A Review: Methodologies to Promote the Differentiation of Mesenchymal Stem Cells for the Regeneration of Intervertebral Disc Cells Following Intervertebral Disc Degeneration

Abstract

Intervertebral disc (IVD) degeneration (IDD), a highly prevalent pathological condition worldwide, is widely associated with back pain. Treatments available compensate for the impaired function of the degenerated IVD but typically have incomplete resolutions because of their adverse complications. Therefore, fundamental regenerative treatments need exploration. Mesenchymal stem cell (MSC) therapy has been recognized as a mainstream research objective by the World Health Organization and was consequently studied by various research groups. Implanted MSCs exert anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects and promote extracellular component production, as well as differentiation into IVD cells themselves. Hence, the ultimate goal of MSC therapy is to recover IVD cells and consequently regenerate the extracellular matrix of degenerated IVDs. Notably, in addition to MSC implantation, healthy nucleus pulposus (NP) cells (NPCs) have been implanted to regenerate NP, which is currently undergoing clinical trials. NPC-derived exosomes have been investigated for their ability to differentiate MSCs from NPC-like phenotypes. A stable and economical source of IVD cells may include allogeneic MSCs from the cell bank for differentiation into IVD cells. Therefore, multiple alternative therapeutic options should be considered if a refined protocol for the differentiation of MSCs into IVD cells is established. In this study, we comprehensively reviewed the molecules, scaffolds, and environmental factors that facilitate the differentiation of MSCs into IVD cells for regenerative therapies for IDD.

Orthobiologic Management Options for Degenerative Disc Disease

“…Alternatively, hydrogels, including those composed of hyaluronic acid, can alter the cellular environment of MSCs, prompting their differentiation into NPCs [93,94]. There are a plethora of additional pre-conditioning strategies for MSCs which are currently being examined for their effectiveness in DDD; a comprehensive review of all of these strategies has been recently published by Ohnishi et al (2023). MSCs therefore represent a diverse variety of orthobiologic treatments for DDD.…”

Glycosphingolipids in Osteoarthritis and Cartilage Regeneration Therapy: Mechanisms and Therapeutic Prospects

“…MSCs are attractive cell sources in regenerative medicine based on their abilities to self-renew and differentiate into mesenchymal tissue lineage [137]. During the last few years, the use of MSCs and their cell-free derivatives has seen an increasing number of applications in disparate medical fields, including chronic musculoskeletal conditions [138][139][140][141][142]. All of these approaches would require cell harvesting and transplantation.…”

Orthobiologic Management Options for Degenerative Disc Disease

“…Alternatively, hydrogels, including those composed of hyaluronic acid, can alter the cellular environment of MSCs, prompting their differentiation into NPCs [ 94 , 95 ]. There are a plethora of additional pre-conditioning strategies for MSCs which are currently being examined for their effectiveness in DDD; a comprehensive review of all of these strategies has been recently published by Ohnishi et al [ 96 ] MSCs therefore represent a diverse variety of orthobiologic treatments for DDD.…”