Senotherapeutics for mesenchymal stem cell senescence and rejuvenation

Pooi-Fong Wong; Murugan Dharmani; Thamil Selvee Ramasamy

doi:10.1016/j.drudis.2022.103424

Senotherapeutics for mesenchymal stem cell senescence and rejuvenation

Drug Discov Today. 2023 Jan;28(1):103424. doi: 10.1016/j.drudis.2022.103424. Epub 2022 Nov 1.

Authors

Pooi-Fong Wong¹, Murugan Dharmani¹, Thamil Selvee Ramasamy²

Affiliations

¹ Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Wilayah Persekutuan Kuala Lumpur, Malaysia.
² Stem Cell Biology Laboratory, Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, 50603 Wilayah Persekutuan Kuala Lumpur, Malaysia. Electronic address: selvee@ummc.edu.my.

PMID: 36332835
DOI: 10.1016/j.drudis.2022.103424

Abstract

Mesenchymal stem cells (MSCs) are susceptible to replicative senescence and senescence-associated functional decline, which hampers their use in regenerative medicine. Senotherapeutics are drugs that target cellular senescence through senolytic and senomorphic functions to induce apoptosis and suppress chronic inflammation caused by the senescence-associated secreted phenotype (SASP), respectively. Therefore, senotherapeutics could delay aging-associated degeneration. They could also be used to eliminate senescent MSCs during in vitro expansion or bioprocessing for transplantation. In this review, we discuss the role of senotherapeutics in MSC senescence, rejuvenation, and transplantation, with examples of some tested compounds in vitro. The prospects, challenges, and the way forward in clinical applications of senotherapeutics in cell-based therapeutics are also discussed.

Keywords: cellular senescence; rejuvenation; senolytics; senomorphics; stem cell therapy.

Publication types

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

MeSH terms

Cellular Senescence / genetics
Mesenchymal Stem Cells*
Rejuvenation
Senotherapeutics*

Substances

Senotherapeutics