# Advances in Tissue Engineering for Disc Repair
## 2 Biological Approaches
### Cell-Based Therapies  
In the intermediate stages of IVDD, cell transplantation can be used to repopulate the disc. Although the NP cell phenotype has not been well defined, the adult NP contains cells similar to chondrocyte [31]. Cell transplantation to a moderately degenerated disc is a possible treatment that promotes disc regeneration by reproliferating cells that can restore the structural and functional properties of the degenerated disc or delay degeneration [27].  
An optimal source of cells suitable for cell transplantation in the degenerative disc remains elusive. Several studies have demonstrated that implantation of IVD-derived cells delays the process of progressive degeneration and, in some cases, promotes disc regeneration in an animal model of IVDD [32; 33]. However, since these cells are derived from normal NP tissue, they cannot be obtained without damaging the IVD [25].  
Stem cells are a promising candidate cell source for use in cell-based therapies for IVD repair. Most of the stem cells used in disc regeneration experiments are derived from the bone marrow, adipose tissue, umbilical cord blood, umbilical cord Wharton's jelly, and synovium, because these cells are relatively easy to obtain and can differentiate into chondrogenic and IVD-cell lineages [34; 35]. Implantation of MSCs into degenerated discs can prevent cellular apoptosis and inflammation (paracrine effect) or differentiate MSCs into NP cells to restore normal homeostasis and prevent or reverse further degeneration [13]. Injecting stem cells into the degenerated disc has been reported to increase the proteoglycan and water contents of the disc ECM (Table 1) [29].  
Notochondral cells have been suggested to cause disc degeneration because their loss is associated with the onset of IVDD [33]. [PERSON] et al. demonstrated that notochordal-like cells from human induced pluripotent stem cells (iPSCs) reduce IVDD in an injury-induced porcine model [33]. Therefore, the application of iPSCs is a hot topic in the field of IVD regeneration and has several advantages over embryonic stem cells (ESCs), such as fewer ethics and immune rejection issues [33]. However, iPSCs also have drawbacks in clinical applications, such as tumor formation by genomic integration of reprogramming factors [36].  
For the clinical application of stem cells for IVD regeneration, MSCs treatment strategies, cell doses, and efficacy are being investigated in various experimental settings of IVDD and clinical trials [37]. The use of MSCs is generally considered safe and effective in preventing IVDD, but the rate of osteophyte formation has been reported to be around 2.7% [37; 38]. Osteophyte formation is believed to be the result of implanted MSC leakage. Therefore, the application of scaffolding materials, such as fibrin, hyaluron, or atelo-collagen, is strongly recommended to prevent cell leakage and reduce the risk of ectopic osteoblast differentiation of MSCs [39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49; 50].  
To summarize, stem cell therapy can be used to induce IVD repair by preventing cellular apoptosis and inflammation, and by increasing the resident population and ECM production, and there is great interest in developing biomaterials for effective cell delivery, increasing cell viability, and inducing differentiation of stem cells into IVD-like cells.