Stem Cell Approaches to Intervertebral Disc Regeneration: Obstacles from the Disc Microenvironment

Abstract

Intervertebral disc (IVD) degeneration results in segmental instability and irritates neural compressive symptoms, such as low back pain and motor deficiency. The transplanting of stem cell into degenerative discs has attracted increasing clinical attention, as a new and proven approach to alleviating disc degeneration and to relieving discogenic pains. Aside from supplementation with stem cells, the IVD itself already contains a pool of stem and progenitor cells. Since the resident disc stem cells are incapable of reversing the pathologic changes that occur during aging and disc degeneration, it has been debated as to whether transplanted stem cells are capable of providing an efficient and durable therapeutic effect, even though there have been positive outcomes in both animal models and in clinical trials. This review aims to decipher the interactions between the stem cell and the disc microenvironment. Within their new niches in the IVD, the exogenous stem cell shows metabolic adaptation to the low-glucose supply, hypoxia, and compressive loadings, but demonstrates little tolerance to the disc-like acidity and hypertonicity. Similarly, the survival of endogenous stem cells is threatened as well by the harsh disc microenvironment, which may exhaust the stem cell resources and restrict the self-repair capacity of a degenerating IVD. To eliminate the intrinsic obstacles within the stressful disc niches, stem cells should be delivered with an injectable scaffold that provides both survival and mechanical support. Quick healing or concretion of the injection injuries, which minimizes stem cell leakage and disturbance to disc homeostasis, is of equal importance toward achieving efficient stem cell-based disc regeneration.

Mechanisms of endogenous repair failure during intervertebral disc degeneration

“…Because of the poor self-repair ability of NP, it is difficult to reverse the IVD degeneration 5 . At present, it is a challenge to repair or regenerate the structure and functions of IVD via conservative or surgical treatments, as there are still many complications and problems in terms of long-term curative effects 14,15 .…”

“…The theory of the stem cell based biological treatment is to recruit endogenous IVD stem/progenitor cells and/or supplement exogenous mesenchymal stem cells (MSCs) to the IVD tissues, and then induce the differentiation of stem cells into IVD cells and/or protect the IVD cells, so as to increase the quantity and quality of IVD cells for the repair and regeneration of the degenerative IVD 17 . However, endogenous IVD stem/progenitor cell based endogenous repair processes fail to prevent IVD degeneration, which has been indicated as a major cause of IVD degeneration 5,14,18 . The latest research suggests that IVD stem/progenitor cells play a crucial role in endogenous IVD repair, and how to maintain a sufficient number of stem cells with vitality under adverse microenvironments in the IVD, such as compression and hypoxia, is an important issue needing to solve 19,20 .…”

The effect of high glucose on the biological characteristics of nucleus pulposus‐derived mesenchymal stem cells

“…However, MSC transplantation still remains several difficulties and challenging. The viability, proliferation and matrix synthesis of the transplanted MSC in the acidic condition, hypoxia, hyperosmolarity and poor nutrients microenvironment are significantly suppressed . Risbud et al firstly provided evidence for the existence of endogenous MSC‐like progenitor cells in human nucleus pulposus (NP) in 2007 .…”

Cell properties of nucleus pulposus progenitor cells declines with intervertebral disc degeneration

“…The tissue microenvironment is still thought to play an important role in maintaining SC proliferation and differentiation [29,30]. In addition, cell properties decrease with age and degeneration during IDD progression [31].…”