Cell based therapy for IVD nucleus repair mainly aims for NP like cells injections, addressing the imbalance of biochemical environment (proteoglycan synthesis and water content). Stimulation of the residing cells is insufficient to achieve tissue repair; hence, diseased phenotype properties of the native NP cells certainly limit their use. Thus, injecting functional cells aimed to overcome this problem by compensating cell death and disc shrinkage 
. Concomitantly, Abbott et al. proposed NP cells do possess regeneration potential even in severe status of degeneration 
. Several cell-based strategies have been investigated to retard NP degeneration, using different IVD model system 
, with NP and/or AF cells, articular chondrocytes, or mesenchymal stem/stromal cells (MSCs). Feng et al. summarized GDF-5 a suitable growth factor for inducing NP-like cells based on its positive effect on the differentiation of MSCs towards an NP-like phenotype 
. The effect of growth factors such as TGF-β, IGF-1, FGF-2, PDGF and GDF-5 on the differentiation of MSCs into NP-like cells have been investigated 
. Fundamentally, the transplanted MSCs are expected to differentiate, maintain and enhance the function of existing NP cells to reverse the IDD. Thus, preclinical studies will be required to confirm the functional potency of the MSC-based therapy for IDD. Good accessibility and the ability of MSCs (bone marrow, adipose and synovial tissue derived) to differentiate into different cell types including chondrocyte like cells, promoted MSCs as prime source for cell therapies for several diseases and in IVD regenerative treatment 
. Intradiscal delivery of bone marrow and adipose derived MSCs has demonstrated to promote regeneration by maintaining cell viability and proliferation, obtaining IVD-like phenotypes, and providing expression of typical chondrocyte markers, in several studies using rabbit, rat, dog, and goat models 
. Nevertheless, one common problem affecting the healing satisfaction is the tendency of hypertrophic differentiation of MSCs 
. How to achieve an ideal IVD repair mainly relies on manipulation of hypertrophic chondrogenesis of the injected and/or implanted MSCs.
In parallel, the use of notochordal cells is also being considered, no matter from allogenic, autologous or xenogenic origin 
. Risbud et al. has previously proposed that morphology and size variation correlates to different stages of maturation and/or function of NP cells derived from notochordal precursors 
. Moreover, it has been speculated that degeneration is due to the selective loss of the notochordal cells fraction while considering overall reduction in the structural and functional activity of IVD cells. While there is considerable agreement, Bach et al. demonstrated the species (human, canine and porcine) specific regenerative effects of notochordal cell conditioned medium on human NP cells. It further confirmed the canine and porcine secreted factors exerted regenerative effect on human NP cells 
. The fact that NP cells with diseased phenotype possess regeneration potential, allows autologous NP cells to be expanded using conditioned medium that these cells can be used as a source for cell therapy during nucleus repair. Likewise, stem cells can be differentiated towards NP like cell type. van Uden et al. has already addressed 
the importance of hypoxia during NP repair. This key factor may restrict the success of the stem cell based therapy, as stem cells tend to die due to lack of oxygen. Serigano et al. demonstrated the effect of cell number on mesenchymal stem cell transplantation in canine disc degeneration model, where they showed high possibility of apoptosis, low cell viability, while maintaining microenvironment during stem cell transplantation 
. Altogether, it affected the regeneration capability. However, in order to advance clinical translation of cell therapy, assessment of in vivo integration (in terms of functional and mechanical repair) in large animals is necessary. Therefore, a comparative analysis of cell types and sources of cells using large animal models is essential to enlighten the suitable strategy.