# Advances in Tissue Engineering for Disc Repair
## 3 Tissue Engineering for IVD Regeneration  
Although many studies have reported alternative biological treatments for IVDD, these approaches have certain limitations. Direct administration of growth factors is associated with the short half-life of growth factors and potential lack of IVD cells as therapeutic targets in severe disc degeneration [29]. Gene therapy has several disadvantages, including inefficient gene delivery, unstable long-term expression, and lack of safety. While cell-based therapies have shown more promising therapeutic potential, the best strategies for effectiveness and safety have yet to be addressed [29]. In a clinical setting, stem cells are implanted in a harsh environment consisting of low cellularity, low glucose, low oxygen, low PH due to high lactic acid accumulation, low nutrients, and an inflammatory milieu [6; 51; 52; 53]. Inflammatory mediators are a key component of progressive IVDD. All these factors can affect the differentiation potential, viability, and metabolism of the implanted stem cells [52]. MSCs can function optimally in inflammatory, hypoxic, acidic, and malnourished environments of the degenerated disc and have an immunomodulatory paracrine effect [52; 54; 55]. Hypoxia-exposed human MSCs (hMSCs) have been reported to improve tissue protection, but exposure of MSCs to inflammatory factors or hypoxic environment may adversely affect MSC differentiation. Therefore, it is important and necessary to design scaffolds \begin{table}
\begin{tabular}{c c c} \hline
**Author** & **Cell Line** & **Effect** \\ \hline
2019, [PERSON] et al. [40] & Neonatal human dermal fibroblasts & Increased regeneration markers \\
2019, [PERSON] et al. [33] & Rabbit, in vivo & Reduction of disc degeneration in a porcine model \\  & Notochordal cells from human iPSCs & \\ \hline
2018, [PERSON] et al. [41] & Human BM-MSC & Promoted cell migration and increased inflammatory \\  & Bovine, ex-vivo & cytokine expression \\ \hline  & & Hypoxic pre-treatment of BM-MSC with CoCl\({}_{2}\) \\
2018, [PERSON] et al. [42] & Rat BM-MSC & enhanced migration, decreased apoptosis, increased \\  & Rat, in vivo & disc height, MSC numbers in the NP and AF, and \\  & & extracellular matrix production \\ \hline
2017, [PERSON] et al. [43] & Allogeneic rat BM-MSC & Cell therapies administered at an early stage of \\  & Rat, in vivo & injury or disease progression may have greater \\  & & chances of mitigating matrix loss \\ \hline
2017, [PERSON] et al. [44] & Autologous canine BM-MSC & PET was more reliable than MRI for quantifying \\  & Canine, in vivo & implanted BM-MSC survival \\ \hline
2017, [PERSON] et al. [45] & Autologous canine BM-MSC & Successful injection of BM-MSC into lumbosacral \\  & Canine, in vivo & discs of naturally IVD-degenerative canines \\ \hline
2017, [PERSON] et al. [46] & Allogeneic EM-MSC & Significant VAS and ODI reductions, improvement \\  & Clinical trial (N = 24, follow-up: 12 months) & on MRI \\ \hline
2017, [PERSON] et al. [47] & Autologous BM-MSC & Disc bulging reduction on MRI, pain and function \\  & Clinical trial (N = 33, follow-up: 72 months) & improvement \\ \hline
2017, [PERSON] et al. [48] & Autologous AD-MSC & Combined implantation of AD-MSC and hyaluronic \\  & Clinical trial (N = 10, follow-up: 12 months) & acid in disogenic back pain is safe and tolerable \\ \hline
2017, [PERSON] et al. [49] & Autologous BM-MSC & Evidence for the safety and feasibility of intradiscal \\  & Clinical trial (N = 26, follow-up: 36 months) & BM concentrate therapy \\ \hline
2016, [PERSON] et al. [50] & Autologous disc chondrocyte & Ongoing study \\  & Clinical trial (N = 120, follow-up: 48 months) & Ongoing study \\ \hline \end{tabular} BM-MSC, bone marrow-derived mesenchymal stem cell; AD-MSC, adipose tissue-derived mesenchymal stem cell; NP, nucleus pulposus; AF, annulus fibrous; VAS, visual analogue scale; ODI, Oswestry disability index; iPSC, induced pluripotent stem cell; IVD, intervertebral disc.  
\end{table} 
Table 1: Cell-based therapies for IVD regeneration.