Safe nanoengineering and incorporation of transplant populations in a neurosurgical grade biomaterial, DuraGen PlusTM, for protected cell therapy applications

Finch, Louise; Harris, Sarah; Solomou, Georgios; Sen, Jon; Tzerakis, Nikolaos; Emes, Richard D.; Lane, Catherine S.; Hart, Sarah R.; Adams, Christopher F.; Chari, Divya M.

Abstract

High transplant cell loss is a major barrier to translation of stem cell therapy for pathologies of the brain and spinal cord. Encapsulated delivery of stem cells in biomaterials for cell therapy is gaining popularity but experimental research has overwhelmingly used laboratory grade materials unsuitable for human clinical use - representing a further barrier to clinical translation. A potential solution is to use neurosurgical grade materials routinely used in clinical protocols which have an established human safety profile. Here, we tested the ability of Duragen Plus™ - a clinical biomaterial used widely in neurosurgical duraplasty procedures, to support the growth and differentiation of neural stem cells- a major transplant population being tested in clinical trials for neurological pathology. Genetic engineering of stem cells yields augmented therapeutic cells, so we further tested the ability of the Duragen Plus™ matrix to support stem cells engineered using magnetofection technology and minicircle DNA vectors- a promising cell engineering approach we previously reported (Journal of Controlled Release, 2016 a \&b). The safety of the nano-engineering approach was analysed for the first time using sophisticated data-independent analysis by mass spectrometry-based proteomics. We prove that the Duragen Plus™ matrix is a promising biomaterial for delivery of stem cell transplant populations, with no adverse effects on key regenerative parameters. This advanced cellular construct based on a combinatorial nano-engineering and biomaterial encapsulation approach, could therefore offer key advantages for clinical translation.

Citation

Finch, L., Harris, S., Solomou, G., Sen, J., Tzerakis, N., Emes, R. D., …Chari, D. M. (2020). Safe nanoengineering and incorporation of transplant populations in a neurosurgical grade biomaterial, DuraGen PlusTM, for protected cell therapy applications. Journal of Controlled Release, 321, 553-563. https://doi.org/10.1016/j.jconrel.2020.02.028

• Journal Article Type: Article
• Acceptance Date: Feb 17, 2020
• Online Publication Date: Feb 19, 2020
• Publication Date: May 10, 2020
• Journal: Journal of Controlled Release
• Print ISSN: 0168-3659
• Electronic ISSN: 1873-4995
• Publisher: Elsevier
• Volume: 321
• Pages: 553-563
• DOI: https://doi.org/10.1016/j.jconrel.2020.02.028
• Keywords: Biomaterial, Combinatorial therapy, DNA minicircles, Genetic engineering, Magnetofection, Mass spectrometry, Neural stem cell, Proteomics, SWATH, Biocompatible Materials, Cell Differentiation, DNA, Humans, Neural Stem Cells, Stem Cell Transplantation, Tis
• Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/32087299