Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells

Abstract

Stem cell therapy, which promotes stem cells differentiation toward specialized cell types, increases the resident population and production of extracellular matrix, and can be used to achieve intervertebral disc (IVD) repair, has drawn great attention for the development of IVD-regenerating materials. Many materials that have been reported in IVD repair have the ability to promote stem cells differentiation. However, due to the limitations of mechanical properties, immunogenicity and uncontrollable deviations in the induction of stem cells differentiation, there are few materials that can currently be translated into clinical applications. In addition to the favorable mechanical properties and biocompatibility of IVD materials, maintaining stem cells activity in the local niche and increasing the ability of stem cells to differentiate into nucleus pulposus (NP) and annulus fibrosus (AF) cells are the basis for promoting the application of IVDregenerating materials in clinical practice. The purpose of this review is to summarize IVD-regenerating materials that focus on stem cells strategies, analyze the properties of these materials that affect the differentiation of stem cells into IVD-like cells, and then present the limitations of currently used disc materials in the field of stem cell therapy and future research perspectives.

An Injectable Hyaluronan–Methylcellulose (HAMC) Hydrogel Combined with Wharton’s Jelly-Derived Mesenchymal Stromal Cells (WJ-MSCs) Promotes Degenerative Disc Repair

“…To overcome obstacles for successful disc repair, the selection of appropriate stem cells and the development of biomaterial-based cellular delivery systems that combine cells with cell-carrying matrix molecules such as fibrin and hyaluronan have become increasingly implemented [ 3 ]. Recently, various types of biomaterials have been reported to have the ability to prevent cell leakage and promote cell survival and stem cell differentiation toward the IVD cell phenotype [ 39 ]. Reports demonstrated that utilization of a carrier such as hyaluronan or annular sealant significantly prevented cell leakage, and the rate of osteophyte formation resulting from cell leakage has been reported to be less than 2.7% in rabbit IVD model [ 40 ].…”

Intervertebral disc decellularisation: progress and challenges

“…The storage modulus (G') of g-DAF-G was superior to that of DAF-G and increased with higher concentration of genipin (DAF-G: 465.51 Pa; 0.01 % genipin: 2.57 MPa; 0.02 % genipin: 3.29 MP; 0.04 %genipin: 4.34 MPa). Therefore, g-DAF-G showed improved biomechanical properties when compared to DAF-G (Peng et al, 2020).…”

“…However, other cell types and different repopulation methods have been widely investigated. As summarised in Table 3, successful recellularisation of IVD scaffolds [either injectable (Illien-Junger et al, 2016;Lin et al, 2016;Peng et al, 2020;Wachs et al, 2017;Xu et al, 2019;Yu et al, 2020;Zhou et al, 2018) or not] has already been reported with bovine and human (Illien-Junger et al, 2016;Wachs et al, 2017) NP cells as well as with rabbit (Liu et al, 2019) [either stem or not (Xu et al, 2014)] and human (Huang et al, 2016) AF cells.…”

“…Badylak's group demonstrated that a high dose of gamma-irradiation (30 kGy) prevented hydrogel formation from ECM of several tissues (porcine intestinal submucosa, liver and urinary bladder, bovine bone), when compared to the supercritical CO 2 method (White et al, 2018). Finally, Peng et al (2020) All in all, it is crucial to choose an adequate sterilisation method to maximise the properties and in vivo performance of biomaterials (Destefani et al, 2017).…”

“…Moreover, MSCs have long-term self-renewal capability, are reservoirs of growth factors and cytokines and can contribute to the restoration of the disc matrix (Wang et al, 2015;Watanabe et al, 2010;Yang et al, 2008;Zhang et al, 2005). MSCs used for IVD regeneration studies are mainly bone-marrowor adipose-tissue-derived as they can be obtained through minimally invasive procedures (Huang et al, 2016;Illien-Junger et al, 2016;Lin et al, 2016;Mercuri et al, 2011;Mercuri et al, 2013;Peng et al, 2020;Yu et al, 2020;Yuan et al, 2013;Zhou et al, 2018). However, stem cells from other sources such as amniotic fluid (Fernandez et al, 2016) or synovial tissue (Pei et al, 2012;Shoukry et al, 2013) also exhibit promising results.…”