Mesenchymal stem cells for cartilage regeneration: Insights into molecular mechanism and therapeutic strategies

Merlin Mamachan; Khan Sharun; S Amitha Banu; Sathish Muthu; Abhijit M Pawde; Laith Abualigah; Swapan Kumar Maiti

doi:10.1016/j.tice.2024.102380

Mesenchymal stem cells for cartilage regeneration: Insights into molecular mechanism and therapeutic strategies

Tissue Cell. 2024 Apr 10:88:102380. doi: 10.1016/j.tice.2024.102380. Online ahead of print.

Authors

Merlin Mamachan¹, Khan Sharun², S Amitha Banu¹, Sathish Muthu³, Abhijit M Pawde¹, Laith Abualigah⁴, Swapan Kumar Maiti¹

Affiliations

¹ Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
² Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India; Graduate Institute of Medicine, Yuan Ze University, Taoyuan, Taiwan. Electronic address: sharunk@saturn.yzu.edu.tw.
³ Department of Biotechnology, Faculty of Engineering, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; Orthopaedic Research Group, Coimbatore, Tamil Nadu, India; Department of Orthopaedics, Government Medical College, Kaur, Tamil Nadu, India.
⁴ Artificial Intelligence and Sensing Technologies (AIST) Research Center, University of Tabuk, Tabuk 71491, Saudi Arabia; Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman 19328, Jordan; Computer Science Department, Al al-Bayt University, Mafraq 25113, Jordan; MEU Research Unit, Middle East University, Amman 11831, Jordan; Department of Electrical and Computer Engineering, Lebanese American University, Byblos 13-5053, Lebanon; Applied Science Research Center, Applied Science Private University, Amman 11931, Jordan; School of Engineering and Technology, Sunway University Malaysia, Petaling Jaya 27500, Malaysia.

PMID: 38615643
DOI: 10.1016/j.tice.2024.102380

Abstract

The use of mesenchymal stem cells (MSCs) in cartilage regeneration has gained significant attention in regenerative medicine. This paper reviews the molecular mechanisms underlying MSC-based cartilage regeneration and explores various therapeutic strategies to enhance the efficacy of MSCs in this context. MSCs exhibit multipotent capabilities and can differentiate into various cell lineages under specific microenvironmental cues. Chondrogenic differentiation, a complex process involving signaling pathways, transcription factors, and growth factors, plays a pivotal role in the successful regeneration of cartilage tissue. The chondrogenic differentiation of MSCs is tightly regulated by growth factors and signaling pathways such as TGF-β, BMP, Wnt/β-catenin, RhoA/ROCK, NOTCH, and IHH (Indian hedgehog). Understanding the intricate balance between these pathways is crucial for directing lineage-specific differentiation and preventing undesirable chondrocyte hypertrophy. Additionally, paracrine effects of MSCs, mediated by the secretion of bioactive factors, contribute significantly to immunomodulation, recruitment of endogenous stem cells, and maintenance of chondrocyte phenotype. Pre-treatment strategies utilized to potentiate MSCs, such as hypoxic conditions, low-intensity ultrasound, kartogenin treatment, and gene editing, are also discussed for their potential to enhance MSC survival, differentiation, and paracrine effects. In conclusion, this paper provides a comprehensive overview of the molecular mechanisms involved in MSC-based cartilage regeneration and outlines promising therapeutic strategies. The insights presented contribute to the ongoing efforts in optimizing MSC-based therapies for effective cartilage repair.

Keywords: Cartilage repair; Chondrogenesis; Chondrogenic differentiation; Regenerative medicine; Tissue engineering.

Publication types

Review