iPS cell generation from jaw periosteum: is the resulting osteogenic capacity more efficient?
Final Report Abstract
New and effective therapies are urgently needed in the field of oral and maxillofacial surgery to enable regeneration of in particular large bone defects. Tissue engineering strategies represent the most promising therapeutic option. The unique specialization of jaw periosteal cells (JPCs), withstanding high mechanical load during mastication, makes them to attractive candidates for cell-based therapies for oral and maxillofacial surgeries. In the first funding period of our joint project, we generated for the first time induced pluripotent stem (iPS) cells from jaw periosteal cells and successfully published this work. We established a completely xeno-free protocol and used a selfreplicating RNA construct in order to perform a footprint-free cell reprogramming. In the next step, we generated induced mesenchymal stromal cells (iMSCs) from these iPS cells, which in turn showed strong mineralization potential in 2D culture. In view of future clinical application, we move forward to develop iMSC-seeded 3D constructs and test cell functions (particularly the differentiation potential) and biocompatibility of constructs in vitro and in vivo by using an immunodeficient mouse model. By the realization of this project, we open up a new stem cell source for bone tissue engineering and establish a clinically applicable approach for iPS cell-based therapies.
Publications
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Efficient reduction of synthetic mRNA induced immune activation by simultaneous delivery of B18R encoding mRNA. Journal of Biological Engineering, 13(1).
Michel, Tatjana; Golombek, Sonia; Steinle, Heidrun; Hann, Ludmilla; Velic, Ana; Macek, Boris; Krajewski, Stefanie; Schlensak, Christian; Wendel, Hans Peter & Avci-Adali, Meltem
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Generation of iPSCs by Nonintegrative RNA-Based Reprogramming Techniques: Benefits of Self-Replicating RNA versus Synthetic mRNA. Stem Cells International, 2019, 1-16.
Steinle, Heidrun; Weber, Marbod; Behring, Andreas; Mau-Holzmann, Ulrike; Schlensak, Christian; Wendel, Hans Peter & Avci-Adali, Meltem
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Generation of iPSCs from Jaw Periosteal Cells Using Self-Replicating RNA. International Journal of Molecular Sciences, 20(7), 1648.
Umrath, Felix; Steinle, Heidrun; Weber, Marbod; Wendel, Hans-Peter; Reinert, Siegmar; Alexander, Dorothea & Avci-Adali, Meltem
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Generierung von induzierten pluripotenten Stammzellen aus Kieferperiostzellen. 2019 Kongress der Deutschen Gesellschaft für Mund-, Kiefer- und Gesichtschirurgie
Umrath F., Steinle H., Reinert S., Avci-Adali M. & Alexander D.
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Reprogramming of Urine-Derived Renal Epithelial Cells into iPSCs Using srRNA and Consecutive Differentiation into Beating Cardiomyocytes. Molecular Therapy - Nucleic Acids, 17, 907-921.
Steinle, Heidrun; Weber, Marbod; Behring, Andreas; Mau-Holzmann, Ulrike; von Ohle, Christiane; Popov, Aron-Frederik; Schlensak, Christian; Wendel, Hans Peter & Avci-Adali, Meltem
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Structural and biochemical analysis of extracellular matrix formed by jaw periosteal cells. 2019 Tissue Engineering and Regenerative Medicine International Society (TERMIS)
Alexander D., Danalache M., Kliesch S. M., Munz M. & Reinert S.
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Improving the Footprint-Free iPSC Generation by Nonintegrative Self-Replicating RNA-Based Reprogramming. The Thoracic and Cardiovascular Surgeon. Georg Thieme Verlag KG.
Avci-Adali, M.; Steinle, H.; Weber, M.; Behring, A.; Mau-Holzmann, U.; Wendel, H. P. & Schlensak, C.
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iPSC-Derived MSCs Versus Originating Jaw Periosteal Cells: Comparison of Resulting Phenotype and Stem Cell Potential. International Journal of Molecular Sciences, 21(2), 587.
Umrath, Felix; Weber, Marbod; Reinert, Siegmar; Wendel, Hans-Peter; Avci-Adali, Meltem & Alexander, Dorothea
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Pluripotency Evaluation of Newly Generated iPSC Lines using Chorioallantoic Membrane Assay. The Thoracic and Cardiovascular Surgeon. Georg Thieme Verlag KG.
Weber, M.; Baur, J.; Steinle, H.; Wendel, H. P.; Avci-Adali, M. & Schlensak, C.
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Ramanspektroskopische Analysen von dreidimensionalen Zell-besiedelten β-Trikalziumphosphat Konstrukten. 2020 Kongress der Deutschen Gesellschaft für Mund-, Kiefer- und Gesichtschirurgie
Alexander D., Kliesch S. M., Danalache M. & Reinert S.
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Untersuchungen zur Hämokompatibilität von Zell-besiedelten β-Trikalziumphosphat Scaffolds. 2022 Kongress der Deutschen Gesellschaft für Mund-, Kiefer- und Gesichtschirurgie
Weber M., Schmitt L.F., Umrath F., Reinert S., Avci-Adali M. & Alexander D.
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An alternative in vivo model to evaluate pluripotency of patient-specific iPSCs. ALTEX, 2021.
Weber, Josefin
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Analyses of periosteal-seeded β-tricalcium phosphate constructs by Raman spectroscopy. 2021 (digital) Tissue Engineering and Regenerative Medicine International Society (TERMIS)
Alexander D., Umrath F., Kliesch S. M., Geis-Gerstorfer J. & Reinert S.
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Influence of Human Jaw Periosteal Cells Seeded β-Tricalcium Phosphate Scaffolds on Blood Coagulation. International Journal of Molecular Sciences, 22(18), 9942.
Weber, Marbod; Umrath, Felix; Steinle, Heidrun; Schmitt, Lukas-Frank; Yu, Lin Tzu; Schlensak, Christian; Wendel, Hans-Peter; Reinert, Siegmar; Alexander, Dorothea & Avci-Adali, Meltem
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Ramanspektroskopische Analysen von dreidimensionalen Zell-besiedelten β-Trikalziumphosphat Konstrukten. 2021 Kongress der Deutschen Gesellschaft für Mund-, Kiefer- und Gesichtschirurgie
Alexander D., Umrath F., Kliesch S.M., Schmitt L.F., Geis-Gerstorfer J. & Reinert S.
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Footprint-free generation of induced pluripotent cells and their application in regenerative medicine, 2022 Bone and Joint Congress "Bone and Joint Regeneration“ Kyrenia, Cyprus (30.09.2022)
M. Avci-Adali
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Pre-Conditioning with IFN-γ and Hypoxia Enhances the Angiogenic Potential of iPSC-Derived MSC Secretome. Cells, 11(6), 988.
Wang, Suya; Umrath, Felix; Cen, Wanjing; Salgado, António José; Reinert, Siegmar & Alexander, Dorothea
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Mechanical and Functional Improvement of β-TCP Scaffolds for Use in Bone Tissue Engineering. Journal of Functional Biomaterials, 14(8), 427.
Umrath, Felix; Schmitt, Lukas-Frank; Kliesch, Sophie-Maria; Schille, Christine; Geis-Gerstorfer, Jürgen; Gurewitsch, Elina; Bahrini, Kathleen; Peters, Fabian; Reinert, Siegmar & Alexander, Dorothea
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Synthetic mRNA-based approaches for tissue regeneration – Application potential for the treatment of osteoarthritis, COST (European Cooperation in Science & Technology)-Articular Cartilage Engineering Training School, Istanbul, Turkey (01.12.2023- 02.12.2023)
M. Avci-Adali
