37 (2017). Edited by Scheper, T., Zhong, J. Published by Springer-Verlag Berlin Heidelberg NewYork.

  • 79.

    Oyetunde, T., Bao, F. S., Chen, J. W., Martin, H. C. & Tang, Y. J. Leveraging knowledge engineering and machine learning for microbial manufacturing. Biotechnol. Adv. 36, 1308–1315 (2018).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 80.

    Zitnik, M. et al. Machine learning for integrating data in biology and medicine: principles, practice, and opportunities. Inf. Fusion 50, 71–91 (2019).

    Article 

    Google Scholar 

  • 81.

    Doulgkeroglou, M. et al. Automation, monitoring, and standardization of cell product manufacturing. Front. Bioeng. Biotechnol. 8, 1–12 (2020).

    Article 

    Google Scholar 

  • 82.

    Malta, T. M. et al. Machine learning identifies stemness features associated with oncogenic dedifferentiation. Cell 173, 338–354 (2018).

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar 

  • 83.

    Sugimoto, K. Machine learning-driven label-free cell sorting for CAR-T cell manufacturing. Cytotherapy 21, S39 (2019).

    Article 

    Google Scholar 

  • 84.

    Williams, B. et al. Prediction of human induced pluripotent stem cell cardiac differentiation outcome by multifactorial process modeling. Front. Bioeng. Biotechnol. 8, 1–15 (2020).

    Article 

    Google Scholar 

  • 85.

    Kobold, S. et al. A manually curated database on clinical studies involving cell products derived from human pluripotent stem cells. Stem Cell Rep. 15, 546–555 (2020).

    CAS 
    Article 

    Google Scholar 

  • 86.

    Deinsberger, J., Reisinger, D. & Weber, B. Global trends in clinical trials involving pluripotent stem cells: a systematic multi-database analysis. npj Regen. Med. 5, 1–13 (2020).

    Article 

    Google Scholar 

  • 87.

    Sung, Y. et al. Long-term safety and tolerability of subretinal transplantation of embryonic stem cell-derived retinal pigment epithelium in Asian Stargardt disease patients. Br. J. Opthalmol. 105, 829–837 (2021).

    Article 

    Google Scholar 

  • 88.

    Mandai, M. et al. Autologous induced stem cell-derived retinal cells for macular degeneration. N. Engl. J. Med. 376, 1038–1046 (2017).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 89.

    Bloor, A. J. C. et al. Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study. Nat. Med. 26, 1720–1725 (2020).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 90.

    Doss, M. X. & Sachinidis, A. Current challenges of iPSC-based modeling and therapeutic implications. Cells 8, 1–16 (2019).

    Article 
    CAS 

    Google Scholar 

  • 91.

    Dashtban, M., Panchalingam, K. M., Shafa, M. & Baghbaderani, B. A. Addressing manufacturing challenges for commercialization of iPSC-based therapies. Methods Mol. Biol. 2286, 179–198 (2021).

    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 92.

    Yamanaka, S. Pluripotent stem cell-based cell therapy – promise and challenges. Cell Stem Cell 27, 523–531 (2020).

    CAS 
    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 93.

    Ozay, E. I. et al. Cymerus iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease. Stem Cell Res. 35, 1–13 (2019).

    Article 
    CAS 

    Google Scholar 

  • 94.

    Menasche, P. et al. Transplantation of human embryonic stem cell-derived cardiovascular progenitors for severe ischemic left ventricular dysfunction. J. Am. Coll. Cardiol. 71, 429–438 (2018).

    PubMed 
    Article 
    PubMed Central 

    Google Scholar 

  • 95.

    Kamao, H. et al. Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Rep. 2, 205–218 (2014).

    CAS 
    Article 

    Google Scholar 

  • 96.

    Wang, Y. et al. Human clinical-grade parthenogenetic ESC-derived dopaminergic neurons recover locomotive defects of nonhuman primate models of Parkinson’s disease. Stem Cell Rep. 11, 171–182 (2018).

    CAS 
    Article 

    Google Scholar 

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