Characterization of mesenchymal stromal cell-mediated mitochondrial transfer to healthy and diseased intervertebral disc cells

Intradiscal injection of mesenchymal stromal cells has gained widespread interest for the treatment of intervertebral disc degeneration. Mesenchymal stromal cells have been shown to impart a therapeutic benefit on treated tissues through a variety of mechanisms including mitochondrial transfer. Mitochondrial transfer from mesenchymal stromal cells to diseased cells has been demonstrated, in numerous model systems, to increase the survival and function of recipient cells. To date there are few studies that have investigated mitochondrial transfer from mesenchymal stromal cells to intervertebral disc cells. The goal of this study is to characterize mitochondrial transfer from mesenchymal stromal cells to bovine and human intervertebral disc cells using confocal microscopy. Following a 24-hour coculture period, bovine mesenchymal stromal cells were shown to transfer mitochondria to bovine annulus fibrosus cells under both healthy and inflammatory conditions. In addition, human mesenchymal stromal cells were shown to transfer mitochondria to diseased, patient-derived intervertebral disc cells. Mitochondrial transfer quantity was found to increase under inflammatory stress conditions and with patient age, though functional consequences of this transfer remain to be determined. This study is the first to show mesenchymal stromal cells transfer mitochondria to bovine annulus fibrosus cells and patient derived intervertebral disc cells. We provide evidence that mitochondrial transfer is a relevant mechanism by which mesenchymal stromal cells communicate with intervertebral disc cells.