Cell sources proposed for nucleus pulposus regeneration

Abstract

Lower back pain (LBP) occurs in 80% of adults in their lifetime; resulting in LBP being one of the biggest causes of disability worldwide. Chronic LBP has been linked to the degeneration of the intervertebral disc (IVD). The current treatments for chronic back pain only provide alleviation of symptoms through pain relief, tissue removal, or spinal fusion; none of which target regenerating the degenerate IVD. As nucleus pulposus (NP) degeneration is thought to represent a key initiation site of IVD degeneration, cell therapy that specifically targets the restoration of the NP has been reviewed here. A literature search to quantitatively assess all cell types used in NP regeneration was undertaken. With key cell sources: NP cells; annulus fibrosus cells; notochordal cells; chondrocytes; bone marrow mesenchymal stromal cells; adiposederived stromal cells; and induced pluripotent stem cells extensively analyzed for their regenerative potential of the NP. This review highlights: accessibility; expansion capability in vitro; cell survival in an IVD environment; regenerative potential; and safety for these key potential cell sources. In conclusion, while several potential cell sources have been proposed, iPSC may provide the most promising regenerative potential.

Clinical Development of Regenerative Medicine Targeted for Intervertebral Disc Disease

“…Finally, all regenerative strategies are primarily focused on restoring the NP. Cell products designed for AF or endplate restoration might provide an alternative treatment strategy or be applicable to specific patient indications [30,36,94,95]. In addition, the applicability of cell products will likely be best applied for specific patient populations and disease indications.…”

“…These cells can be sourced from multiple tissues; both are most often derived from bone marrow, adipose tissue, peripheral blood, or umbilical cords. Notably, however, the different MSC sources have been linked to differences in potency and differentiation inclinations [34][35][36]. MSC are of particular interest due to their easy accessibility and expandability [25].…”

“…For example, MSC subjected to IVD environmental factors have been shown to severely reduce proliferation and chondrogenic potency [43]. Although MSC have been shown capable of surviving and differentiating in the IVD of a range of animal models, their full NP cell phenotypical characteristics have not yet been reported [36]. Moreover, due to the unmatured nature of the MSC following transplantation and potential migration or leakage out of the IVD, they could potentially give rise to undesired differentiation and tissue formation, e.g., osteophyte as observed by Vadala et al [44].…”

“…Alternatively, other chondrogenic cells types have been suggested, specifically, chondrocytes from articular cartilage as well as hyaline cartilage tissues [43,77]. Similar to NP tissue, other articular cartilage sources are also avascular, and their cells are prone to high proteoglycan and type II collagen production and have thus been suggested and tested as an alternative cell source for IVD repair [36]. Notably, however, the rates of proteoglycan production have been shown to be much lower for articular chondrocytes compared to NP cells [78].…”

Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc

“…Cell sources for IVD repair were recently reviewed [ 33 , 34 , 35 , 36 ]. Autologous IVD cells are commonly isolated from specimens removed during surgeries, expanded, and transplanted back to augment IVD cell population.…”