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

JOURNAL OF CONTROLLED RELEASE

卷:321

Article

Finch, Louise¹  Harris, Sarah⁶  Solomou, Georgios¹  Sen, Jon¹  Tzerakis, Nikolaos²  Emes, Richard D.^3,4  Lane, Catherine S.⁵  Hart, Sarah R.¹  Adams, Christopher F.⁶  Chari, Divya M.¹ 

[1] Keele Univ, Sch Med, Stoke On Trent ST5 5BG, Staffs, England

[2] Univ Hosp North Midlands, Neurosurg Dept, Stoke On Trent ST4 6QG, Staffs, England

[3] Univ Nottingham, Adv Data Anal Ctr, Loughborough LE12 5RD, Leics, England

[4] Univ Nottingham, Sch Vet Med & Sci, Loughborough LE12 5RD, Leics, England

[5] SCIEX Ltd, Phoenix House,Lakeside Dr,Ctr Pk, Warrington WA1 1RX, Cheshire, England

[6] Keele Univ, Fac Nat Sci, Stoke On Trent ST5 5BG, Staffs, England

关键词: Neural stem cell;    Biomaterial;    Combinatorial therapy;    Genetic engineering;    Magnetofection;    DNA minicircles;    Mass spectrometry;    SWATH;    Proteomics;   

DOI  :  10.1016/j.jconrel.2020.02.028

来源: Elsevier

【 摘 要 】

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 (TM)- 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 (TM) 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 (TM) 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.

【 授权许可】

Free