Mechanisms of endogenous repair failure during intervertebral disc degeneration

Abstract

Intervertebral disc (IVD) degeneration is frequently associated with Low back pain (LBP), which can severely reduce the quality of human life and cause enormous economic loss. However, there is a lack of long-lasting and effective therapies for IVD degeneration at present. Recently, stem cell based tissue engineering techniques have provided novel and promising treatment for the repair of degenerative IVDs. Numerous studies showed that stem/progenitor cells exist naturally in IVDs and could migrate from their niche to the IVD to maintain the quantity of nucleus pulposus (NP) cells. Unfortunately, these endogenous repair processes cannot prevent IVD degeneration as effectively as expected. Therefore, theoretical basis for regeneration of the NP in situ can be obtained from studying the mechanisms of endogenous repair failure during IVD degeneration. Although there have been few researches to study the mechanism of cell death and migration of stem/progenitor cells in IVD so far, studies demonstrated that the major inducing factors (compression and hypoxia) of IVD degeneration could decrease the number of NP cells by regulating apoptosis, autophagy, and necroptosis, and the particular chemokines and their receptors played a vital role in the migration of mesenchymal stem cells (MSCs). These studies provide a clue for revealing the mechanisms of endogenous repair failure during IVD degeneration. This article reviewed the current research situation and progress of the mechanisms through which IVD stem/progenitor cells failed to repair IVD tissues during IVD degeneration. Such studies provide an innovative research direction for endogenous repair and a new potential treatment strategy for IVD degeneration.

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

“…However, with prolonged loading, NPCy irreversibly undergo apoptosis through caspase-dependent mitochondrial pathways. In addition, a specific form of programmed cell death with necrosis-like features, namely, necroptosis, seems to be involved in the compression-induced death of NPCy [106].…”

The protective effects of PI3K/Akt pathway on human nucleus pulposus mesenchymal stem cells against hypoxia and nutrition deficiency

“…The aim of endogenous hNP-MSCs therapy is to make hNP-MSCs differentiate into NP-like cells and promote disc cells maintaining metabolic balance and biomechanical functions of IVD. However, it is hard to maintain the number of the active hNP-MSCs under the adverse microenvironment in the degenerated IVD and leads to repair failure of endogenous hNP-MSCs [11].…”

Moderate Fluid Shear Stress Regulates Heme Oxygenase-1 Expression to Promote Autophagy and ECM Homeostasis in the Nucleus Pulposus Cells

“…Low back pain is a common and frequently recurring musculoskeletal disorder, which causes heavy financial burden worldwide (Chen et al, 2017;Clouet et al, 2018;Ma et al, 2019). Epidemiological investigations show that over 80% of the world population will experience LBP at some point in their life, and LBP has become the leading cause of years lived with disability and the second most common reason for hospital visits (Maher et al, 2017;Henry et al, 2018;Chen et al, 2019).…”