Migration of bone marrow–derived cells for endogenous repair in a new tail-looping disc degeneration model in the mouse: a pilot study

Abstract

Background contextMobilization and homing of bone marrow–derived cells (BMCs) play a pivotal role in healing and regeneration of various tissues. However, the cellular response of BMCs in avascular tissue such as the intervertebral disc (IVD) has not been studied in detail. One of the main obstacles to this is a lack of a suitable mouse disc degeneration model. PurposeThe purpose of this study was to establish a reproducible disc degeneration mouse model suitable for analyzing the cellular response of the disc microenvironment and to determine whether BMCs are recruited into the IVD. Study designAn experimental animal study of disc degeneration investigating the potential of BMCs in an endogenous repair of the IVD. MethodsWe transplanted whole bone marrow cells from mice ubiquitously expressing enhanced green fluorescent protein into lethally irradiated mice. Intervertebral disc degeneration was induced through uneven loading by creating a loop in the tail of these mice. The vertebral bone-disc-vertebral bone units were harvested, and BMCs were identified by immunohistochemistry. ResultsA new disc degeneration model was established in the mouse. Applying this model in the bone marrow chimeric mice increased the number of BMCs in the peripheral bone marrow and vascular canals in the endplate, and some were found in the IVD. The migration of BMCs was related to the severity of IVD degeneration. ConclusionsAlthough providing a new disc degeneration model in mice, the present study provides evidence to suggest that although BMCs are recruited during disc degeneration, only a limited number of BMCs migrate to the IVD, presumably because of its avascular nature. This fact provides important elements for developing new treatments as many growth factors and compounds are being tested, both in investigational levels and clinical trials to nourish resident endogenous cells during the degenerative process.