The Challenge of Bringing iPSCs to the Patient
Abstract
:1. The Evolution of a Revolution
2. The Giant Leap from the Lab to the Clinics
2.1. Indirect Uses of iPSCs: a Helpful Tool for the Patient
2.1.1. Platelet Factory
2.1.2. The New Age of Drug Discovery
2.2. The Potential of iPS Cell-Based Therapeutics
2.3. Preclinical Studies and Ongoing Clinical Trials
3. Where We Are and Where We Are Heading to
3.1. Economic Issues
3.2. Genomic Instability, an Old Enemy
3.3. Immunogenicity: the Main Obstacle?
3.4. Biobanking the iPSCs
3.5. Loose Ends in the Clinical iPSCs Application
3.6. A Glimpse of the Future
4. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
iPSCs | induced pluripotent stem cells |
ESCs | embryonic stem cells |
HLA | human leukocyte antigen |
ALS | amyotrophic lateral sclerosis |
FOP | fibrodysplasia ossificans progressiva |
IKAP | IκB kinase complex–associated protein |
OOC | organ-on-a-chip |
MSCs | mesenchymal stem cells |
AMD | age-related macular degeneration |
RPE | retinal pigment epithelium |
CiRA | center for iPS cell research and application |
NK | natural killer |
GVHD | graft-versus-host disease |
MHC | major histocompatibility complex |
References
- Takahashi, K.; Yamanaka, S.; Zhang, Y.; Li, Y.; Feng, C.; Li, X.; Lin, L.; Guo, L.; Wang, H.; Liu, C.; et al. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126, 663–676. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takahashi, K.; Tanabe, K.; Ohnuki, M.; Narita, M.; Ichisaka, T.; Tomoda, K.; Yamanaka, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007, 131, 861–872. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, J.; Vodyanik, M.A.; Smuga-Otto, K.; Antosiewicz-Bourget, J.; Frane, J.L.; Tian, S.; Nie, J.; Jonsdottir, G.A.; Ruotti, V.; Stewart, R.; et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007, 318, 1917–1920. [Google Scholar] [CrossRef] [PubMed]
- Choi, J.; Lee, S.; Clement, K.; Mallard, W.; Tagliazucchi, G.M.; Lim, H.; Choi, I.Y.; Ferrari, F.; Tsankov, A.; Pop, R.; et al. A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs. Nat. Biotechnol. 2016, 25, 289–313. [Google Scholar] [CrossRef]
- Shi, Y.; Inoue, H.; Wu, J.C.; Yamanaka, S. Induced pluripotent stem cell technology: A decade of progress. Nat. Rev. Drug Discov. 2017, 16, 115–130. [Google Scholar] [CrossRef]
- Ratajczak, M.Z.; Bujko, K.; Wojakowski, W. Stem cells and clinical practice: New advances and challenges at the time of emerging problems with induced pluripotent stem cell therapies. Pol. Arch. Med. Wewn. 2016, 126, 879–890. [Google Scholar] [CrossRef]
- Strassel, C.; Gachet, C.; Lanza, F. On the way to in vitro platelet production. Front. Med. 2018, 5, 220–227. [Google Scholar] [CrossRef] [Green Version]
- Sugimoto, N.; Eto, K. Platelet production from induced pluripotent stem cells. J. Thromb. Haemost. 2017, 15, 1717–1727. [Google Scholar] [CrossRef]
- Feng, Q.; Shabrani, N.; Thon, J.N.; Huo, H.; Thiel, A.; Machlus, K.R.; Kim, K.; Brooks, J.; Li, F.; Luo, C.; et al. Scalable generation of universal platelets from human induced pluripotent stem cells. Stem Cell Rep. 2014, 3, 817–831. [Google Scholar] [CrossRef] [Green Version]
- Lawrence, M.; Mueller, A.; Ghevaert, C. Using genome editing to engineer universal platelets. Emerg. Top. Life Sci. 2019, 3, 301–311. [Google Scholar]
- Jang, Y.; Choi, J.; Park, N.; Kang, J.; Kim, M.; Kim, Y.; Ju, J.H. Development of immunocompatible pluripotent stem cells via CRISPR-based human leukocyte antigen engineering. Exp. Mol. Med. 2019, 51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Börger, A.K.; Eicke, D.; Wolf, C.; Gras, C.; Aufderbeck, S.; Schulze, K.; Engels, L.; Eiz-Vesper, B.; Schambach, A.; Guzman, C.; et al. Generation of HLA-universal iPSC-derived megakaryocytes and platelets for survival under refractoriness conditions. Mol. Med. 2016, 22, 274–285. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hansen, M.; von Lindern, M.; van den Akker, E.; Varga, E. Human induced pluripotent stem cell-derived blood products: State of the art and future directions. FEBS Lett. 2019. [Google Scholar] [CrossRef] [PubMed]
- Ito, Y.; Nakamura, S.; Sugimoto, N.; Shigemori, T.; Kato, Y.; Ohno, M.; Sakuma, S.; Ito, K.; Kumon, H.; Hirose, H.; et al. Turbulence activates platelet biogenesis to enable clinical scale ex vivo production. Cell 2018, 174, 636–648. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Engle, S.J.; Puppala, D. Integrating human pluripotent stem cells into drug development. Cell Stem Cell 2013, 12, 669–677. [Google Scholar] [CrossRef] [Green Version]
- McNeish, J.; Gardner, J.P.; Wainger, B.J.; Woolf, C.J.; Eggan, K. From dish to bedside: lessons learned while translating findings from a stem cell model of disease to a clinical trial. Cell Stem Cell 2015, 17, 8–10. [Google Scholar] [CrossRef] [Green Version]
- Kim, J.; Lana, B.; Torelli, S.; Ryan, D.; Catapano, F.; Ala, P.; Luft, C.; Stevens, E.; Konstantinidis, E.; Louzada, S.; et al. A new patient-derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of a-dystroglycan. EMBO Rep. 2019, 20, e47967. [Google Scholar] [CrossRef]
- Kokubu, Y.; Nagino, T.; Sasa, K.; Oikawa, T.; Miyake, K.; Kume, A.; Fukuda, M.; Fuse, H.; Tozawa, R.; Sakurai, H. Phenotypic drug screening for dysferlinopathy using patient-derived induced pluripotent stem cells. Stem Cells Transl. Med. 2019. [Google Scholar] [CrossRef] [Green Version]
- Kotz, J. Phenotypic screening, take two. Sci. Exch. 2012, 5, 380. [Google Scholar] [CrossRef]
- Eder, J.; Sedrani, R.; Wiesmann, C. The discovery of first-in-class drugs: Origins and evolution. Nat. Rev. Drug Discov. 2014, 13, 577–587. [Google Scholar] [CrossRef]
- Swinney, D.C. Phenotypic vs. Target-based drug discovery for first-in-class medicines. Clin. Pharmacol. Ther. 2013, 93, 299–301. [Google Scholar] [CrossRef] [PubMed]
- Lee, G.; Ramirez, C.N.; Kim, H.; Zeltner, N.; Liu, B.; Radu, C.; Bhinder, B.; Kim, Y.J.; Choi, I.Y.; Mukherjee-Clavin, B.; et al. Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression. Nat. Biotechnol. 2012, 30, 1244–1248. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nakajima, T.; Ikeya, M. Insights into the biology of fibrodysplasia ossificans progressiva using patient-derived induced pluripotent stem cells. Regen. Ther. 2019, 11, 25–30. [Google Scholar] [CrossRef] [PubMed]
- Garbes, L.; Heesen, L.; Hölker, I.; Bauer, T.; Schreml, J.; Zimmermann, K.; Thoenes, M.; Walter, M.; Dimos, J.; Peitz, M.; et al. VPA response in SMA is suppressed by the fatty acid translocase CD36. Hum. Mol. Genet. 2013, 22, 398–407. [Google Scholar] [CrossRef] [Green Version]
- Zhang, N.; Bailus, B.J.; Ring, K.L.; Ellerby, L.M. IPSC-based drug screening for Huntingtons disease. Brain Res. 2016, 1638, 42–56. [Google Scholar] [CrossRef] [Green Version]
- Morimoto, S.; Takahashi, S.; Fukushima, K.; Saya, H.; Suzuki, N.; Aoki, M.; Okano, H.; Nakahara, J. Ropinirole hydrochloride remedy for amyotrophic lateral sclerosis–Protocol for a randomized, double-blind, placebo-controlled, single-center, and open-label continuation phase I/IIa clinical trial (ROPALS trial). Regen. Ther. 2019, 11, 143–166. [Google Scholar] [CrossRef]
- Jodat, Y.A.; Kang, M.G.; Kiaee, K.; Kim, G.J.; Martinez, A.F.H.; Rosenkranz, A.; Bae, H.; Shin, S.R. Human-derived organ-on-a-chip for personalized drug development. Curr. Pharm. Des. 2019, 24, 5471–5486. [Google Scholar] [CrossRef]
- Cavero, I.; Guillon, J.-M.; Holzgrefe, H.H. Human organotypic bioconstructs from organ-on-chip devices for human-predictive biological insights on drug candidates. Expert Opin. Drug Saf. 2019, 18, 651–677. [Google Scholar] [CrossRef]
- Mao, A.S.; Mooney, D.J. Regenerative medicine: Current therapies and future directions. Proc. Natl. Acad. Sci. USA 2015, 112, 14452–14459. [Google Scholar] [CrossRef] [Green Version]
- Chun, Y.S.; Byun, K.; Lee, B.C.-. 3254878 Induced pluripotent stem cells and personalized medicine: current progress and future perspectives. Anat Cell Biol. 2011, 44, 245–255. [Google Scholar] [CrossRef] [Green Version]
- Bhagavati, S. Stem Cell Therapy: Challenges Ahead. Indian J. Pediatr. 2015, 82, 286–291. [Google Scholar] [CrossRef] [PubMed]
- Duncan, T.; Valenzuela, M. Alzheimer’s disease, dementia, and stem cell therapy. Stem Cell Res. Ther. 2017, 8, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Steens, J.; Klein, D. Current strategies to generate human mesenchymal stem cells in vitro. Stem Cells Int. 2018, 2018, 24–29. [Google Scholar] [CrossRef] [PubMed]
- Wang, F.; Kong, J.; Cui, Y.-Y.; Liu, P.; Wen, J.-Y. Is human-induced pluripotent stem cell the best optimal? Chin. Med. J. 2018, 131, 852–856. [Google Scholar] [CrossRef]
- Doss, M.X.; Sachinidis, A. Current challenges of iPSC-based disease modeling and therapeutic implications. Cells 2019, 8, 403. [Google Scholar] [CrossRef] [Green Version]
- De Vos, J.; Assou, S. Induced pluripotent stem cells: An unlimited source of organs for transplantation. Clin. Res. Hepatol. Gastroenterol. 2017, 41, 249–253. [Google Scholar] [CrossRef]
- Liras, A.; Segovia, C.; Gabán, A.S. Induced pluripotent stem cells: Therapeutic applications in monogenic and metabolic diseases, and regulatory and bioethical considerations. Intech 2016, i, 13. [Google Scholar]
- Glicksman, M.A. Induced pluripotent stem cells: The most versatile source for stem cell therapy. Clin. Ther. 2018, 40, 1060–1065. [Google Scholar] [CrossRef] [Green Version]
- Rami, F.; Beni, S.N.; Kahnamooi, M.M.; Rahimmanesh, I.; Salehi, A.R.; Salehi, R. Recent advances in therapeutic applications of induced pluripotent stem cells. Cell. Reprogram. 2017, 19, 65–74. [Google Scholar] [CrossRef]
- O’Brien, F.J. Biomaterials & scaffolds for tissue engineering. Mater. Today 2011, 14, 88–95. [Google Scholar]
- De Lázaro, I.; Yilmazer, A.; Kostarelos, K. Induced pluripotent stem (iPS) cells: A new source for cell-based therapeutics? J. Control. Release 2014, 185, 37–44. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Chen, S.; Zhou, Y.; Zhao, Y.; Liu, P.; Cai, J. Application of induced pluripotent stem cell transplants: Autologous or allogeneic? Life Sci. 2018, 212, 145–149. [Google Scholar] [CrossRef] [PubMed]
- Martin, U. Therapeutic application of pluripotent stem cells: Challenges and risks. Front. Med. 2017, 4, 229. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Neofytou, E.; Brien, C.G.O.; Couture, L.A.; Wu, J.C. Hurdles to clinical translation of human induced pluripotent stem cells. 2015, 125, 2551–2557. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- de Rham, C.; Villard, J. Potential and limitation of HLA-based banking of human pluripotent stem cells for cell therapy. J. Immunol. Res. 2014, 2014, 518135. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Trounson, A.; DeWitt, N.D. Pluripotent stem cells progressing to the clinic. Nat. Rev. Mol. Cell Biol. 2016, 17, 194–200. [Google Scholar] [CrossRef]
- Mandai, M.; Watanabe, A.; Kurimoto, Y.; Hirami, Y.; Morinaga, C.; Daimon, T.; Fujihara, M.; Akimaru, H.; Sakai, N.; Shibata, Y.; et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N. Engl. J. Med. 2017, 376, 1038–1046. [Google Scholar] [CrossRef]
- Cyranoski, D. Japanese man is first to receive “reprogrammed” stem cells from another person. Nature 2017, 10. [Google Scholar] [CrossRef]
- Cyranoski, D. Woman is first to receive cornea made from “reprogrammed” stem cells. Nature 2019. [Google Scholar] [CrossRef]
- Cyranoski, D. “Reprogrammed” stem cells implanted into patient with Parkinson’s disease. Nature 2018. [Google Scholar] [CrossRef]
- Nianias, A.; Themeli, M. Induced pluripotent stem cell (iPSC)–derived lymphocytes for adoptive cell immunotherapy: Recent advances and challenges. Curr. Hematol. Malig. Rep. 2019, 261–268. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rasko, J.E.J.; Patel, A.; Griffin, J.E.; Gilleece, M.H.; Radia, R.; Yeung, D.T.; Slukvin, I.; Kelly, K.; Bloor, A.J. Results of the first completed clinical trial of an iPSC-derived product: CYP-001 in steroid-resistant acute GvHD. Biol. Blood Marrow Transplant. 2019, 25, S255–S256. [Google Scholar] [CrossRef]
- Cyranoski, D. “Reprogrammed” stem cells to treat spinal-cord injuries for the first time. Nature 2019. [Google Scholar] [CrossRef]
- Cyranoski, D. “Reprogrammed” stem cells approved to mend human hearts for the first time. Nature 2018. [Google Scholar] [CrossRef] [Green Version]
- Akabayashi, A.; Nakazawa, E.; Jecker, N.S. The world’s first clinical trial for an aplastic anemia patient with thrombocytopenia administering platelets generated from autologous iPS cells. Int. J. Hematol. 2019, 109, 239–240. [Google Scholar] [CrossRef]
- Carr, A.J.; Vugler, A.A.; Hikita, S.T.; Lawrence, J.M.; Gias, C.; Chen, L.L.; Buchholz, D.E.; Ahmado, A.; Semo, M.; Smart, M.J.K.; et al. Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS ONE 2009, 4, e8152. [Google Scholar] [CrossRef]
- Kamao, H.; Mandai, M.; Okamoto, S.; Sakai, N.; Suga, A.; Sugita, S.; Kiryu, J.; Takahashi, M. Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Rep. 2014, 2, 205–218. [Google Scholar] [CrossRef] [Green Version]
- Garber, K. RIKEN suspends first clinical trial involving induced pluripotent stem cells. Nat. Biotechnol. 2015, 33, 890–891. [Google Scholar] [CrossRef]
- Scudellari, M. A decade of iPS cells. Nature 2016, 534, 310–312. [Google Scholar] [CrossRef]
- Apatoff, M.B.L.; Sengillo, J.D.; White, E.C.; Bakhoum, M.F.; Bassuk, A.G.; Mahajan, V.B.; Tsang, S.H. Autologous stem cell therapy for inherited and acquired retinal disease. Regen. Med. 2018, 13, 89–96. [Google Scholar] [CrossRef]
- Streilein, J.W.; Ma, N.; Wenkel, H.; Fong Ng, T.; Zamiri, P. Immunobiology and privilege of neuronal retina and pigment epithelium transplants. Vision Res. 2002, 42, 487–495. [Google Scholar] [CrossRef]
- Sugita, S.; Iwasaki, Y.; Makabe, K.; Kamao, H.; Mandai, M.; Shiina, T.; Ogasawara, K.; Hirami, Y.; Kurimoto, Y.; Takahashi, M. Successful transplantation of retinal pigment epithelial cells from MHC homozygote iPSCs in MHC-matched models. Stem Cell Rep. 2016, 7, 635–648. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Umekage, M.; Sato, Y.; Takasu, N. Overview: an iPS cell stock at CiRA. Inflamm. Regen. 2019, 39, 17. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wernig, M.; Zhao, J.P.; Pruszak, J.; Hedlund, E.; Fu, D.; Soldner, F.; Broccoli, V.; Constantine-Paton, M.; Isacson, O.; Jaenisch, R. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc. Natl. Acad. Sci. USA 2008, 105, 5856–5861. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kikuchi, T.; Morizane, A.; Doi, D.; Magotani, H.; Onoe, H.; Hayashi, T.; Mizuma, H.; Takara, S.; Takahashi, R.; Inoue, H.; et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature 2017, 548, 592–596. [Google Scholar] [CrossRef] [PubMed]
- Hermanson, D.L.; Bendzick, L.; Pribyl, L.; McCullar, V.; Vogel, R.I.; Miller, J.S.; Geller, M.A.; Kaufman, D.S. Induced pluripotent stem cell-derived natural killer cells for treatment of ovarian cancer. Stem Cells 2016, 34, 93–101. [Google Scholar] [CrossRef] [Green Version]
- Ozay, E.I.; Vijayaraghavan, J.; Gonzalez-Perez, G.; Shanthalingam, S.; Sherman, H.L.; Garrigan, D.T.; Chandiran, K.; Torres, J.A.; Osborne, B.A.; Tew, G.N.; et al. CymerusTM iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease. Stem Cell Res. 2019, 35, 1–29. [Google Scholar] [CrossRef]
- Kobayashi, Y.; Okada, Y.; Itakura, G.; Iwai, H.; Nishimura, S.; Yasuda, A.; Nori, S.; Hikishima, K.; Konomi, T.; Fujiyoshi, K.; et al. Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity. PLoS ONE 2012, 7, e52787. [Google Scholar] [CrossRef] [Green Version]
- Tsuji, O.; Sugai, K.; Yamaguchi, R.; Tashiro, S.; Nagoshi, N.; Kohyama, J.; Iida, T.; Ohkubo, T.; Itakura, G.; Isoda, M.; et al. Concise review: laying the groundwork for a first-in-human study of an induced pluripotent stem cell-based intervention for spinal cord injury. Stem Cells 2019, 37, 6–13. [Google Scholar] [CrossRef] [Green Version]
- Kawamura, M.; Miyagawa, S.; Fukushima, S.; Saito, A.; Miki, K.; Funakoshi, S.; Yoshida, Y.; Yamanaka, S.; Shimizu, T.; Okano, T.; et al. Enhanced therapeutic effects of human iPS cell derived-cardiomyocyte by combined cell-sheets with omental flap technique in porcine ischemic cardiomyopathy model. Sci. Rep. 2017, 7, 1–11. [Google Scholar] [CrossRef]
- Kimbrel, E.A.; Lanza, R. Pluripotent stem cells: the last 10 years. Regen. Med. 2016, 11, 831–847. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Omole, A.E.; Fakoya, A.O.J. Ten years of progress and promise of induced pluripotent stem cells: Historical origins, characteristics, mechanisms, limitations, and potential applications. PeerJ 2018, 6, e4370. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Karagiannis, P.; Nakauchi, A.; Yamanaka, S. Bringing induced pluripotent stem cell technology to the bedside. JMA J. 2018, 1, 6–14. [Google Scholar]
- Bravery, C.A. Do human leukocyte antigen-typed cellular therapeutics based on induced pluripotent stem cells make commercial sense? Stem Cells Dev. 2015, 24, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Kimbrel, E.A.; Lanza, R. Current status of pluripotent stem cells: Moving the first therapies to the clinic. Nat. Rev. Drug Discov. 2015, 14, 681–692. [Google Scholar] [CrossRef]
- D’Antonio, M.; Woodruff, G.; Nathanson, J.L.; D’Antonio-Chronowska, A.; Arias, A.; Matsui, H.; Williams, R.; Herrera, C.; Reyna, S.M.; Yeo, G.W.; et al. High-throughput and cost-effective characterization of induced pluripotent stem cells. Stem Cell Rep. 2017, 8, 1101–1111. [Google Scholar]
- Turinetto, V.; Orlando, L.; Giachino, C. Induced pluripotent stem cells: Advances in the quest for genetic stability during reprogramming process. Int. J. Mol. Sci. 2017, 18, 1952. [Google Scholar] [CrossRef] [Green Version]
- Attwood, S.; Edel, M. iPS-cell technology and the problem of genetic instability—can it ever be safe for clinical use? J. Clin. Med. 2019, 8, 288. [Google Scholar] [CrossRef] [Green Version]
- Yoshihara, M.; Hayashizaki, Y.; Murakawa, Y. Genomic instability of iPSCs: Challenges towards their clinical applications. Stem Cell Rev. Rep. 2017, 13, 7–16. [Google Scholar] [CrossRef] [Green Version]
- Zhao, T.; Zhang, Z.-N.; Rong, Z.; Xu, Y. Immunogenicity of induced pluripotent stem cells. Nature 2011, 474, 212–215. [Google Scholar] [CrossRef] [Green Version]
- de Almeida, P.E.; Meyer, E.H.; Kooreman, N.G.; Diecke, S.; Dey, D.; Sanchez-Freire, V.; Hu, S.; Ebert, A.; Odegaard, J.; Mordwinkin, N.M.; et al. Transplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance. Nat. Commun. 2014, 5, 3903. [Google Scholar] [CrossRef] [PubMed]
- Guha, P.; Morgan, J.W.; Mostoslavsky, G.; Rodrigues, N.P.; Boyd, A.S. Lack of immune response to differentiated cells derived from syngeneic induced pluripotent stem cells. Cell Stem Cell 2017, 21, 144–148. [Google Scholar] [CrossRef] [PubMed]
- Zhao, T.; Zhang, Z.; Westenskow, P.D.; Todorova, D.; Hu, Z.; Lin, T.; Rong, Z.; Kim, J.; He, J.; Wang, M.; et al. Humanized mice reveal differential immunogenicity of cells derived from autologous induced pluripotent stem cells. Cell Stem Cell 2015, 17, 353–359. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, X.; Li, W.; Fu, X.; Xu, Y. The immunogenicity and immune tolerance of pluripotent stem cell derivatives. Front. Immunol. 2017, 8, 645. [Google Scholar] [CrossRef] [Green Version]
- Chhabra, A. Inherent immunogenicity or lack thereof of pluripotent stem cells: implications for cell replacement therapy. Front. Immunol. 2017, 8, 993. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Solomon, S.; Pitossi, F.; Rao, M.S. Banking on iPSC--is it doable and is it worthwhile. Stem Cell Rev. Rep. 2015, 11, 1–10. [Google Scholar] [CrossRef] [Green Version]
- Nakajima, F.; Tokunaga, K.; Nakatsuji, N. Human leukocyte antigen matching estimations in a hypothetical bank of human embryonic stem cell lines in the japanese population for use in cell transplantation therapy. Stem Cells 2007, 25, 983–985. [Google Scholar] [CrossRef]
- Taylor, C.J.; Peacock, S.; Chaudhry, A.N.; Bradley, J.A.; Bolton, E.M. Generating an iPSC bank for HLA-matched tissue transplantation based on known donor and recipient HLA types. Cell Stem Cell 2012, 11, 147–152. [Google Scholar] [CrossRef] [Green Version]
- Okita, K.; Matsumura, Y.; Sato, Y.; Okada, A.; Morizane, A.; Okamoto, S.; Hong, H.; Nakagawa, M.; Tanabe, K.; Tezuka, K.; et al. A more efficient method to generate integration-free human iPS cells. Nat. Methods 2011, 8, 409–412. [Google Scholar] [CrossRef] [Green Version]
- Huang, C.Y.; Liu, C.L.; Ting, C.Y.; Chiu, Y.T.; Cheng, Y.C.; Nicholson, M.W.; Hsieh, P.C.H. Human iPSC banking: Barriers and opportunities. J. Biomed. Sci. 2019, 26, 87. [Google Scholar] [CrossRef] [Green Version]
- Blackford, S.J.I.; Ng, S.S.; Segal, J.M.; King, A.J.F.; Austin, A.L.; Kent, D.; Moore, J.; Sheldon, M.; Ilic, D.; Dhawan, A.; et al. Validation of current good manufacturing practice compliant human pluripotent stem cell-derived hepatocytes for cell-based therapy. Stem Cells Transl. Med. 2019, 8, 124–137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lavon, N.; Zimerman, M.; Itskovitz-Eldor, J. Scalable expansion of pluripotent stem cells. In Advances in Biochemical Engineering/Biotechnology; Spinger: Berlin, Germany, 2018; Volume 163, pp. 23–37. [Google Scholar]
- Andrews, P.W.; Ben-David, U.; Benvenisty, N.; Coffey, P.; Eggan, K.; Knowles, B.B.; Nagy, A.; Pera, M.; Reubinoff, B.; Rugg-Gunn, P.J.; et al. Assessing the safety of human pluripotent stem cells and their derivatives for clinical applications. Stem Cell Rep. 2017, 9, 1–4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, K.; Kong, Y.; Zhang, M.; Xie, F.; Liu, P.; Xu, S. Differentiation of pluripotent stem cells for regenerative medicine. Biochem. Biophys. Res. Commun. 2016, 471, 1–4. [Google Scholar] [CrossRef] [PubMed]
- Piga, D.; Salani, S.; Magri, F.; Brusa, R.; Mauri, E.; Comi, G.P.; Bresolin, N.; Corti, S. Human induced pluripotent stem cell models for the study and treatment of Duchenne and Becker muscular dystrophies. Ther. Adv. Neurol. Disord. 2019, 12, 1–28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maffioletti, S.M.; Gerli, M.F.M.; Ragazzi, M.; Dastidar, S.; Benedetti, S.; Loperfido, M.; Vandendriessche, T.; Chuah, M.K.; Tedesco, F.S. Efficient derivation and inducible differentiation of expandable skeletal myogenic cells from human ES and patient-specific iPS cells. Nat. Protoc. 2015, 10, 941–958. [Google Scholar] [CrossRef] [PubMed]
- Chal, J.; Tanoury, Z.A.; Hestin, M.; Gobert, B.; Aivio, S.; Hick, A.; Cherrier, T.; Nesmith, A.P.; Parker, K.K.; Pourquié, O. Generation of human muscle fibers and satellite-like cells from human pluripotent stem cells in vitro. Nat. Protoc. 2016, 11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Teotia, P.; Chopra, D.A.; Dravid, S.M.; Van Hook, M.J.; Qiu, F.; Morrison, J.; Rizzino, A.; Ahmad, I. Generation of functional human retinal ganglion cells with target specificity from pluripotent stem cells by chemically defined recapitulation of developmental mechanism. Stem Cells 2017, 35, 572–585. [Google Scholar] [CrossRef] [Green Version]
- Yoshida, Y.; Yamanaka, S. Induced pluripotent stem cells 10 years later for cardiac applications. Circ. Res. 2017, 120, 1958–1968. [Google Scholar] [CrossRef]
- Penney, J.; Ralvenius, W.T.; Tsai, L.H. Modeling Alzheimer’s disease with iPSC-derived brain cells. Mol. Psychiatry 2019, 1–20. [Google Scholar] [CrossRef] [Green Version]
- Selvaraj, S.; Mondragon-Gonzalez, R.; Xu, B.; Magli, A.; Kim, H.; Lainé, J.; Kiley, J.; Mckee, H.; Rinaldi, F.; Aho, J.; et al. Screening identifies small molecules that enhance the maturation of human pluripotent stem cell-derived myotubes. Elife 2019, 8. [Google Scholar]
- Machiraju, P.; Greenway, S.C. Current methods for the maturation of induced pluripotent stem cellderived cardiomyocytes. World J. Stem Cells 2019, 11, 33–43. [Google Scholar] [CrossRef] [PubMed]
- Sułkowski, M.; Konieczny, P.; Chlebanowska, P.; Majka, M. Introduction of exogenous HSV-TK suicide gene increases safety of keratinocyte-derived induced pluripotent stem cells by providing genetic “emergency exit” switch. Int. J. Mol. Sci. 2018, 19, 197. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Deuse, T.; Hu, X.; Gravina, A.; Wang, D.; Tediashvili, G.; De, C.; Thayer, W.O.; Wahl, A.; Garcia, J.V.; Reichenspurner, H.; et al. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat. Biotechnol. 2019, 37, 252–258. [Google Scholar] [CrossRef] [PubMed]
- Shani, T.; Hanna, J.H. Universally non-immunogenic iPSCs. Nat. Biomed. Eng. 2019, 3, 337–338. [Google Scholar] [CrossRef]
Disease | Cell Type | Transplant Type | Institution and Country | Study Start Date * | Registration Number | Status | Reference |
---|---|---|---|---|---|---|---|
Age-related macular degeneration | Retinal pigment epithelial cells | Autologous | RIKEN Centre for Developmental Biology (Japan) | October 2013 | UMIN000011929 | Phase I (suspended) | [47] |
Age-related macular degeneration | Retinal pigment epithelial cells | Allogeneic | RIKEN Centre for Developmental Biology (Japan) | Unknown | Unknown | Phase I | [48] |
Limbal stem cell deficiency | Corneal stem cells | Allogeneic | Osaka University (Japan) | Unknown | Unknown | Phase I | [49] |
Parkinson | Dopamine precursor cells | Allogeneic | Kyoto University (Japan) | July 2018 | UMIN000033564 | Phase I/II | [50] |
Cancer | Natural killer cells | Allogeneic | University of Minnesota (US) and Fate Therapeutics (US) | February 2019 | NCT03841110 | Phase I | [51] |
Graft-versus-host disease | Mesenchymal stem cells | Allogeneic | Cynata Therapeutics (Australia) | October 2016 | NCT02923375 | Phase I completed | [52] |
Spinal cord injury | Neural progenitor cells | Allogeneic | Keio University (Japan) | N/A | N/A | Not yet recruiting | [53] |
Heart failure | Cardiomyocytes | Allogeneic | Osaka University (Japan) | June 2018 | UMIN000032989 | Not yet recruiting | [54] |
Aplastic anemia | Platelets | Autologous | Kyoto University (Japan) | N/A | N/A | Not yet recruiting | [55] |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ortuño-Costela, M.d.C.; Cerrada, V.; García-López, M.; Gallardo, M.E. The Challenge of Bringing iPSCs to the Patient. Int. J. Mol. Sci. 2019, 20, 6305. https://doi.org/10.3390/ijms20246305
Ortuño-Costela MdC, Cerrada V, García-López M, Gallardo ME. The Challenge of Bringing iPSCs to the Patient. International Journal of Molecular Sciences. 2019; 20(24):6305. https://doi.org/10.3390/ijms20246305
Chicago/Turabian StyleOrtuño-Costela, María del Carmen, Victoria Cerrada, Marta García-López, and M. Esther Gallardo. 2019. "The Challenge of Bringing iPSCs to the Patient" International Journal of Molecular Sciences 20, no. 24: 6305. https://doi.org/10.3390/ijms20246305