Therapeutic Effects of Cell Therapy with Neonatal Human Dermal Fibroblasts and Rabbit Dermal Fibroblasts on Disc Degeneration and Inflammation

Publication date: Available online 22 August 2018

Source: The Spine Journal

Author(s): Peng Shi, Ana Chee, Weijun Liu, Po-Hsin Chou, Jun Zhu, Howard S. An

Abstract

Background Context

Increasing evidence suggests transplanting viable cells into the degenerating intervertebral disc (IVD) may be effective in treating disc degeneration and back pain. Clinical studies utilizing autologous or allogeneic mesenchymal stem cells (MSCs) to treat patients with back pain have reported some encouraging results. Animal studies have shown that cells injected into the disc can survive for months and have regenerative effects. Studies to determine the advantages and disadvantages of cell types and sources for therapy are needed.

Purpose

The objective of this study is to determine the impact of donor source on the therapeutic effects of dermal fibroblast treatment on disc degeneration and inflammation.

Study Design

Using the rabbit disc degeneration model, we compared transplantation of neonatal human dermal fibroblasts (nHDFs) and rabbit dermal fibroblasts (RDFs) into rabbit degenerated discs on host immune response, disc height and IVD composition.

Methods

New Zealand white rabbits received an annular puncture using an 18-guage needle to induce disc degeneration. Four weeks after injury, rabbit IVDs were treated with 5 × 10⁶ nHDFs, RDFs or saline. At eight weeks post-treatment, animals were sacrificed. X-ray images were obtained. IVDs were isolated for inflammatory and collagen gene expression analysis using real-time PCR and biochemical analysis of proteoglycan contents using dimethylmethylene blue (DMMB) assay. These studies were funded by a research grant from SpinalCyte, LLC ($414,431).

Results

Eight weeks after treatment, disc height indexes of discs treated with nHDF increased significantly by 7.8% (p<0.01) while those treated with saline or RDF increased by 1.5% and 2.0%, respectively. Gene expression analysis showed that discs transplanted with nHDFs and RDFs displayed similar inflammatory responses (p= 0.2 to 0.8). Compared to intact discs, expression of both collagen types I and II increased significantly in nHDF-treated discs (p<0.05), trending to significant in RDF-treated discs, and not significantly in saline treated discs. The ratio of collagen type II/ collagen type I was higher in the IVDs treated with nHDFs (1.26) than those treated with RDFs (0.81) or saline (0.59) and intact discs (1.00). Lastly, proteoglycan contents increased significantly in discs treated with nHDF (p<0.05) and were trending towards significance in the RDF-treated discs compared to those treated with saline.

Conclusions

This study showed that cell transplantation with nHDF into degenerated IVDs can significantly increase markers of disc regeneration (disc height, collagen type I and II gene expression, and proteoglycan contents). Transplantation with RDFs showed similar regenerative trends but these trends were not significant. This study also showed that the human cells transplanted into the rabbit discs did not induce a higher immune response than the rabbit cells. These results support that the intervertebral disc is immune privileged and would tolerate allogeneic or xenogeneic grafts.

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