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.
