title: Human annulus progenitor cells: Analyses of this viable endogenous cell population.
abstract: Back pain and intervertebral disc degeneration have growing socioeconomic/health care impacts. Increasing research efforts address use of stem and progenitor cell-based replacement therapies to repopulate and regenerate the disc. Data presented here on the innate human annulus progenitor cells: (i) assessed osteogenic, chondrogenic and adipogenic potentials of cultured human annulus cells; and (ii) defined progenitor-cell related gene expression patterns. Verification of the presence of progenitor cells within primary human disc tissue also used immunohistochemical identification of cell surface markers and microarray analyses. Differentiation analysis in cell cultures demonstrated a viable progenitor cell pool within Thompson grades III-IV discs. Osteogenesis was present in 8 out of 11 cultures (73%), chondrogenesis in 8 of 11 (73%), and adipogenesis in 6 of 6 (100%). Immunolocalization was positive for CD29, CD44, CD105, and CD14 (mean values 80.2%, 81.5%, 85.1%, and 88.6%, respectively); localization of CD45 and CD34 was negative in disc tissue. Compared to controls, surgical discs showed significantly downregulated genes with recognized progenitor cell functions: TCF7L2 (2.7 fold), BMI1 (3.8 fold), FGF receptor 2 (2 fold), PAFAH1B1 (2.3 fold), and GSTP1 (9 fold). Compared to healthier grade I/II discs, grade III/IV discs showed significantly upregulated XRCC5 (3.6 fold), TCF7L2 (6 fold), GSTP1 (3.7 fold), and BMI1 (3 fold). Additional significant cell marker analyses showed expression of platelet-derived growth factor receptor alpha, CD90, CD73, and STRO-1. Statement of Clinical Significance: Findings provide the first identification of progenitor cells in annulus specimens from older, more degenerate discs (in contrast to earlier studies of healthier discs or nondegenerative specimens from teenagers). Findings also increase knowledge on progenitor cells present in the disc and suggest their value in potential future utilization for regeneration and disc cell therapy. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1351-1360, 2016.
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Calorina, 20226.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Gruber
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Calorina, 20226.
authors.forename: Frank E
authors.initials: FE
authors.lastname: Riley
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Calorina, 20226.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Hoelscher
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Calorina, 20226.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Ingram
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Calorina, 20226.
authors.forename: Letitia
authors.initials: L
authors.lastname: Bullock
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Calorina, 20226.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Hanley
mesh_terms: D050156:Adipogenesis; D000328:Adult; D053687:Adult Stem Cells / Q000502:physiology*; D000368:Aged; D000070616:Annulus Fibrosus / Q000166:cytology*; D020219:Chondrogenesis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis
keywords: annulus fibrosus; intervertebral disc; progenitor cell differentiation; progenitor cells; progenitor disc cells