Identification of novel treatment options for osteoarthritis

Osteotreatop

Beschreibung

Osteoarthritis is the most common disabling condition of humans in the western world. Additionally, its incidence is increasing since age and overweight are the most prominent risk factors for initiation and progression of the disease. Damage of articular cartilage frequently leads to osteoarthritis due to the aneural and avascular nature of articular cartilage which impairs regeneration or repair. Therefore, we propose that patients affected by osteoarthritis will benefit from a cell-based transplantation approach. It is the aim of this proposal to use amniotic fluid-derived stem cells as well as adult donor-derived chondrocytes as source material for chondrogenic differentiation. Amniotic fluid stem cells are promising new tools for regenerative medicine since they can be biobanked, proliferate extensively and show multipotent differentiation characteristics. Since mTOR signalling is the main regulator of cell metabolism and differentiation we will assess the role of mTor during in vitro cell differentiation and we will test for conditions to prevent chondrocyte hypertrophy. In parallel we will also analyse patient samples affected by osteoarthritis and correlate mTor activity with progression and stagingof the disease. Finally, successful chondrocyte differentiation will be functionally assessed by transplantation in a human articular cartilage explant system. It is highly anticipated that we will identify novel differentiation protocols that lead to generation of functional chondrocytes for intraarticular transplantation and regeneration of damaged articular joints. Therefore our project has the potential to contribute to the ongoing search for therapies combating this severe social burden and furthermore can be the starting point for new therapeutic interventions.

Kooperationspartner:

Details

Projektzeitraum 05.11.2012 - 30.04.2016
Fördergeber Bundesländer (inkl. deren Stiftungen und Einrichtungen)
Förderprogramm Life Science Call NFB
Department

Department für Gesundheitswissenschaften, Medizin und Forschung

Zentrum für Regenerative Medizin

Projekt­verantwortung (Donau-Universität Krems) Univ.-Prof. Dr. Stefan Nehrer
Projekt­mitarbeit Ass.Prof. Mag. Andrea De Luna, PhD Mag. Dr. Hannes Zwickl

Team

Publikationen

De Luna-Preitschopf, A.; Zwickl, H.; Nehrer, S.; Hengstschläger, M.; Mikula, M. (2017). Rapamycin Maintains the Chondrocytic Phenotype and Interferes with Inflammatory Cytokine Induced Processes. International Journal of Molecular Sciences, 18(7): doi:10.3390/ijms18071494

Preitschopf, A.; Schörghofer, D.; Kinslechner, K.; Schütz, B.; Zwickl, H.; Rosner, M.; Joó, J.G.; Nehrer, S; Hengstschläger, M; Mikula, M. (2016). Rapamycin-Induced Hypoxia Inducible Factor 2A Is Essential for Chondrogenic Differentiation of Amniotic Fluid Stem Cells. Stem Cells Translational Medicine: 580-90

Schörghofer, D.; Kinslechner, K.; Preitschopf, A.; Schütz, B.; Röhrl, C.; Hengstschläger, M.; Stangl, H.; Mikula, M. (2015). The HDL receptor SR-BI is associated with human prostate cancer progression and plays a possible role in establishing androgen independence. Reprod Biol Endocrinol, Vol. 13, No. 88

Üstün, S.; Lassnig, C.; Preitschopf, A.; Mikula, M.; Müller, M.; Hengstschläger, M.; Weichhart, T. (2015). Effects of the mTOR inhibitor everolimus and the PI3K/mTOR inhibitor NVP-BEZ235 in murine acute lung injury models. Transplantation Immunology: 45-50

Preitschopf, A.; Zwickl, H.; Schörghofer, D.; Kinslechner, K.; Schütz, B.; Rosner, M.; Joo, G.J.; Hengstschläger, M.; Nehrer, S.; Mikula, M. (2015). Rapamycin enhances Sox9 Expression during Chondrogenic Differentiation of Amniotic Fluid Stem Cells. Tissue Engineering Part A, September 2015, Volume 21, Supplement 1: 192

Preitschopf, A.; Zwickl, H.; Schörghofer, D.; Kinslechner, K.; Schütz, B.; Rosner, M.; Joó, J.; Hengstschläger, M.; Nehrer, S.; Mikula, M. (2015). Rapamycin enhances SOX9 expression during chondrogenic differentiation of amniotic fluid stem cells. Tissue Engineering Part A: 192-93

Preitschopf, A.; Li, K.; Schörghofer, D.; Kinslechner, K.; Schütz, B.; Thi Thanh Pham, H.; Rosner, M.; Joo, G.; Röhrl, C.; Weichhart, T.; Stangl, H.; Lubec, G.; Hengstschläger, M.; Mikula, M. (2014). mTORC1 is essential for early steps during Schwann cell differentiation of amniotic fluid stem cells and regulates lipogenic gene expression. Plos One

Preitschopf, A.; Busch, J.; Zwickl, H.; Nehrer, S.; Hengstschläger, M.; Mikula, M. (2014). Amniotic Fluid Stem Cells for the Treatment of Articular Cartilage Defects. In: Perinatal Stem Cells: 87-98, Springer Verlag

Preitschopf, A.; Zwickl, H.; Li, K.; Lubec, G.; Joo, G.; Rosner, M.; Hengstschläger, M.; Mikula, M. (2012). Chondrogenic differentiation of amniotic fluid stem cells and their potential for regenerative therapy. Stemm Cell Reviews: 1267-74

Rosner, M.; Mikula, M.; Preitschopf, A.; Feichtinger, M.; Schipany, K.; Hengstschläger, M. (2012). Neurogenic differentiation of amniotic fluid stem cells. Amino Acids: 1591-6

Vorträge

Rapamycin-Induced Hypoxia Inducible Factor 2A Is Essential for Chondrogenic Differentiation of Amniotic Fluid Stem Cells

Osteoarthritis Research Society International World Congress - Amsterdam, Netherlands, 01.04.2016

The role of the mTOR pathway on the chondrogenic differentiation of human amniotic fluid stem cells

Österreichische Gesellschaft für Orthopädie - Vienna,Austria, 30.10.2015

The role of the mTOR pathway on the chondrogenic differentiation of human amniotic fluid stem cells

Tissue Engineering and regenerative Medicine International Society World Kongress - Boston, USA, 11.09.2015

The Role of the mTOR pathway on osteoarthritic chondrocytes

World congress of the International Cartilage Repair Society - Chicago,USA, 08.05.2015

The Role of the mTOR pathway on osteoarthritic chondrocytes

Life Science Meeting - Krems,Austria, 09.04.2015

Chondrogenic differentiation of human amniotic fluid stem cells

Young Scientist Association Symposium-Vienna,Austria, 12.06.2014

Chondrogenic differentiation of amniotic fluid stem cells

World Congress of Regenerative Medicine - Leipzig,Germany, 12.10.2013

Chondrogenic differentiation of amniotic fluid stem cells

Future Investigators of Regenerative Medicine Symposizm-Girona,Spain, 12.09.2013

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