Mesenchymal stem cells: potential application in intervertebral disc regeneration

Abstract

Chronic low back pain is one of the leading public health problems in developed countries. Degeneration of the intervertebral disc (IVD) is a major pathological process implicated in low back pain, which is characterized by cellular apoptosis and senescence with reduced synthesis of extracellular matrix (ECM). Currently, there is no clinical therapy targeting the reversal of disc degeneration. Recent advances in cellular and molecular biology have provided an exciting approach to disc regeneration that focuses on the delivery of viable cells to the degenerative disc. Adult mesenchymal stem cells (MSCs) are multipotent stem cells with self-renewal capacities and are able to differentiate into diverse specialized cell types, including chondrocyte lineages. The potential of stem cell therapy in disc degeneration is to repopulate the disc with viable cells capable of producing the ECM and restoring damaged tissue. The present literature review summarizes recent advances in basic research and clinical trials of MSCs to provide an outline of the key roles of MSCs therapies in disc repair. The review also discusses the controversies, challenges and therapeutic concepts for the future.

Keywords: Mesenchymal stem cell (MSC); back pain; degeneration; intervertebral disc (IVD); regeneration.

Figure 1

Diagram of the human intervertebral disc.

Figure 2

Histological characteristics of healthy human nucleus pulposus. (Left panels) A tissue sample of a healthy human disc from a 16-year-old individual shows sparse chondrocyte-like cells within the nucleus pulposus producing abundant collagen and proteoglycan. Staining with H&E shows morphology (top), Alcian blue (blue staining) identifies proteoglycan (middle) and safranin-O identifies collagen (orange staining, bottom), (magnification 40×). (Right panels) A sample of 14-week-old fetal spine tissue illustrates the NP as highly cellular, containing large vacuolated NC which produce a matrix rich in proteoglycan (magnification 10×, top and middle; 40×, bottom). H&E, haematoxylin & eosin; NC, notochordal cells.

Figure 3

Histological characteristics of healthy human annulus fibrosus. (Left panels) A sample of a healthy human disc from a 16-year-old individual illustrates the cells in the AF embedded in collagen fibres. Morphology and proteoglycan are visible, (Magnification 40×). (Right panels) A sample of 14-week-old fetal spine tissue showing that the AF has already become well organized into a lamellar pattern (40×, top). Lamellar striations are visible at both low (10×, middle) and high (40×, bottom) magnification when stained with Alcian blue.

Figure 4

Coculture system and ultrastructural appearance of MSCs following coculture with disc tissue. (A) Schematic diagram of the experimental co-culture process; (B) Ultrastructural appearance of MSCs in co-culture with intact disc tissue, day 14 visualised by scanning electron microscopy. Representative SEM images revealed that most of the co-cultured rMSCs appeared to be spherical or irregular in shape. Some cells have long membrane processes extending from the co-cultured rMSCs through the pores of the transwell-membrane toward the neighbouring disc cells on the underside.