title: The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: a descriptive study in humans.
abstract: Low back pain is common and degenerated discs (DDs) are believed to be a major cause. In non-degenerated intervertebral discs (IVDs) presence of stem/progenitor cells was recently reported in different mammals (rabbit, rat, pig). Understanding processes of disc degeneration and regenerative mechanisms within DDs is important. The aim of the study was to examine the presence of local stem/progenitor cells in human DDs and if these cell populations could respond to paracrine stimulation in vitro. Tissue biopsies from the IVD region (L3-S1) were collected from 15 patients, age 34-69 years, undergoing surgery (spinal fusion) and mesenchymal stem cells (MSCs) (iliac crest) from 2 donors. Non-DD cells were collected from 1 donor (scoliosis) and chordoma tissue was obtained from (positive control, stem cell markers) 2 donors. The IVD biopsies were investigated for gene and protein expression of: OCT3/4, CD105, CD90, STRO-1, and NOTCH1. DD cell cultures (pellet mass) were performed with conditioned media from MSCs and non-degenerated IVD cells. Pellets were investigated after 7, 14, 28 days for the same stem cell markers as above. Gene expression of OCT3/4 and STRO-1 was detected in 13/15 patient samples, CD105 in 14/15 samples, and CD90 and NOTCH1 were detected 15/15 samples. Immunohistochemistry analysis supported findings on the protein level, in cells sparsely distributed in DDs tissues. DDs cell cultures displayed more undifferentiated appearance with increased expression of CD105, CD90, STRO-1, OCT3/4, NOTCH1, and JAGGED1, which was observed when cultured in conditioned cell culture media from MSCs compared to cell cultures cultured with conditioned media from non-DD cells. Expression of OCT3/4 (multipotency marker) and NOTCH1 (regulator of cell fate), MSC-markers, CD105, CD90, and STRO-1, indicate that primitive cell populations are present within DDs. Furthermore, the possibility to influence cells from DDs by paracrine signaling /soluble factors from MSCs and from nondegenerated IVD cells was observed in vitro indicating that repair processes within human DDs may be stimulated.
authors.affiliation: Department of Orthopaedics, Institute of Clinical Sciences, Gothenburg University, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Brisby
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papadimitriou
authors.forename: Camilla
authors.initials: C
authors.lastname: Brantsing
authors.forename: Peter
authors.initials: P
authors.lastname: Bergh
authors.forename: Anders
authors.initials: A
authors.lastname: Lindahl
authors.forename: Helena
authors.initials: H
authors.lastname: Barreto Henriksson
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D000954:Antigens, Surface / Q000096:biosynthesis; D015415:Biomarkers / Q000032:analysis*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D000071063:Endoglin; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000473:pathology*; D000072100:Jagged-1 Protein; D017116:Low Back Pain / Q000209:etiology; D008565:Membrane Proteins / Q000096:biosynthesis; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008875:Middle Aged; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D019899:Paracrine Communication; D051881:Receptor, Notch1 / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D000072099:Serrate-Jagged Proteins; D013123:Spinal Fusion; D013131:Spine / Q000166:cytology / Q000601:surgery; D018800:Thy-1 Antigens / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D015415:Biomarkers; D002135:Calcium-Binding Proteins; C064206:ENG protein, human; D000071063:Endoglin; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; C525591:STRO-1 antigen, human; D000072099:Serrate-Jagged Proteins; D018800:Thy-1 Antigens