Autologous fibroblasts induce fibrosis of the nucleus pulposus to maintain the stability of degenerative intervertebral discs

Abstract

Lumbar degenerative disc diseases cause low back pain (LBP). The maintenance of the height and stability of the intervertebral disc (IVD) space is an effective treatment for LBP. The following study evaluated the effects of fibroblast injection on intervertebral disc degeneration (IDD) in a preclinical setting. Compared with the IDD group, the fibroblast treatment group demonstrated effective maintenance of IVD height, reduced endplate degeneration, and improved nuclear magnetic resonance signals and overall histological structure. In doing so, fibrotic IVDs maintained the stability and biomechanics of the vertebra. This finding is in agreement with clinical findings that human nucleus pulposus (NP) fibrosis is essential for the maintenance of IVD height and mechanical properties in patients following percutaneous endoscopic lumbar discectomy (PELD). Mechanistically, we demonstrated that injected fibroblasts not only proliferated but also induced NP cells to adopt a fibrotic phenotype via the secretion of TGF-β. Finally, to better mimic human conditions, the efficacy of autologous fibroblast injection in the treatment of IDD was further examined in a nonhuman primate cynomolgus monkey model due to their capacity for upright posture. We showed that the injection of fibroblasts could maintain the IVD height and rescue IVD signals in cynomolgus monkeys. Taken together, the results of our study reveal that autologous fibroblast injection can enhance the natural process of fibrosis during acute and subacute stages of stress-induced IDD. Fibrotic IVDs can maintain the stability, biological activity, and mechanical properties of the intervertebral space, thus providing a new direction for the treatment of intervertebral space-derived lumbar degenerative diseases.

Bleomycin induces fibrotic transformation of bone marrow stromal cells to treat height loss of intervertebral disc through the TGFβR1/Smad2/3 pathway

“…BMSCs was induced to acquire brotic phenotype by Bleomycin in vitro Our previous research using a cell-based approach have shown that induction of reparative brosis may offer bene cial effects against the progression of disc degeneration [17], and this process is associated with TGFβ signaling pathway. Considering the Bleomycin is an effective trigger to induce the upregulation of TGFβ in lung epithelium cells [24] and have been used in clinical situation before , we tried to use bleomycin combined with the multipotentiality of BMCSs to induce their brotic differentiation.…”

“…Moreover, recent researches have unveiled that there are some MSCs distributed around the outer AF region and endplate [16]. So from a different perspective that a former approach of our studies by injection of autologous dermal broblast cells into degenerative intervertebral to treat IVDD [17]: We showed that the induction of reparative brosis combined with two essential cells in discs, one is to induce the brotic phenotype of MSCs, and the other is to promote the broblastic-like cell AF cells.…”

Bleomycin Induces Fibrotic Transformation of Bone Marrow Stromal Cells to Treat Height Loss of Intervertebral Disc Through the TGFβR1/Smad2/3 Pathway

“…BMSCs was induced to acquire brotic phenotype by Bleomycin in vitro Our previous research using a cell-based approach have shown that induction of reparative brosis may offer bene cial effects against the progression of disc degeneration [20], and this process is associated with TGFβ signaling pathway. Considering the Bleomycin is an effective trigger to induce the upregulation of TGFβ in lung epithelium cells [26] and have been used in clinical situation before , we tried to use bleomycin combined with the multipotentiality of BMCSs to induce their brotic differentiation.…”

“…Moreover, recent researches have unveiled that there are some MSCs distributed around the outer AF region and endplate [19]. So from a different perspective that a former approach of our studies by injection of autologous dermal broblast cells into degenerative intervertebral to treat IVDD [20]: We showed that the induction of reparative brosis combined with two essential cells in discs, one is to induce the brotic phenotype of MSCs, and the other is to promote the broblastic-like cell AF cells.…”

“…Hence from our perspective, we advocate to activate the MSCs and broblast-like cells, promote its ability of migration and collagen deposition aiming at nally alternate the declining NP tissues and successfully maintain even restore the disc height .The induction of reparative and fast brosis in degenerative intervertebral discs could offer a way for tissue repair and spine stabilization. We and others have previously shown that reparative brosis de ne here as the formation of organized scar tissue necessary to mechanically stabilize the degenerative intervertebral disc, have potential bene cial effects against the height loss during intervertebral disc degeneration [20,38]. The use of dermal broblast-based cell therapy was found to induce degenerative intervertebral disc brosis, prevent the loss of disc height and disc collapse, and maintain the biomechanical properties of the spine [39,40].…”