Notochordal Cell Produce and Assemble Extracellular Matrix in a Distinct Manner, Which May Be Responsible for the Maintenance of Healthy Nucleus Pulposus

Abstract

Our model shows that a change in intervertebral disc cell phenotype correlates with the grade of disc degeneration and that the notochordal cells synthesize proteoglycans, which exhibit delayed aggregation than those synthesized by the small nucleus pulposus cells. This implies that the cell type composition of the nucleus pulposus of the chondrodystrophoid and nonchondrodystrophoid dogs produces an extracellular matrix that is assembled in a distinct manner, which may affect tissue integrity.

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

“…Notochordal cells have been shown to produce more proteoglycans than smaller NP cells [69] and, when in coculture, notochordal cells interact with small NP cells stimulating them to produce a healthier extracellular matrix [70,71]. Recent findings also show that notochordal cells can prevent Il-1-induced cell death in small NP cells [72].…”

The enigma that is the nucleus pulposus cell: the search goes on

“…[5]. Is it a dose-response issue whereby the discs that are relatively deficient in notochordal cells are therefore lacking in the necessary and sufficient molecules synthesized by these cells that may act upon the NP cell [6,7]?…”

“…Is it a dose-response issue whereby the discs that are relatively deficient in notochordal cells are therefore lacking in the necessary and sufficient molecules synthesized by these cells that may act upon the NP cell [6,7]? It is thought that the notochordal cell-rich disc NP phenotype confers superior biomechanical properties [5,8]. Do notochordal cell-deficient discs therefore fail to resist the loads imposed by daily life over time due to biomechanical or biochemical reasons - or both?…”

Physical Limitations to Tissue Engineering of Intervertabral Disc Cells

“…Aguiar et al have suggested that the notochordal cells found in the human nucleus pulposus up to approximately 10 years of age play an active role in nucleus pulposus development and in the maintenance of disc integrity through the production of soluble factors that induce nucleus pulposus cells to increase proteoglycan synthesis (Aguiar et al, 1999). Interestingly, it has been found that co-culture of immature cells such as mesenchymal stem cells with notochordal cells and adult nucleus pulposus cells (chondrocyte-like cells) stimulates proteoglycan synthesis more rapidly, and this method has been extensively used in studies on disc regeneration , Cappello et al, 2006, Erwin & Inman, 2006. However, previous studies on proteoglycan production by notochordal cells and chondrocyte-like nucleus pulposus cells have only compared proteoglycan synthesis on the basis of sulphate synthesis, and no studies have compared glycosaminoglycan accumulated by these cells.…”

“…In fact, transformation of the matrix by cells in human discs is very slow, and studies have shown that proteoglycan turnover takes about 20 years (Roughley, 2004) and collagen turnover takes more than 100 years (Verzijl et al, 2000). However, autologous transplantation of cells with a high proteoglycan production capacity such as notochordal cells and mesenchymal stem cells may lead to successful repair of degenerated discs , Aguiar et al,1999, Cappello et al, 2006, Erwin & Inman, 2006. Even if the transplantation of cells with a high proteoglycan production capacity into the nucleus pulposus is feasible, it is also essential for preventing the progression of disc degeneration that the transplanted cells survive in the degenerated disc and continue to produce appropriate macromolecules for maintenance of disc mechanical strength throughout life.…”