Can Stem Cells Home to the Injured Intervertebral Disk Via Intravenous Infusion? A Murine Model

Introduction Patients who suffer traumatic injury of the spine can also present with intervertebral disk injury, both of which are associated with low back pain (LBP). While conventional treatments mainly serve to alleviate pain, these treatments are not biological. Various biological therapies such as growth hormones/factors and cells have been studied for treatment of different conditions including that of IVD degeneration, which is also associated with LBP. In various animal models, such biological therapies have been demonstrated to slow or even reverse degeneration. 1,2 The use of stem cells to treat injury is very promising due to their ability to regenerate and differentiate into other cell types—thus lies their potential to repair tissue damage. Of great interest is a population of cord-blood stem cells with expanded multipotency and mesenchymal stem cell (MSC)-like properties. 3 These cells are reported to home to injured sites after intravenous (IV) injection and are demonstrated in a rat spinal cord injury model to induce beneficial effects to injured rats. 4 The use of such homing stem cells is advantageous as this could potentially bypass invasive surgery. We investigated the potential of these stem cells to aid IVD repair by determining (1) if these cells could home to injured IVD after intravenous infusion and (2) induce any beneficial effects on the morphology of the injured IVD using a murine model of IVD disk injury. Materials and Methods Stem cells were isolated from human umbilical cord blood as previously reported. 3 Animal ethics was approved by the CULATR at the University of HK, and NOD/SCID mice aged 6–8 weeks (5/group) were used. Mice were anaesthetized and X-rayed to identify the caudal disk levels to be punctured and unpunctured controls. A 31G needle was used to perpendicularly puncture disks, the wounds were sutured and mice underwent standard postoperative procedures. On the day of puncture or 1 week postpuncture, cells were thawed and resuspended in DMEM and injected via the tail vein (10E6). IVDs were harvested at 7 days or 1 month postcell injection and processed for histology. IVD morphology was visualized with the FAST staining method. 5 Stem cells were tracked by staining for antihuman mitochondrial antibodies. Results From the FAST staining, the IVD morphology was disrupted after puncture of the disk with a large loss of cells from the NP and the loss of the AF/NP border (Figs. 1 and 2). Little difference in morphology of the disks were observed between groups with cells injected versus no cells injected after 1 month (Fig. 2), however, both yielded similar staining intensity of the NP matrix. Immunostaining for the stem cells indicated that few cells migrated to the punctured disk. In the sections that did yield cells, they were usually single cells and found in the growth plate area or adjacent to the EP blood vessels, but not in the NP or AF. Cells were also found in adjacent unpunctured disks, and also in other organs including the spleen and lungs. Conclusion The intravenous introduction of the stem cells did not arrest degeneration nor regenerate the IVD after 1 month. Few cells were found to be located at the sites of puncture, and of the cells that were found, these were limited to the growth plate area or vessels around the end plate, but not in the NP or AF. It is possible that the little change in morphology of the IVD, after 1 month of injury and intravenous introduction of the stem cells, was due to the fact that few cells were able to migrate to the injured disk. This may have been caused by a number of factors including: (1) the homing signal that was not sufficient to attract the stem cells to the injured site, (2) the avascular nature of the IVD which further limited cell penetration to the injured site, and (3) that the cells lodged in other organs such as the lungs and spleen. Ongoing studies are being carried out to quantitatively determine any localized changes to the IVD including proteoglycan and gene expression levels. This work is supported by the Seed Funding Programme for Basic Research, The University of Hong Kong. I confirm having declared any potential conflict of interest for all authors listed on this abstract No Disclosure of Interest None declared Ho G, et al. Connective Tissue Research 2008;49(1):15–21 Yang F, et al. Molecular Therapy 2009;17(11):1959–1966 Rogers I, et al. Experimental Cell Research 2007;313(9):1839–1852 Chua SJ, et al. Spine (Phila Pa 1976), 2010;35(16):1520–1526 Leung VY, et al. Journal of Histochemical Cytochemistry 2009;57(3):249–256

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