Abstract
Intervertebral disc (IVD) degeneration is one of the predominant causes of chronic low back pain (LBP), which is a leading cause of disability worldwide. Despite substantial progress in cell therapy for the treatment of IVD degeneration, significant challenges remain for clinical application. Here, we investigated the effectiveness of hyaluronan–methylcellulose (HAMC) hydrogels loaded with Wharton’s Jelly-derived mesenchymal stromal cell (WJ-MSCs) in vitro and in a rat coccygeal IVD degeneration model. Following induction of injury-induced IVD degeneration, female Sprague-Dawley rats were randomized into four groups to undergo a single intradiscal injection of the following: (1) phosphate buffered saline (PBS) vehicle, (2) HAMC, (3) WJ-MSCs (2 × 104 cells), and (4) WJ-MSCs-loaded HAMC (WJ-MSCs/HAMC) (n = 10/each group). Coccygeal discs were removed following sacrifice 6 weeks after implantation for radiologic and histologic analysis. We confirmed previous findings that encapsulation in HAMC increases the viability of WJ-MSCs for disc repair. The HAMC gel maintained significant cell viability in vitro. In addition, combined implantation of WJ-MSCs and HAMC significantly promoted degenerative disc repair compared to WJ-MSCs alone, presumably by improving nucleus pulposus cells viability and decreasing extracellular matrix degradation. Our results suggest that WJ-MSCs-loaded HAMC promotes IVD repair more effectively than cell injection alone and supports the potential clinical use of HAMC for cell delivery to arrest IVD degeneration or to promote IVD regeneration.
Highlights
Chronic low back pain (LBP) is the leading cause of disability worldwide and the social and economic impact is enormous [1]
We found that combined injection of HAMC and Wharton’s Jelly-derived mesenchymal stromal cell (WJ-mesenchymal stromal cells (MSCs)) significantly diminished the expression of matrix-degrading enzyme, matrix metalloproteinases (MMPs)-13
We investigated the influence of HAMC on cell survival in vitro and thein vivo effects of HAMC loaded with WJ-MSCs in a rat model of intravertebral disc (IVD) degeneration to test potential clinical usability of HAMC for cell delivery
Summary
Chronic low back pain (LBP) is the leading cause of disability worldwide and the social and economic impact is enormous [1]. As the stage of degeneration progresses, the production of pro-inflammatory molecules, including tumor necrosis factor (TNF)-α, interferon gamma (IFN-γ), and interleukin (IL-1β, IL-6, IL-1α and IL-2) increases [5]. These molecules can be produced by both IVD cells and immune cells, such as macrophages [6], and are known to be associated with discogenic back pain [6]. There is a strong clinical demand for the development of regenerative therapy to repair degenerated disc or arrest IVD degeneration at earlier stages [1,4]. Several clinical studies on IVD cell therapies reported that MSC implantation can regenerate the degenerated disc and cure discogenic back pain [5,12]
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