Intervertebral disc regeneration: From cell therapy to the development of novel bioinspired endogenous repair strategies

Abstract

Low back pain (LBP), frequently associated with intervertebral disc (IVD) degeneration, is a major public health concern. LBP is currently managed by pharmacological treatments and, if unsuccessful, by invasive surgical procedures, which do not counteract the degenerative process. Considering that IVD cell depletion is critical in the degenerative process, the supplementation of IVD with reparative cells, associated or not with biomaterials, has been contemplated. Recently, the discovery of reparative stem/progenitor cells in the IVD has led to increased interest in the potential of endogenous repair strategies. Recruitment of these cells by specific signals might constitute an alternative strategy to cell transplantation. Here, we review the status of cell-based therapies for treating IVD degeneration and emphasize the current concept of endogenous repair as well as future perspectives. This review also highlights the challenges of the mobilization/differentiation of reparative progenitor cells through the delivery of biologics factors to stimulate IVD regeneration.

Mechanisms of endogenous repair failure during intervertebral disc degeneration

“…As one of the core elements of biological treatments, stem cells play a significant role in the repair of IVD degeneration 5,16 . 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 .…”

Bandscheibenregeneration – Konzepte und Ergebnisse

“…Auch die Applikation antiinflammatorisch [28 -30] oder analgetisch [31] wirkender Moleküle wird getestet. Ein weiterer interessanter Ansatz ist Chemotaxis: So sind in und um die Bandscheibe Nischen mit verschiedenen Stamm-und Vorläuferzellen identifiziert worden, welche mit Chemokinen und anderen bioaktiven Faktoren rekrutiert und differenziert werden können [32].…”

Biomaterials for intervertebral disc regeneration: Current status and looming challenges

“…An increased rate of cell apoptosis or necrosis, altered homeostasis of extracellular matrix (ECM), and elevated levels of inflammation are the major inducers for NP degeneration. Although the NP has been regarded as a source of stem cells/progenitors (Harris & Vangsness, , Sakai, Nakamura, Nakai, et al, ), its capacity of endogenous regeneration is very limited because of the low cell density, the diminished cellular viability and activity, and the nutrient insufficiency (Clouet, Fusellier, Camus, et al, ; Huang et al, ; Liebscher, Haefeli, Wuertz, et al, ).…”