title: Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation.
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.
authors.affiliation: Ribeirão Preto Medical School and Center for Cell-based Therapy (CTC), University of São Paulo, São Paulo, Brazil.|Regional Blood Center of Ribeirão Preto, Rua Tenente Catão Roxo, 2501, Ribeirão Preto, São Paulo, 14051-140, Brazil.
authors.forename: Bárbara Cristina Martins Fernandes
authors.initials: BCMF
authors.lastname: Paes
authors.affiliation: Ribeirão Preto Medical School and Center for Cell-based Therapy (CTC), University of São Paulo, São Paulo, Brazil.|Regional Blood Center of Ribeirão Preto, Rua Tenente Catão Roxo, 2501, Ribeirão Preto, São Paulo, 14051-140, Brazil.
authors.forename: Pablo Diego
authors.initials: PD
authors.lastname: Moço
authors.affiliation: School of Economics, Business Administration and Accounting at Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Cristiano Gonçalves
authors.initials: CG
authors.lastname: Pereira
authors.affiliation: School of Economics, Business Administration and Accounting at Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Geciane Silveira
authors.initials: GS
authors.lastname: Porto
authors.affiliation: Regional Blood Center of Ribeirão Preto, Rua Tenente Catão Roxo, 2501, Ribeirão Preto, São Paulo, 14051-140, Brazil.|Ribeirão Preto Pharmaceutical Sciences School, University of São Paulo, São Paulo, Brazil.
authors.forename: Elisa Maria
authors.initials: EM
authors.lastname: de Sousa Russo
authors.affiliation: Regional Blood Center of Ribeirão Preto, Rua Tenente Catão Roxo, 2501, Ribeirão Preto, São Paulo, 14051-140, Brazil.|Ribeirão Preto Pharmaceutical Sciences School, University of São Paulo, São Paulo, Brazil.
authors.forename: Luiza Cunha Junqueira
authors.initials: LCJ
authors.lastname: Reis
authors.affiliation: Ribeirão Preto Medical School and Center for Cell-based Therapy (CTC), University of São Paulo, São Paulo, Brazil.|Regional Blood Center of Ribeirão Preto, Rua Tenente Catão Roxo, 2501, Ribeirão Preto, São Paulo, 14051-140, Brazil.
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.affiliation: Regional Blood Center of Ribeirão Preto, Rua Tenente Catão Roxo, 2501, Ribeirão Preto, São Paulo, 14051-140, Brazil. virginia.picanco@hemocentro.fmrp.usp.br.
authors.forename: Virginia
authors.initials: V
authors.lastname: Picanço-Castro
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*
keywords: Blood cells; Clinical trials; Hematopoietic differentiation; Induced pluripotent stem cells; Patent landscape