Journal Article Review Epublish
PubMed: 40248767 DOI: 10.1016/j.reth.2025.03.007
Targeting p53-p21 signaling to enhance mesenchymal stem cell regenerative potential.
Regen Ther 29:352-363
Authors: Ahsas Goyal, Muhammad Afzal, Nawaid Hussain Khan, Kavita Goyal, Suresh Kumar Srinivasamurthy, Gaurav Gupta, K Benod Kumar, Haider Ali, Mohit Rana, Ling Shing Wong, Vinoth Kumarasamy, Vetriselvan Subramaniyan
Affiliations
- Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah 21442, Saudi Arabia.
- Faculty of Medicine, Ala-Too International University, Bishkek, Kyrgyz Republic.
- Department of Biotechnology, Graphic Era (Deemed to be University), Clement Town, Dehradun 248002, India.
- Department of Pharmacology, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical & Health Sciences University, P.O. Box 11172, Ras Al Khaimah, United Arab Emirates.
- Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India. Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates.
- Department of General Surgery, Consultant Head and Neck Surgical Oncology, Dr.D.Y.Patil Medical College, Hospital and Research Centre, Pimpri, Pune, India.
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.
- Faculty of Health and Life Sciences, INTI International University, Nilai 71800, Malaysia.
- Department of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, 56000, Kuala Lumpur, Malaysia.
- Division of Pharmacology, Faculty of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500 Selangor Darul Ehsan, Malaysia.
Abstract
Mesenchymal stem cells (MSCs) are properties of self-renewal and differentiation potentials and thus are very appealing to regenerative medicine. Nevertheless, their therapeutic potential is frequently constrained by senescence, limited proliferation, and stress-induced apoptosis. The key role of the p53-p21 biology in MSC biology resides in safeguarding genomic stability while promoting senescence and limiting regenerative capacity upon over-activation demonstrated. This pathway is a key point for improving MSC function and exploiting the inherent limitations. Recent advances indicate that senescence can be delayed by targeting the p53-p21 signaling and improved MSC proliferation and differentiation capacity. PFT-α pharmacological agents transiently inhibit p53 from increasing proliferation and lineage-specific differentiation, while antioxidants such as hydrogen-rich saline and epigallocatechin 3 gallate (EGCG) suppress oxidative stress and attenuate p53 p21 signaling. Genetic tools like CRISPR-Cas9 and RNA interference also precisely modulate TP53 and CDKN1A expression to optimize MSC functionality. The interplay of p53-p21 with pathways like Wnt/β-catenin and MAPK further highlights opportunities for combinatorial therapies to enhance MSC resilience and regenerative outcomes. This review aims to offer a holistic view of how p53-p21 targeting can further the regenerative potential of MSCs, resolving senescence, proliferation, and stress resilience towards advanced therapeutics built on MSCs.
MeSH
Cells, Microscopy, Electron, Scanning Transmission, Stress, Physiological, Stem Cells, Mesenchymal Stem Cells, Genes, P53, Therapeutics