Differentiation of MSC and annulus fibrosus cells on genetically-engineered silk fleece-membrane-composites enriched for GDF-6 or TGF-β3.

Frauchiger, Daniela Angelika; Heeb, Silvan Rolf; May, Rahel Deborah; Wöltje, Michael; Benneker, Lorin Michael; Gantenbein, Benjamin (2018). Differentiation of MSC and annulus fibrosus cells on genetically-engineered silk fleece-membrane-composites enriched for GDF-6 or TGF-β3. Journal of orthopaedic research, 36(5), pp. 1324-1333. Wiley 10.1002/jor.23778

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Intervertebral disc (IVD) repair is a high-priority topic in our active and increasingly ageing society. Since a high number of people are affected by low back pain treatment options that are able to restore the biological function of the IVD are highly warranted. Here, we investigated whether the feasibility of genetically-engineered (GE)-silk from Bombyx mori containing specific growth factors to precondition human bone-marrow derived mesenchymal stem cells (hMSC) or to activate differentiated human annulus fibrosus cells (hAFC) prior transplantation or for direct repair on the IVD. Here, we tested the hypothesis that GE-silk fleece can thrive human hMSC towards an IVD-like phenotype. We aimed to demonstrate a possible translational application of good manufacturing practice (GMP)-compliant GE-silk scaffolds in IVD repair and regeneration. GE-silk with growth and differentiation factor 6 (GDF-6-silk) or transforming growth factor β3 (TGF-β3, TGF-β3-silk) and untreated silk (cSilk) were investigated by DNA content, cell activity assay and glycosaminoglycan (GAG) content and their differentiation potential by qPCR analysis. We found that all silk types demonstrated a very high biocompatibility for both cell types, i.e., hMSC and hAFC, as revealed by cell activity, and DNA proliferation assay. Further, analyzing qPCR of marker genes revealed a trend to differentiation towards an NP-like phenotype looking at the Aggrecan/Collagen 2 ratio which was around 10:1. Our results support the conclusion that our GE-silk scaffold treatment approach can thrive hMSC towards a more IVD-like phenotype or can maintain the phenotype of native hAFC. This article is protected by copyright. All rights reserved.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute for Surgical Technology & Biomechanics ISTB
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Frauchiger, Daniela Angelika; Heeb, Silvan Rolf; May, Rahel; Benneker, Lorin Michael and Gantenbein, Benjamin

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0736-0266

Publisher:

Wiley

Language:

English

Submitter:

Daniela Angelika Frauchiger

Date Deposited:

18 Jan 2018 17:14

Last Modified:

23 Nov 2018 02:30

Publisher DOI:

10.1002/jor.23778

PubMed ID:

29058815

Uncontrolled Keywords:

Silk bone morphogenic protein 13 growth and differentiation factor 6 intervertebral disc transforming growth factor β3

BORIS DOI:

10.7892/boris.106552

URI:

https://boris.unibe.ch/id/eprint/106552

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