Download Tissue engineering of intervertebral disc (Prof. Sarit Sivan and Dr

Tissue engineering of intervertebral disc (Prof. Sarit Sivan and Dr. Michal Amit)
Disc degeneration and accompanying back pain (LBP) impose a major medical and societal challenge. The
normal functioning of IVD is governed by its major macromolecular constituents, collagen and the large
aggregating proteoglycan (PG), aggrecan, distributed across the central gelatinous nucleus pulposus (NP)
and the outer annulus fibrosus. Aggrecan, apart from its role in imbibing water and distributing loads, also
inhibits ingrowth of both nerve and endothelial cells. With the onset of disc degeneration, PG is lost from the
disc’s inner regions, resulting in water loss and concomitant loss of disc height. Increased innervation and
vascularization, which are related to the development of 'discogenic' LBP have also been reported. However,
IVD has the potential for self-healing due to the presence of progenitor cells, specifically notochordal cells,
which participate in disc development. With the onset of disc degeneration, NP cells produce less
extracellular matrix (ECM), which limits disc regeneration potential. Nevertheless, the activity of NP cells can
be regained by co-culturing them with mesenchymal stem cells (MSCs).Unfortunately, the retention and
viability of injected MSCs are poor due to a lack of anchorage; the use of biomaterials, such as alginate,
collagen, chitosan and hyaluronan, as delivery vehicles, can provide protection from the hostile environment
in the degenerated disc and promote their retention in the injection site. However, while able to maintain cell
phenotype and encourage ECM production, none of these materials possess the mechanical characteristics of
the native disc tissue.
The main goals of our study is to test the capability of a novel series of biomimetic GAG analogues,
developed by Sivan et al., to function as BM-MSC carriers and to promote the production of NP-like ECM via
cues delivered to the cells by their unique structural characteristics. To this aim, BM-MSCs will be cultured in
GAG analogue hydrogels of different stiffness; constructs will be incubated under IVD-like conditions of
osmolarity in the presence and absence of differentiation factors. Constructs will be tested for tissue
organization and assessed for cell viability, biochemical composition and for the presence of NP-phenotype
markers using gene expression. The ability of GAG analogues to delay nerve growth will also be assessed.