Skip to main content

Advertisement

SpringerLink
Log in

Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation

  • Review
  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

Ten years have passed since the first publication announcing the generation of induced pluripotent stem cells (iPSCs). Issues related to ethics, immune rejection, and cell availability seemed to be solved following this breakthrough. The development of iPSC technology allows advances in in vitro cell differentiation for cell therapy purpose and other clinical applications. This review provides a perspective on the iPSC potential for cell therapies, particularly for hematological applications. We discuss the advances in in vitro hematopoietic differentiation, the possibilities to employ iPSC in hematology studies, and their potential clinical application in hematologic diseases. The generation of red blood cells and functional T cells and the genome editing technology applied to mutation correction are also covered. We highlight some of the requirements and obstacles to be overcome before translating these cells from research to the clinic, for instance, iPSC variability, genotoxicity, the differentiation process, and engraftment. Also, we evaluate the patent landscape and compile the clinical trials in the field of pluripotent stem cells. Currently, we know much more about iPSC than in 2006, but there are still challenges that must be solved. A greater understanding of molecular mechanisms underlying the generation of hematopoietic stem cells is necessary to produce suitable and transplantable hematopoietic stem progenitor cells from iPSC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Notes

  1. Hematopoietic differentiation dataset search query: “TAC: (((haematopoietic ADJ different*) OR (hematopoietic ADJ cell* ADJ induc*) OR (differentia* NEAR7 hemocytoblast) OR ((differentia* NEAR7 (myeloid ADJ cell*)) OR ((differentia* NEAR7 (lymphoid ADJ cell*)) OR ((Produc* OR generat*) NEAR3 Hematopoietic ADJ Cell*)) OR ((Produc* OR Generat*) NEAR3 blood ADJ Cell*)) OR (hematopoietic ADJ cell* different*) OR (induc* NEAR4 (Hematopoietic ADJ cell*)) OR (Differenti* NEAR2 cell* NEAR2 blood) OR (Blood ADJ cell* ADJ different*) OR ((Different* OR Programm*) NEAR12 (hematopoietic ADJ cell*)) OR ((Different* OR Program*) NEAR12 (blood)) OR ((different* OR program*) NEAR12 (blood ADJ Cell*)) OR (Different* NEAR3 (bone ADJ marrow ADJ Cell*)))).”

References

  • Abed S, Tubsuwan A, Chaichompoo P, Park IH, Pailleret A, Benyoucef A, et al. Transplantation of Macaca cynomolgus iPS-derived hematopoietic cells in NSG immunodeficient mice. Haematologica. 2015;100(10):e428–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Agarwal S, Loh Y-H, McLoughlin EM, Huang J, Park I-H, Miller JD, et al. Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature. 2010;464(7286):292–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amabile G, Welner RS, Nombela-Arrieta C, D’Alise AM, Di Ruscio A, Ebralidze AK, et al. In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells. Blood. 2013;121(8):1255–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Araki R, Uda M, Hoki Y, Sunayama M, Nakamura M, Ando S, et al. Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature. 2013;494(7435):100–4.

    Article  CAS  PubMed  Google Scholar 

  • Avior Y, Sagi I, Benvenisty N. Pluripotent stem cells in disease modelling and drug discovery. Nat Rev Mol Cell Biol. 2016;17(3):170–82.

    Article  CAS  PubMed  Google Scholar 

  • Baghbaderani BA, Tian X, Neo BH, Burkall A, Dimezzo T, Sierra G, et al. cGMP-manufactured human induced pluripotent stem cells are available for pre-clinical and clinical applications. Stem Cell Reports. 2015;5(4):647–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bedel A, Pasquet JM, Lippert É, Taillepierre M, Lagarde V, Dabernat S, et al. 2013 Variable behavior of iPSCs derived from CML patients for response to TKI and hematopoietic differentiation. Eaves CJ, (ed). PLoS One. 8(8):e71596.

  • Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science. 2009;326(5959):1509–12.

    Article  CAS  PubMed  Google Scholar 

  • Braam SR, Tertoolen L, van de Stolpe A, Meyer T, Passier R, Mummery CL. Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes. Stem Cell Res. 2010;4(2):107–16.

    Article  CAS  PubMed  Google Scholar 

  • Briquet A, Dubois S, Bekaert S, Dolhet M, Beguin Y, Gothot A. Prolonged ex vivo culture of human bone marrow mesenchymal stem cells influences their supportive activity toward NOD/SCID-repopulating cells and committed progenitor cells of B lymphoid and myeloid lineages. Haematologica. 2010;95(1):47–56.

    Article  PubMed  Google Scholar 

  • Brown ME, Rondon E, Rajesh D, Mack A, Lewis R, Feng X, et al. 2010 Derivation of induced pluripotent stem cells from human peripheral blood T lymphocytes. Unutmaz D, (ed.) PLoS One. 5(6):e11373.

  • Cerdan C, McIntyre BAS, Mechael R, Levadoux-Martin M, Yang J, Lee JB, et al. Activin a promotes hematopoietic fated mesoderm development through upregulation of brachyury in human embryonic stem cells. Stem Cells Dev. 2012;21(15):2866–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cherry ABC, Gagne KE, Mcloughlin EM, Baccei A, Gorman B, Hartung O, et al. Induced pluripotent stem cells with a mitochondrial DNA deletion. Stem Cells. 2013;31(7):1287–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chou B-K, Mali P, Huang X, Ye Z, Dowey SN, Resar LM, et al. Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. Cell Res. 2011;21(3):518–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Connelly JP, Kwon EM, Gao Y, Trivedi NS, Elkahloun AG, Horwitz MS, et al. Targeted correction of RUNX1 mutation in FPD patient-specific induced pluripotent stem cells rescues megakaryopoietic defects. Blood. 2014;124(12):1926–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dorn I, Klich K, Arauzo-Bravo MJ, Radstaak M, Santourlidis S, Ghanjati F, et al. Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin. Haematologica. 2015;100(1):32–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dowey SN, Huang X, Chou B-K, Ye Z, Cheng L. Generation of integration-free human induced pluripotent stem cells from postnatal blood mononuclear cells by plasmid vector expression. Nat Protoc. 2012;7(11):2013–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Escobedo-Cousin M, Jackson N, Laza-Briviesca R, Ariza-McNaughton, L, Luevano M, Derniame S, et al. 2015 Natural killer cells improve hematopoietic stem cell engraftment by increasing stem cell clonogenicity In: Rameshwar P, (ed.) Vitro and in a humanized mouse model. PLoS One. 10(10):e0138623.

  • Fernández-García M, Yañez RM, Sánchez-Domínguez R, Hernando-Rodriguez M, Peces-Barba M, Herrera G, et al. Mesenchymal stromal cells enhance the engraftment of hematopoietic stem cells in an autologous mouse transplantation model. Stem Cell Res Ther. 2015;6(1):165.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fujita A, Uchida N, Haro-Mora JJ, Winkler T, Tisdale J. β-Globin-expressing definitive erythroid progenitor cells generated from embryonic and induced pluripotent stem cell-derived sacs. Stem Cells. 2016;34(6):1541–52.

    Article  CAS  PubMed  Google Scholar 

  • Gaj T, Gersbach CA, Barbas CFZFN. TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31(7):397–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gandre-Babbe S, Paluru P, Aribeana C, Chou ST, Bresolin S, Lu L, et al. Patient-derived induced pluripotent stem cells recapitulate hematopoietic abnormalities of juvenile myelomonocytic leukemia. Blood. 2013;121(24):4925–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garber KRIKEN. Suspends first clinical trial involving induced pluripotent stem cells. Nat Biotechnol Nature Research. 2015;33(9):890–1.

    Article  CAS  Google Scholar 

  • Garçon L, Ge J, Manjunath SH, Mills JA, Apicella M, Parikh S, et al. Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients. Blood. 2013;122(6):912–21.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ge J, Apicella M, Mills JA, Garçon L, French DL, Weiss MJ, et al. 2015 Dysregulation of the transforming growth factor β pathway in Induced pluripotent stem cells generated from patients with Diamond Blackfan anemia. Freeman J, (ed.). PLoS One. 10(8):e0134878.

  • Goh PA, Caxaria S, Casper C, Rosales C, Warner TT, Coffey PJ, et al.. 2013 A systematic evaluation of integration free reprogramming methods for deriving clinically relevant patient specific induced pluripotent stem (iPS) cells. Wilber AC, (ed). PLoS One. Public Library of Science 8(11):e81622.

  • Goldring CEP, Duffy PA, Benvenisty N, Andrews PW, Ben-David U, Eakins R, et al. Assessing the safety of stem cell therapeutics. Cell Stem Cell. 2011;8(6):618–28.

    Article  CAS  PubMed  Google Scholar 

  • Gori JL, Butler JM, Chan Y-Y, Chandrasekaran D, Poulos MG, Ginsberg M, et al. Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells. J Clin Invest. 2015;125(3):1243–54.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gu B, Mills JA, Apicella M, Fan J, French DL, Bessler M, et al. Phenotypic rescue of induced pluripotent stem cells from dyskeratosis congenita patients by ectopic expression of DKC1 but not TERC. Blood. 2013;122(21)

  • Hafez M, Hausner G, Bonen L. Homing endonucleases: DNA scissors on a mission. Genome. 2012;55(8):553–69.

    Article  CAS  PubMed  Google Scholar 

  • Hermanson DL, Bendzick L, Pribyl L, McCullar V, Vogel RI, Miller JS, et al. Induced pluripotent stem cell-derived natural killer cells for treatment of ovarian cancer. Stem Cells. 2016;34(1):93–101.

    Article  CAS  PubMed  Google Scholar 

  • Hirata S, Takayama N, Jono-Ohnishi R, Endo H, Nakamura S, Dohda T, et al. Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling. J Clin Invest. 2013;123(9):3802–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hong SG, Dunbar CE, Winkler T. Assessing the risks of genotoxicity in the therapeutic development of induced pluripotent stem cells. Mol Ther. 2013;21(2):272–81.

    Article  CAS  PubMed  Google Scholar 

  • Hosoi M, Kumano K, Taoka K, Arai S, Kataoka K, Ueda K, et al. Generation of induced pluripotent stem cells derived from primary and secondary myelofibrosis patient samples. ISEH—International Society for Experimental Hematology. 2014;42(9):816–25. doi:10.1016/j.exphem.2014.03.010.

  • Huang X, Wang Y, Yan W, Smith C, Ye Z, Wang J, et al. Production of gene-corrected adult beta globin protein in human erythrocytes differentiated from patient iPSCs after genome editing of the sickle point mutation. Stem Cells. 2015;33(5):1470–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iizuka H, Kagoya Y, Kataoka K, Yoshimi A, Miyauchi M, Taoka K, et al. Targeted gene correction of RUNX1 in induced pluripotent stem cells derived from familial platelet disorder with propensity to myeloid malignancy restores normal megakaryopoiesis. ISEH—International Society for Experimental Hematology. 2015;43(10):849–57.

    Article  CAS  Google Scholar 

  • Izawa K, Kakegawa T, Yamamoto M, Tojo A. Forced HoxB4 sustains CD45-c-kit+ pre-hematopoietic stem cells (HSCs) derived from murine induced-pluripotent stem cells, which develop long-term and short-term repopulating HSCs according to GATA2 expression level. Blood. 2014;124(21)

  • Jia B, Chen S, Zhao Z, Liu P, Cai J, Qin D, et al. Modeling of hemophilia A using patient-specific induced pluripotent stem cells derived from urine cells. Life Sci. 2014;108(1):22–9.

    Article  CAS  PubMed  Google Scholar 

  • Kang X, Yu Q, Huang Y, Song B, Chen Y, Gao X, et al. Effects of integrating and non-integrating reprogramming methods on copy number variation and genomic stability of human induced pluripotent stem cells. Johnson R, editor. PLoS One 2015 10(7):e0131128.

  • Kappler-Gratias S, Peyrard T, Beolet M, Amiranoff D, Menanteau C, Dubeaux I, et al. Blood group genotyping by high-throughput DNA analysis applied to 356 reagent red blood cell samples. Transfusion. 2011;51(1):36–42.

    Article  CAS  PubMed  Google Scholar 

  • Kaufman DS, Hanson ET, Lewis RL, Auerbach R, Thomson JA. Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc Natl Acad Sci. 2001;98(19):10716–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keller G, Kennedy M, Papayannopoulou T, Wiles MV. Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol. 1993;13(1):473–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kennedy M, Awong G, Sturgeon CM, Ditadi A, LaMotte-Mohs R, Zúñiga-Pflücker JC, et al. T lymphocyte potential marks the emergence of definitive hematopoietic progenitors in human pluripotent stem cell differentiation cultures. Cell Rep. 2012;2(6):1722–35.

    Article  CAS  PubMed  Google Scholar 

  • Koyanagi-Aoi M, Ohnuki M, Takahashi K, Okita K, Noma H, Sawamura Y, et al. Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells. Proc Natl Acad Sci. 2013;110(51):20569–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumano K, Arai S, Hosoi M, Taoka K, Takayama N, Otsu M, et al. Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples. Blood. 2012;119(26):6234–42.

    Article  CAS  PubMed  Google Scholar 

  • Lacaud G. Runx1 is essential for hematopoietic commitment at the hemangioblast stage of development in vitro. Blood. 2002;100(2):458–66.

    Article  CAS  PubMed  Google Scholar 

  • Lapillonne H, Kobari L, Mazurier C, Tropel P, Giarratana MC, Zanella-Cleon I, et al. Red blood cell generation from human induced pluripotent stem cells: perspectives for transfusion medicine. Haematologica. 2010;95(10):1651–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lengerke C, Grauer M, Niebuhr NI, Riedt T, Kanz L, Park I-H, et al. Hematopoietic development from human induced pluripotent stem cells. Ann N Y Acad Sci. 2009;1176(1):219–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang HC-Y, Holmes R, Zúñiga-Pflücker JC. Directed differentiation of embryonic stem cells to the T-lymphocyte lineage. Methods Mol Biol. 2013:119–28.

  • Liu J, Brzeszczynska J, Samuel K, Black J, Palakkan A, Anderson RA, et al. Efficient episomal reprogramming of blood mononuclear cells and differentiation to hepatocytes with functional drug metabolism. Exp Cell Res Elsevier. 2015;338(2):203–13.

    Article  CAS  Google Scholar 

  • Liu X, Wu M, Peng Y, Chen X, Sun J, Huang F, et al. Improvement in poor graft function after allogeneic hematopoietic stem cell transplantation upon administration of mesenchymal stem cells from third-party donors: a pilot prospective study. Cell Transplant. 2014;23(9):1087–98.

    Article  PubMed  Google Scholar 

  • Loh Y-H, Agarwal S, Park I-H, Urbach A, Huo H, Heffner GC, et al. Generation of induced pluripotent stem cells from human blood. Blood. 2009;113(22):5476–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loh Y-H, Hartung O, Li H, Guo C, Sahalie JM, Manos PD, et al. Reprogramming of T cells from human peripheral blood. Cell Stem Cell. 2010;7(1):15–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma N, Liao B, Zhang H, Wang L, Shan Y, Xue Y, et al. Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free-thalassemia induced pluripotent stem cells. J Biol Chem. 2013;288(48):34671–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mack AA, Kroboth S, Rajesh D, Wang WB. 2011 Generation of induced pluripotent stem cells from CD34+ cells across blood drawn from multiple donors with non-integrating episomal vectors. Borlongan C V., (ed.) PLoS One. 6(11):e27956.

  • Mathews DJH, Cook-Deegan R, Bubela T. Patents and misplaced angst: lessons for translational stem cell research from genomics. Cell Stem Cell. 2013;12(5):508–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minami E, Murry CE. Response to “comment on ‘transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response’”. FASEB J. 2007;21(7):1291–1.

  • Morishima T, Watanabe K -i, Niwa A, Hirai H, Saida S, Tanaka T, et al. Genetic correction of HAX1 in induced pluripotent stem cells from a patient with severe congenital neutropenia improves defective granulopoiesis. Haematologica. 2014;99(1):19–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mulero-Navarro S, Sevilla A, Roman AC, Lee D-F, D’Souza SL, Pardo S, et al. Myeloid dysregulation in a human induced pluripotent stem cell model of PTPN11-associated juvenile myelomonocytic leukemia. Cell Rep. 2015;13(3):504–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagawa M, Taniguchi Y, Senda S, Takizawa N, Ichisaka T, Asano K, et al. A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells. Sci Rep. 2014;4(3594)

  • Nayak RC, Trump LR, Aronow BJ, Myers K, Mehta P, Kalfa T, et al. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells. J Clin Invest. 2015;125(8):3103–16.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ng ES, Davis RP, Azzola L, Stanley EG, Elefanty AG. Forced aggregation of defined numbers of human embryonic stem cells into embryoid bodies fosters robust, reproducible hematopoietic differentiation. Blood. 2005;106(5):1601–3.

    Article  CAS  PubMed  Google Scholar 

  • Ng ES, Davis RP, Hatzistavrou T, Stanley EG, Elefanty AG. . 2008. Directed differentiation of human embryonic stem cells as spin embryoid bodies and a description of the hematopoietic blast colony forming assay. Curr. Protoc. Stem Cell Biol. Hoboken, NJ, USA: Wiley

  • Nishizawa M, Chonabayashi K, Nomura M, Tanaka A, Nakamura M, Inagaki A, et al. Epigenetic variation between human induced pluripotent stem cell lines is an indicator of differentiation capacity. Cell Stem Cell. 2016;19(3):341–54.

    Article  CAS  PubMed  Google Scholar 

  • Niu X, He W, Song B, Ou Z, Fan D, Chen Y, et al. Combining single strand oligodeoxynucleotides and CRISPR/Cas9 to correct gene mutations in β-thalassemia-induced pluripotent stem cells. J Biol Chem. 2016;291(32):16576–85.

    Article  CAS  PubMed  Google Scholar 

  • Ohmine S, Dietz AB, Deeds MC, Hartjes KA, Miller DR, Thatava T, et al. Induced pluripotent stem cells from GMP-grade hematopoietic progenitor cells and mononuclear myeloid cells. Stem Cell Res. Ther. 2011;2(6):46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olivier EN, Qiu C, Velho M, Hirsch RE, Bouhassira EE. Large-scale production of embryonic red blood cells from human embryonic stem cells. Exp Hematol. 2006;34(12):1635–42.

    Article  CAS  PubMed  Google Scholar 

  • Park C-Y, Kim DH, Son JS, Sung JJ, Lee J, Bae S, et al. Functional correction of large factor VIII gene chromosomal inversions in hemophilia A patient-derived iPSCs using CRISPR-Cas9. Cell Stem Cell Elsevier Inc. 2015;17(2):213–20.

    Article  CAS  Google Scholar 

  • Peyrard T, Bardiaux L, Krause C, Kobari L, Lapillonne H, Andreu G, et al. Banking of pluripotent adult stem cells as an unlimited source for red blood cell production: potential applications for alloimmunized patients and rare blood challenges. Transfus Med Rev. 2011;25(3):206–16.

    Article  PubMed  Google Scholar 

  • Pick M, Azzola L, Osborne E, Stanley EG, Elefanty AG. Generation of megakaryocytic progenitors from human embryonic stem cells in a feeder- and serum-free medium. Zambidis ET, editor. PLoS One 2013 8(2):e55530.

  • Pineault N, Robert A, Cortin V, Boyer L. Ex vivo differentiation of cord blood stem cells into megakaryocytes and platelets. Methods Mol Biol. 2013:205–24.

  • Priest CA, Manley NC, Denham J, Wirth ED, Lebkowski JS. Preclinical safety of human embryonic stem cell-derived oligodendrocyte progenitors supporting clinical trials in spinal cord injury. Regen Med. 2015;10(8):939–58.

    Article  CAS  PubMed  Google Scholar 

  • Ramos-Mejía V, Montes R, Bueno C, Ayllón V, Real PJ, Rodríguez R, et al. Residual expression of the reprogramming factors prevents differentiation of iPSC generated from human fibroblasts and cord blood CD34+ progenitors. Panepucci RA, editor. PLoS One 2012 7(4):e35824.

  • Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013;8(11):2281–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rao MS. LULL(ed) into complacency: a perspective on licenses and stem cell translational science. Stem Cell Res. Ther. 2013;4(4):98.

    PubMed  PubMed Central  Google Scholar 

  • Raya Á, Rodríguez-Pizà I, Guenechea G, Vassena R, Navarro S, Barrero MJ, et al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature. 2009;460(7251):53–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • RIKEN-Foundation for Biomedical Research and Innovation. Pilot safety study of iPSC-based intervention for wet-type AMD [Internet]. RIKEN-IBRI. 2013 [cited 2016 Sep 9]. Available from: http://www.riken-ibri.jp/AMD/english/research/index.html

  • Roberts M, Wall IB, Bingham I, Icely D, Reeve B, Bure K, et al. The global intellectual property landscape of induced pluripotent stem cell technologies. Nat Biotechnol. 2014;32(8):742–8.

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues GMC, Rodrigues CAV, Fernandes TG, Diogo MM, Cabral JMS. Clinical-scale purification of pluripotent stem cell derivatives for cell-based therapies. Biotechnol J. 2015;10(8):1103–14.

    Article  CAS  PubMed  Google Scholar 

  • Rowe RG, Mandelbaum J, Zon LI, Daley GQ. Engineering hematopoietic stem cells: lessons from development. Cell Stem Cell. 2016;18(6):707–20.

    Article  CAS  PubMed  Google Scholar 

  • Sakurai M, Kunimoto H, Watanabe N, Fukuchi Y, Yuasa S, Yamazaki S, et al. Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem cells derived from FPD/AML patients. Leukemia. 2014;28(12):2344–54.

    Article  CAS  PubMed  Google Scholar 

  • Sayed N, Liu C, Wu JC. Translation of human-induced pluripotent stem cells. J Am Coll Cardiol. 2016;67(18):2161–76.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schlaeger TM, Daheron L, Brickler TR, Entwisle S, Chan K, Cianci A, et al. A comparison of non-integrating reprogramming methods. Nat Biotechnol. 2014;33(1):58–63.

    Article  PubMed  PubMed Central  Google Scholar 

  • Scott CT. The zinc finger nuclease monopoly. Nat Biotechnol. 2005;23(8):915–8.

    Article  CAS  PubMed  Google Scholar 

  • Sebastiano V, Maeder ML, Angstman JF, Haddad B, Khayter C, Yeo DT, et al. Situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases. Stem Cells. 2011;29(11):1717–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simonson OE, Domogatskaya A, Volchkov P, Rodin S. The safety of human pluripotent stem cells in clinical treatment. Ann Med. 2015;47(5):370–80.

    Article  PubMed  Google Scholar 

  • Song B, Fan Y, He W, Zhu D, Niu X, Wang D, et al. Improved hematopoietic differentiation efficiency of gene-corrected beta-thalassemia induced pluripotent stem cells by CRISPR/Cas9 system. Stem Cells Dev. 2015;24(9):1053–65.

    Article  CAS  PubMed  Google Scholar 

  • Staerk J, Dawlaty MM, Gao Q, Maetzel D, Hanna J, Sommer CA, et al. Reprogramming of human peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell. 2010;7(1):20–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stephenson E, Jacquet L, Miere C, Wood V, Kadeva N, Cornwell G, et al. Derivation and propagation of human embryonic stem cell lines from frozen embryos in an animal product–free environment. Nat Protoc. 2012;7(7):1366–81.

    Article  CAS  PubMed  Google Scholar 

  • Sternberg SH, LaFrance B, Kaplan M, Doudna JA. Conformational control of DNA target cleavage by CRISPR–Cas9. Nature. 2015;527(7576):110–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suknuntha K, Ishii Y, Tao L, Hu K, McIntosh BE, Yang D, et al. Discovery of survival factor for primitive chronic myeloid leukemia cells using induced pluripotent stem cells. Stem Cell Res. 2015;15(3):678–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun N, Zhao H. Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs. Biotechnol Bioeng. 2014;111(5):1048–53.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki N, Yamazaki S, Yamaguchi T, Okabe M, Masaki H, Takaki S, et al. Generation of engraftable hematopoietic stem cells from induced pluripotent stem cells by way of teratoma formation. Mol Ther. 2013;21(7):1424–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taapken SM, Nisler BS, Newton MA, Sampsell-Barron TL, Leonhard KA, McIntire EM, et al. Karyotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells. Nat. Biotechnol. Nature Research. 2011;29(4):313–4.

    Article  CAS  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    Article  CAS  PubMed  Google Scholar 

  • Takayama N, Nishikii H, Usui J, Tsukui H, Sawaguchi A, Hiroyama T, et al. Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors. Blood. 2008;111(11):5298–306.

    Article  CAS  PubMed  Google Scholar 

  • Themeli M, Kloss CC, Ciriello G, Fedorov VD, Perna F, Gonen M, et al. Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy. Nat Biotechnol. 2013;31(10):928–33.

    Article  CAS  PubMed  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145–7.

    Article  CAS  PubMed  Google Scholar 

  • Timmermans F, Velghe I, Vanwalleghem L, De Smedt M, Van Coppernolle S, Taghon T, et al. Generation of T cells from human embryonic stem cell-derived hematopoietic zones. J Immunol. 2009;182(11):6879–88.

    Article  CAS  PubMed  Google Scholar 

  • Todorova D, Kim J, Hamzeinejad S, He J, Brief Report XY. Immune microenvironment determines the immunogenicity of induced pluripotent stem cell derivatives. Stem Cells. 2016;34(2):510–5.

    Article  CAS  PubMed  Google Scholar 

  • Tulpule A, Kelley JM, Lensch MW, McPherson J, Park IH, Hartung O, et al. Pluripotent stem cell models of Shwachman-Diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction. Cell Stem Cell. 2013;12(6):727–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • U. S. Food and Drug Administration. FDA warns about stem cell claims [Internet]. FDA.gov. 2012 [cited 2016 Jul 13]. Available from: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm286155.htm

  • U. S. Food and Drug Administration. Facts about the current good manufacturing practices (CGMPs) [Internet]. FDA.gov. 2015 [cited 2016 Jul 13]. Available from: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm169105.htm

  • Ugwu N, Awodu O, Bazuaye G, Okoye A. Red cell alloimmunization in multi-transfused patients with sickle cell anemia in Benin City, Nigeria. Niger J Clin Pract. 2015;18(4):522.

    Article  CAS  PubMed  Google Scholar 

  • University hospital Medical Information Network (UMIN) Center. UMIN-CTR Clinical Trial [Internet]. UMIN. 2016 [cited 2016 Sep 9]. Available from: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000013279&language=E

  • Vanhee S, De Mulder K, Van Caeneghem Y, Verstichel G, Van Roy N, Menten B, et al. Vitro human embryonic stem cell hematopoiesis mimics MYB-independent yolk sac hematopoiesis. Haematologica. 2015;100(2):157–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vizcardo R, Masuda K, Yamada D, Ikawa T, Shimizu K, Fujii S, et al. Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8+ T cells. Cell Stem Cell. 2013;12(1):31–6.

    Article  CAS  PubMed  Google Scholar 

  • Vodyanik MA. Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential. Blood. 2005;105(2):617–26.

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Chou B-K, Dowey S, He C, Gerecht S, Cheng L. Scalable expansion of human induced pluripotent stem cells in the defined xeno-free E8 medium under adherent and suspension culture conditions. Stem Cell Res. 2013;11(3):1103–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie F, Ye L, Chang JC, Beyer AI, Wang J, Muench MO, et al. Seamless gene correction of β-thalassemia mutations in patient-specific iPSCs using CRISPR/Cas9 and piggyBac. Genome Res. 2014;24(9):1526–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yazdanbakhsh K, Ware RE, Noizat-Pirenne F. Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management. Blood. 2012;120(3):528–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye L, Chang JC, Lin C, Sun X, Yu J, Kan YW. Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases. Proc Natl Acad Sci. 2009a Jun 16;106(24):9826–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye Z, Zhan H, Mali P, Dowey S, Williams DM, Jang Y-Y, et al. Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood. 2009b;114(27):5473–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20.

    Article  CAS  PubMed  Google Scholar 

  • Zhao K, Liu Q. The clinical application of mesenchymal stromal cells in hematopoietic stem cell transplantation. J Hematol Oncol. 2016;9(1):46.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work is supported in part by São Paulo Research Foundation (FAPESP), grant nos. 13/08135-2, 14/22500-8, 16/08373-9, and 16/08374-5. We would like to thank Sandra Navarro for drawing the figures.

Author information

Authors and Affiliations

  1. Ribeirão Preto Medical School and Center for Cell-based Therapy (CTC), University of São Paulo, São Paulo, Brazil

    Bárbara Cristina Martins Fernandes Paes, Pablo Diego Moço & Dimas Tadeu Covas

  2. Regional Blood Center of Ribeirão Preto, Rua Tenente Catão Roxo, 2501, Ribeirão Preto, São Paulo, 14051-140, Brazil

    Bárbara Cristina Martins Fernandes Paes, Pablo Diego Moço, Elisa Maria de Sousa Russo, Luiza Cunha Junqueira Reis, Dimas Tadeu Covas & Virginia Picanço-Castro

  3. Ribeirão Preto Pharmaceutical Sciences School, University of São Paulo, São Paulo, Brazil

    Elisa Maria de Sousa Russo & Luiza Cunha Junqueira Reis

  4. School of Economics, Business Administration and Accounting at Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    Cristiano Gonçalves Pereira & Geciane Silveira Porto

Authors
  1. Bárbara Cristina Martins Fernandes Paes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pablo Diego Moço
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cristiano Gonçalves Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Geciane Silveira Porto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elisa Maria de Sousa Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luiza Cunha Junqueira Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dimas Tadeu Covas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Virginia Picanço-Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Virginia Picanço-Castro.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Paes, B.C.M.F., Moço, P.D., Pereira, C.G. et al. Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation. Cell Biol Toxicol 33, 233–250 (2017). https://doi.org/10.1007/s10565-016-9377-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-016-9377-2

Keywords

Search

Navigation