Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration.

Giovanni Marfia,Matteo Figini,Clara Di Vito,Giulio Alessandri,Laura Riboni,Eugenio Parati,Alessandro Scotti,Stefania Elena Navone,Ileana Zucca,Rolando Campanella

doi:10.1186/s13075-014-0457-5

Abstract

IntroductionBiglycan is an important proteoglycan of the extracellular matrix of intervertebral disc (IVD), and its decrease with aging has been correlated with IVD degeneration. Biglycan deficient (Bgn−/0) mice lack this protein and undergo spontaneous IVD degeneration with aging, thus representing a valuable in vivo model for preliminary studies on therapies for human progressive IVD degeneration. The purpose of the present study was to assess the possible beneficial effects of adipose-derived stromal cells (ADSCs) implants in the Bgn−/0 mouse model.MethodsTo evaluate ADSC implant efficacy, Bgn−/0 mice were intradiscally (L1-L2) injected with 8x104 ADSCs at 16 months old, when mice exhibit severe and complete IVD degeneration, evident on both 7Tesla Magnetic Resonance Imaging (7TMRI) and histology. Placebo and ADSCs treated Bgn−/0 mice were assessed by 7TMRI analysis up to 12 weeks post-transplantation. Mice were then sacrificed and implanted discs were analyzed by histology and immunohistochemistry for the presence of human cells and for the expression of biglycan and aggrecan in the IVD area.ResultsAfter in vivo treatment, 7TMRI revealed evident increase in signal intensity within the discs of mice that received ADSCs, while placebo treatment did not show any variation. Ultrastructural analyses demonstrated that human ADSC survival occurred in the injected discs up to 12 weeks after implant. These cells acquired a positive expression for biglycan, and this proteoglycan was specifically localized in human cells. Moreover, ADSC treatment resulted in a significant increase of aggrecan tissue levels.ConclusionOverall, this work demonstrates that ADSC implant into degenerated disc of Bgn−/0 mice ameliorates disc damage, promotes new expression of biglycan and increased levels of aggrecan. This suggests a potential benefit of ADSC implant in the treatment of chronic degenerative disc disease and prompts further studies in this field.

Highlights

Biglycan is an important proteoglycan of the extracellular matrix of intervertebral disc (IVD), and its decrease with aging has been correlated with IVD degeneration
Overall, this work demonstrates that Human-derived adipose mesenchymal stem cell (ADSC) implant into degenerated disc of biglycan-deficient mice (Bgn−/0) mice ameliorates disc damage, promotes new expression of biglycan and increased levels of aggrecan
The degeneration process was already observed at 11 months and reached maximal degeneration at 16 to 18 months, resulting in a complete hypointense signal, which has been shown to be related to the loss of IVD proteoglycans and water content [26]

Summary

Introduction

Biglycan is an important proteoglycan of the extracellular matrix of intervertebral disc (IVD), and its decrease with aging has been correlated with IVD degeneration. Biglycan deficient (Bgn−/0) mice lack this protein and undergo spontaneous IVD degeneration with aging, representing a valuable in vivo model for preliminary studies on therapies for human progressive IVD degeneration. IVD degeneration has been found to spontaneously occur in biglycan-deficient (Bgn−/0) mice, which represent a valuable in vivo model to study degenerative disc disease [2]. In this animal model, 7-Tesla magnetic resonance imaging (7TMRI) is a noninvasive tool that is able to evaluate pathological evolution over time and therapeutic follow up [10]

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