The nucleus pulposus microenvironment in the intervertebral disc: the fountain of youth?

J , Guerrero,As Croft,B Gantenbein,Ce Albers,S Hoppe,S Häckel

doi:10.22203/ecm.v041a46

Abstract

The intervertebral disc (IVD) is a complex tissue, and its degeneration remains a problem for patients, without significant improvement in treatment strategies. This mostly age-related disease predominantly affects the nucleus pulposus (NP), the central region of the IVD. The NP tissue, and especially its microenvironment, exhibit changes that may be involved at the outset or affect the progression of IVD pathology. The NP tissue microenvironment is unique and can be defined by a variety of specific factors and components characteristic of its physiology and function. NP progenitor cell interactions with their surrounding microenvironment may be a key factor for the regulation of cellular metabolism, phenotype, and stemness. Recently, celltransplantation approaches have been investigated for the treatment of degenerative disc disease, highlighting the need to better understand if and how transplanted cells can give rise to healthy NP tissue. Hence, understanding all the components of the NP microenvironment seems to be critical to better gauge the success and outcomes of approaches for tissue engineering and future clinical applications. Knowledge about the components of the NP microenvironment, how NP progenitor cells interact with them, and how changes in their surroundings can alter their function is summarised. Recent discoveries in NP tissue engineering linked to the microenvironment are also reviewed, meaning how crosstalk within the microenvironment can be adjusted to promote NP regeneration. Associated clinical problems are also considered, connecting bench-to-bedside in the context of IVD degeneration.

Highlights

The intervertebral disc (IVD) can be defined as a joint between adjacent vertebral bodies
Even nucleus pulposus (NP) progenitor cells derived from degenerated IVDs still retain their regeneration ability. They may be a promising cell candidate for cell-based regenerative medicine and tissue engineering for IVD degeneration. These results suggest that Tie2+ NPCs could play a crucial role in IVD regeneration, knowing that – even if their microenvironment is disrupted – they do not seem to be affected (Sakai et al, 2012)
Feng et al (2014), cultured NP bovine cells for 3 weeks in a 3D environment with different oxygen tension levels (2 % to 20 %). They demonstrated that, even after 8 weeks of in vivo implantation, the hypoxic priming of NP cells resulted in the maintenance of GAG, collagen type II, aggrecan, and SOX-9 expression compared to normoxic priming

Summary

Introduction

The IVD can be defined as a joint between adjacent vertebral bodies. It is composed of three primary tissues, the NP, the AF, and the CEP (Urban and Roberts, 2003). It is well documented that disc degeneration first occurs in the NP region of the IVD (Wang et al, 2014; Zhao et al, 2007). In this context, this full microenvironment (i.e. ECM and non-ECM related factors) of the IVD, and especially the NP microenvironment is believed to play a critical role in the regulation and maintenance of this tissue. This full microenvironment (i.e. ECM and non-ECM related factors) of the IVD, and especially the NP microenvironment is believed to play a critical role in the regulation and maintenance of this tissue It can potentially improve the repair and regeneration of the vertebral column joint (Fig. 1). The understanding of the NP microenvironment of the IVD is still incomplete

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