Abstract
The human amniotic membrane (hAM) is an attractive biomaterial for regenerative medicine, as it contains amniotic mesenchymal stromal cells (hAMSC), epithelial cells (hAEC) and growth factors. We examined the potential use of hAM in orthopaedic and maxillofacial bone surgery, integrating the requirements of current regulations regarding advanced therapy medicinal products (ATMP) in the European Union. Previous studies have described the potential osteodifferentiation of intact hAM during whole-tissue culture in osteogenic conditions. The present study aims to determine whether in vitro osteodifferentiation of hAM is needed in the context bone repair, and the influence of this process on tissue structure, cell phenotype and cell function. Different conditions (fresh or cultured hAM; intact or hAM-derived cells) were tested. Phenotypic and functional analyses were performed with standard approaches (cell culture and staining, histological and immunolabelling) as well as original approaches (tissue staining, energy dispersive X-ray and X-ray diffraction). In our study, non-osteodifferentiated hAM (i.e., fresh or native hAM) exhibited innate pre-osteoblastic potential. Osteodifferentiation of fresh hAM induced a change in tissue structure, cell phenotype and function. Therefore, we hypothesize that pre-osteodifferentiation may not be necessary, especially if it induces unwanted changes. To our surprise, in these osteogenic conditions, hAEC had a mesenchymal phenotype with osteocyte function, and even native synthesis of hydroxyapatite, focusing osteogenic potential mainly in this epithelial layer. In conclusion, in vitro osteodifferentiation by tissue culture does not appear to be necessary for hAM to be used as an innovative ATMP for bone repair.
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Acknowledgements
We thank Prof. Narcisse Zwetyenga (Department of Maxillofacial Surgery, Plastic - Reconstructive and Aesthetic Surgery, Hand Surgery, University Hospital Dijon, France) for his involvement in this study. Thanks to Prof. Ornella Parolini (Istituto di Anatomia e Biologia Cellulare, Università Cattolica del Sacro Cuore, Roma), Drs Susanne Wolbank and Andrea Lindenmair (Ludwig Boltzmann Inst. for Exp. and Clinical Traumatology, Linz, Austria) and Simone Hennerbichler (Red Cross Transfusion Center, Linz, Austria) for their technical advice. The authors thank Fiona Ecarnot (EA3920, University Hospital Besançon, France) and Joanne Archambault, PhD for editorial assistance. This work contributes to the COST Action CA17116 “International Network for Translating Research on Perinatal Derivatives into Therapeutic Approaches (SPRINT)”, supported by COST (European Cooperation in Science and Technology).
Funding
This study was funded by the Région of Franche-Comté, France (No. 2013 C-5501) and the Foundation of Transplantation (FDTSFV), Saint Apollinaire, France (CHU-CIC/FT 2010).
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Gualdi, T., Laurent, R., Moutarlier, V. et al. In vitro osteodifferentiation of intact human amniotic membrane is not beneficial in the context of bone repair. Cell Tissue Bank 20, 435–446 (2019). https://doi.org/10.1007/s10561-019-09778-3
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DOI: https://doi.org/10.1007/s10561-019-09778-3