title: Direct Conversion Through Trans-Differentiation: Efficacy and Safety.
abstract: Direct conversion through transdifferentiation is a promising cell reprogramming approach that induces a cell lineage conversion among adult cells without passing through an intermediate pluripotent phase. However, there is a need to critically evaluate the efficacy and safety of direct conversion to establish its feasibility as a clinically viable cell reprogramming technique. This review article aims to delineate some critical constraints of direct conversion as a cellular reprogramming approach. We report the most important challenges of lineage reprogramming through direct conversion and divide them into two major sections. The first section explores the obstacles that limit the efficiency of the direct conversion process. In this study, we discuss challenges such as lack of understanding of molecular mechanism and transcriptional control of direct conversion, low proliferative capacity of converted cells, and senescence and apoptosis as critical barriers of direct conversion. The second section focuses on addressing concerns of safety of directly converted cells. We describe issues of transgene load and epigenetic memory retention along with the constraints of currently available validation tools to characterize reprogrammed cells. Each issue mentioned above is evaluated in view of their origin, implications, progress made toward their resolution and scope for development of new strategies to address the constraints of the present technique.
authors: 1 Department of Biomedical Engineering, National University of Singapore , Singapore, Singapore .
authors: Ankshita
authors: A
authors: Prasad
authors: Department of Singapore Institute of Neurotechnology, National University of Singapore , Singapore, Singapore .
authors: Daniel Boon Loong
authors: DB
authors: Teh
authors: Department of Orthopaedic Surgery, National University of Singapore , Singapore, Singapore .
authors: Fathima R
authors: FR
authors: Shah Jahan
authors: Department of Orthopaedic Surgery, National University of Singapore , Singapore, Singapore .
authors: Janani
authors: J
authors: Manivannan
authors: Department of Singapore Institute of Neurotechnology, National University of Singapore , Singapore, Singapore .
authors: Soo Min
authors: SM
authors: Chua
authors: Department of Orthopaedic Surgery, National University of Singapore , Singapore, Singapore .|4 Department of Biomedical Engineering, Johns Hopkins School of Medicine , Baltimore, Maryland.|5 Department of Neurology, Johns Hopkins School of Medicine , Baltimore, Maryland.
authors: Angelo H
authors: AH
authors: All
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D054338:Cell Transdifferentiation; D065150:Cellular Reprogramming / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D044127:Epigenesis, Genetic; D006801:Humans; D008954:Models, Biological
keywords: comprehensive review; differentiation; induced pluripotent; transdifferentiation