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Acta Biomater. 2019 Mar 1;86:300-311. doi: 10.1016/j.actbio.2019.01.028. Epub 2019 Jan 17.

Sustained release of GDF5 from a designed coacervate attenuates disc degeneration in a rat model.

Author information

1
Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, #88, Jiefang Road, Hangzhou 310009, PR China.
2
Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou 310009, Zhejiang, PR China.
3
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, International Joint Laboratory for Advanced Fiber and Low-dimension Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, P.R. China.
4
Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, #88, Jiefang Road, Hangzhou 310009, PR China. Electronic address: lifangcai@zju.edu.cn.
5
Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, #88, Jiefang Road, Hangzhou 310009, PR China. Electronic address: huimintao@zju.edu.cn.
6
Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jie Fang Road, Hangzhou 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, #88, Jiefang Road, Hangzhou 310009, PR China. Electronic address: liangchengzhen@zju.edu.cn.

Abstract

Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF5) can differentiate into an NP-like phenotype. Although stem cell-based therapy with prolonged exposure to growth factors is regarded as a promising treatment, the efficacy of this approach in attenuating the disc degeneration process is limited by the short lifespan of growth factors. In our study, a unique growth factor delivery vehicle composed of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride) (PEAD) was used to sustain GDF5 release. The results showed that sustained release of GDF5 by the PEAD:heparin delivery system promoted hADSC differentiation to an NP-like phenotype in vitro. After injection of the PEAD:heparin:GDF5 delivery platform and hADSCs into intervertebral spaces of coccygeal (Co) vertebrae Co7/Co8 and Co8/Co9 of the rat, the disc height, water content, and structure of the NPs decreased more slowly than other treatment groups. This new strategy may be used as an alternative treatment for attenuating intervertebral disc degeneration with hADSCs without the need for gene therapy. STATEMENT OF SIGNIFICANCE: Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF-5) can differentiate into an NP-like phenotype. Although stem cell-based therapy with prolonged exposure to growth factor is regarded as a promising treatment, the efficacy of this approach in the disc regeneration process is limited by the short life of growth factors. In our study, a unique growth factor delivery vehicle comprised of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride) (PEAD) was used to sustain the release of GDF-5. Numerous groups have explored IDD regeneration methods in vitro and in vivo. Our study differs in that GDF5 was incorporated into a vehicle through charge attraction and exhibited a sustained release profile. Moreover, GDF-5 seeded coacervate combined with hADSC injection could be a minimally invasive approach for tissue engineering that is suitable for clinical application. We investigated the stimulatory effects of our GDF-5 seeded coacervate on the differentiation of ADSCs in vitro and the reparative effect of the delivery system on degenerated NP in vivo.

KEYWORDS:

Differentiation; Growth factor therapy; Heparin; Human adipose-derived stem cells; Intervertebral disc; Stem cell transplantation

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