The traceability of mesenchymal stromal cells after injection into degenerated discs in patients with low back pain.

Low back pain is a major health issue and one main cause to this condition is believed to be intervertebral disc (IVD) degeneration. Stem cell therapy for degenerated discs using mesenchymal stromal cells (MSCs) has been suggested. The aim of the study was to investigate presence and distribution pattern of autologous MSCs transplanted into degenerated IVDs in patients and explanted post transplantation. IVD tissues from 4 patients (41,45, 47 and 47 years of age) participating in a clinical feasibility study on MSC transplantation to degenerative discs were investigated. Three patients decided to undergo fusion surgery at time-points 8 months and one patient at 28 months post transplantation. Pre-transplantation, MSCs from bone marrow aspirate, MSCs were isolated by centrifugation, FICOLL®-test-tubes and cultured (passage 1). Before transplantation, MSCs were labeled with 1 mg/mL iron-sucrose (Venofer®) and 1X106 MSCs were transplanted into degenerated IVDs. At the time-point of surgery, IVD tissues were collected. IVD tissue samples were fixated, embedded in paraffin and sections prepared. IVD samples were stained with Preussian blue which visualize iron deposits and examined (light microscopy). Immunohistochemistry (IHC) including SOX9, Coll2A1 and cell viability (TUNEL was performed. Cells positive for iron deposits were observed in IVD tissues (3/4 patients). The cells/iron deposits were observed in clusters and/or as solitary cells in regions in IVD tissue samples (ROIs). By IHC, SOX9 and Coll2A1 positive cells were detected in the same regions as detected cells/iron deposits. A few non-viable cells were detected by TUNEL assay in ROIs. Results demonstrated that MSCs, labelled with iron sucrose, transplanted into degenerated IVDs were detectable 8 months post transplantation. The detected cellular activity indicates that MSCs have differentiated into chondrocyte-like cells and that the injected MSCs and/or their progeny have survived since the cells were found in large cluster and as solitary cells which were distributed at different parts of the IVD.

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