Table 1.

Summary of therapeutic strategies discussed in the review.

Study(s)	Results and mechanism	References
TGF-β injections in degenerate mouse IVD	Results: increased cellularity and disc height Mechanism: TGF-β regulates synthesis of collagen and proteoglycans and has a role in IVD anaerobic metabolism	Walsh et al.42
Rabbit IVDs exposed to injections of BMP-7	Results: restoration of disc height and increased proteoglycan content Mechanism: bone morphogenetic protein (BMP) is a multi-functional growth factor. Increases synthesis of proteoglycans, regulates mRNA expression of type II collagen and serves as a mitotic agent.	Le Maitre et al.23 and Masuda et al.43
NP cells injected in degenerative disc disease rabbit models	Results: reduction in the decline of disc height, increased T2-weighted signal intensity, and higher glycosaminoglycan (GAG) content Mechanism: increase NP cellularity	Feng et al.44
(a) PRP delivery via gelatine-based hydrogel microspheres into the NP of degenerated rabbit discs; (b) addition of PRP in degenerated IVD of rat model; (c) PRP injections in degenerated IVD of rabbit model	Results: (a) significant suppressed progression of disease; (b) MRI findings of retained morphological features, reduced inflammatory cells and increased water content; (c) significant restoration of disc height and recruitment of chondrocyte-like cells Mechanism: activated platelets in PRP release over 70 bioactive factors	Nagae et al.30 and Obata et al.31
IVD cells transfected with adenovirus-mediated SOX9	Results: increased proliferation and synthesis of proteoglycans Mechanism: SOX9 has been found to be an important transcription factor in the process of type II collagen synthesis	Paul et al.57
In vivo implantation of AF cells seeded in atelocollagen scaffolds in rabbit model	Results: prevented progression of IVD space narrowing. AF cells had viability and proliferative activity Mechanism: atelocollagen provides a biocompatible environment that augments NP cell function	Sato et al.63, Sakai et al.64 and Sato et al.65
MSCs in collagen hydrogel were injected into the NP of damaged rabbit IVDs	Results: significant differences in disc height after 8 weeks compared to discs injected with cell-free hydrogel and untreated discs Mechanism: the use of collagen-mixed mediums in a gel-like form similar to the consistency of native NP and exposure to low levels of oxygen enhances MSC differentiation towards NP cell type	Subhan et al.4 and Kumar et al.66
(a) Biphasic scaffold was fabricated in which silk proteins were used for AF and fibrin and hyaluronic acid (HA) gels for NP. AF cells and chondrocytes were seeded onto scaffold; (b) implantation of integrated biphasic IVD comprised freeze-dried and cross-linked porcine bone matrix gelatine for the AF and porcine acellular cartilage for ECM for the NP in nude mice. AF and NP were seeded with porcine cells native to respective fractions.	Results: (a) AF and NP tissues stimulated and effective formation of total IVD in vitro; (b) IVD-like tissue was observed in this model after 6 weeks of implantation Mechanism: biphasic scaffolds recapitulate the unique structures and functions of both NP and AF	Choy and Chan75, Elsaadany et al.76, Park et al.77 and Xu et al.78
(a) Autologous bone marrow MSCs injected into the NP of 10 patients with chronic back pain; (b) two patients had autologous MSC’s implanted percutaneously in degenerated IVD	Results: (a) improvement of clinical symptoms in 1 year with no adverse events but no changes on MRI; (b) improvement of clinical symptoms at 2-year follow-up	Orozco et al.87 and Yoshikawa et al.88
Re-implantation of isolated IVD disc cells stimulated in conditioned media from damaged IVD back into the same degenerated areas in canine model	Results: at 2-year follow-up, there was disc cell viability, proliferative capacity, extracellular matrix synthetic ability, proteoglycan content, and reduction in pain scores	Meisel et al.89

TGF-β: transforming growth factor beta; IVD: intervertebral disc; NP: nucleus pulposus; PRP: platelet-rich plasma; AF: annulus fibrosus; MSC: mesenchymal stem cell.