Understanding nucleus pulposus cell phenotype: a prerequisite for stem cell based therapies to treat intervertebral disc degeneration

Abstract

Intervertebral disc (IVD) degeneration and associated low back pain (LBP) remains a major burden to our society without significant improvements in treatment strategies or patient's quality of life. While the recent cell-transplantation studies for treatment of degenerative disc disease have shown promising results, to better gauge the success and functional outcomes of these therapies, it is crucial to understand if transplanted cells give rise to healthy nucleus pulposus (NP) tissue. NP cell phenotype is unique and is defined by expression of a characteristic set of markers that reflect specialized physiology and function. This review summarizes phenotypic markers that mirror the unique physiology and function of NP cells and their progenitors and should be considered to when measuring outcomes of cell-based therapies to treat disc degeneration.

Figure 1

Decrease of Tie2+ NP cells with ageing and degeneration. Human NP cells donated by patients were studied together with their clinical profiles. Cells were freshly dispersed and only cells detected by flow cytometry within the live and the PI-negative gate were analysed. (a) Representative flow cytometry data of Tie2 and GD2 cell positivity in different age groups. (b) The frequency of Tie2+ cells (T/sp and TG/dp hNP cells) began to decrease before 20 years of age and correlated negatively with age (n=23, R2=0.9224). (c) The frequency of hNP-CFU-S generation also decreased with age (n=23, R2=0.8665). (d) The frequency of Tie2+ cells (T/sp and TG/dp hNP cells) decreased in relation to the extent of disc degeneration graded by morphology and (e) with disc degeneration graded by diagnostic magnetic resonance imaging (n=11). (f) The frequency of hNP-CFU-S generation decreased in relation to the extent of disc degeneration graded by morphology (n=23). *P<0.05, **P<0.01 (ANOVA with Mann–Whitney U-test). Data are represented as mean±s.d. Adapted from Ref. .

Figure 2

Schematic diagram showing cell based therapy strategy for disc regeneration. Mesenchymal stem cells (MSCs) can be derived from either bone marrow (BM-MSCs) or adipose (AD-MSCs), before undergoing differentiation into NP-like cells through various treatments. Alternately, NP progenitor cells may be identified with markers and isolated directly from healthy disc tissue. Confirmation of NP cell phenotype as defined by functional, tissue-of-origin, and other markers unique to NP cells before transplantation is necessary for successful disc regeneration.