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Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation
Authors:Bárbara Cristina Martins Fernandes Paes  Pablo Diego Moço  Cristiano Gonçalves Pereira  Geciane Silveira Porto  Elisa Maria de Sousa Russo  Luiza Cunha Junqueira Reis  Dimas Tadeu Covas  Virginia Picanço-Castro
Institution:1.Ribeir?o Preto Medical School and Center for Cell-based Therapy (CTC),University of S?o Paulo,S?o Paulo,Brazil;2.Regional Blood Center of Ribeir?o Preto,S?o Paulo,Brazil;3.Ribeir?o Preto Pharmaceutical Sciences School,University of S?o Paulo,S?o Paulo,Brazil;4.School of Economics, Business Administration and Accounting at Ribeir?o Preto,University of S?o Paulo,S?o Paulo,Brazil
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.
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