The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: A descriptive study in humans

Sammanfattning

Low back pain is common and degenerated discs 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 degenerated discs(DDs) is important. The aim of the study was to examine presence of local stem-/progenitor cells in human DDs and if these cell-populations could respond to paracrin stimulation in vitro. Tissue biopsies from the IVD region (L3-S1) was collected from 15 patients, age 34-69 years, undergoing surgery (spinal fusion) and mesenchymal stem cells (MSCs)(iliac crest) from two donors. Non-degenerated disc cells were collected from one donor(scoliosis) and chordoma tissue was obtained from(positive control, stem cell markers) two 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 was detected 15/15 samples. Immunohistochemistry analysis supported findings on 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 MSC compared to cell-cultures cultured with conditioned media from non-degenerated disc 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 by paracrin signalling /soluble factors from MSCs and from non-degenerated IVD cells was observed in vitro indicating that repair processes within human degenerated discs may be stimulated.