Targeting cell plasticity for regeneration: From in vitro to in vivo reprogramming

Sara Romanazzo; Kang Lin; Pallavi Srivastava; Kristopher A Kilian

doi:10.1016/j.addr.2020.08.007

Targeting cell plasticity for regeneration: From in vitro to in vivo reprogramming

Adv Drug Deliv Rev. 2020:161-162:124-144. doi: 10.1016/j.addr.2020.08.007. Epub 2020 Aug 19.

Authors

Sara Romanazzo¹, Kang Lin², Pallavi Srivastava³, Kristopher A Kilian⁴

Affiliations

¹ School of Chemistry, Australian Centre for Nanomedicine, University of New South Wales, Sydney, NSW, Australia.
² School of Materials Science and Engineering, University of New South Wales, Sydney, NSW, Australia.
³ School of Chemistry, Australian Centre for Nanomedicine, University of New South Wales, Sydney, NSW, Australia; School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
⁴ School of Chemistry, Australian Centre for Nanomedicine, University of New South Wales, Sydney, NSW, Australia; School of Materials Science and Engineering, University of New South Wales, Sydney, NSW, Australia. Electronic address: k.kilian@unsw.edu.au.

PMID: 32822682
DOI: 10.1016/j.addr.2020.08.007

Abstract

The discovery of induced pluripotent stem cells (iPSCs), reprogrammed to pluripotency from somatic cells, has transformed the landscape of regenerative medicine, disease modelling and drug discovery pipelines. Since the first generation of iPSCs in 2006, there has been enormous effort to develop new methods that increase reprogramming efficiency, and obviate the need for viral vectors. In parallel to this, the promise of in vivo reprogramming to convert cells into a desired cell type to repair damage in the body, constitutes a new paradigm in approaches for tissue regeneration. This review article explores the current state of reprogramming techniques for iPSC generation with a specific focus on alternative methods that use biophysical and biochemical stimuli to reduce or eliminate exogenous factors, thereby overcoming the epigenetic barrier towards vector-free approaches with improved clinical viability. We then focus on application of iPSC for therapeutic approaches, by giving an overview of ongoing clinical trials using iPSCs for a variety of health conditions and discuss future scope for using materials and reagents to reprogram cells in the body.

Keywords: Biophysical factors; Cell reprogramming; Cell therapy; Direct reprogramming; Small molecules; iPSC.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Biological Specimen Banks
Cardiovascular Diseases / physiopathology
Cell Plasticity / physiology*
Cellular Reprogramming Techniques / methods
Drug Discovery / methods
Humans
Induced Pluripotent Stem Cells / metabolism*
Liver Diseases / physiopathology
Neoplasms / physiopathology
Nervous System Diseases / physiopathology
Regeneration / physiology*
Regenerative Medicine / methods
Signal Transduction / physiology
Transcription Factors / metabolism

Substances

Transcription Factors