Decellularization technology in CNS tissue repair

Abstract

Decellularization methodologies have been successfully used in a variety of tissue engineering and regenerative technologies and methods of decellularization have been developed for target tissues and organs of interest. The technology to promote regeneration and functional recovery in the CNS, including brain and spinal cord, has, however, made slow progress mainly because the intrinsic regenerative potential of the CNS is regarded as low. To date, currently available therapies have been unable to provide significant functional recovery and successful therapies, which could provide functional restoration to the injured brain and spinal cord are controversial. In this review, the authors provide a critical analysis, comparing the advantages and limitations of the major decellularization methods and considering the effects of these methods upon the biologic scaffold material. The authors also review studies that supplement decellularized grafts with exogenous factors, such as stem cells and growth factors, to both promote and enhance regeneration through decellularized allografts.

Keywords:

• CNS
• decellularization methods
• extracellular matrices
• stem cell
• tissue repair

Acknowledgements

This work was supported by grants from the Scientific Research Foundation of Wenzhou, Zhejiang Province, China (H20090014, Y20090269), Health Bureau of Zhejiang Province (2010KYB070), Research Foundation of Education Bureau of Zhejiang Province (Y201009942), Fresh Talent Program for Science and Technology Wenzhou Medical University (wyx201401011, wyx201401087, wyx201401009 and wyx201401085), Research Funds for Tian Qing Liver Diseases (TQGB20120057) and Project of New Century 551 Talent Nurturing in Wenzhou.

Financial & competing interests disclosure

M Braddock from AstraZenecka R&D provided writing assistance. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Many different types of combination methods have been used to decellularize CNS tissue. The results are variable and some of these methods, for example, enzymatic methods, appear associated with poor quality scaffold preparation.

• Substantial numbers of experimental studies have shown that the extracellular matrices scaffolds may act as supportive factors for accelerating and enhancing SC growth and nerve regeneration after fiber tract injury.

• Many studies that have investigated the use of extracellular matrices in nerve regeneration produce positive results, but further carefully controlled studies are needed to find the optimum treatment and techniques for nerve regeneration.

• Decellularization methods have been employed to partially improve the function of rats with fiber tract injury. Future research should aim to improve the experimental methods, the use of extracellular matrices, and provide more evidence that allow translation of this methodology into clinical assessment.