Mercator Fellow

The overall goals of the Mercator Fellowship for the first ExCarBon funding period were:

 

1) To cement the long term partnership between the University of Regensburg and the Oregon Health & Science University, and more specifically between Prof. Angele’s laboratory and Prof. Johnstone’s laboratory. Prof. Johnstone is a former mentor for Prof. Angele and they have had some collaborative efforts over the past 20 years.

 

2) To initiate interactions between Prof. Johnstone and the other members of the consortium and their laboratories that would hopefully lead to extended collaborations. It was envisioned that the interaction begun with the Mercator Fellowship would strengthen ties between the investigators and the institutions. A long-term goal was to facilitate exchange visits of graduate students, fellows and faculty, not only between the Professor Johnstone’s and Angele’s laboratories, but also with the other laboratories of the consortium.

The goals of the first funding period were largely achieved. The following sections describe the successes in detail.

 

 

Visits to Germany

 

It was originally proposed that Prof. Johnstone would spend four months on sabbatical in Regensburg in the first year of the funding period and two 1-week visits in each in the subsequent years. In order to maximize the interactions this was adjusted such that Prof. Johnstone spent a 3-month sabbatical in Regensburg in the first year (9/15/2016 – 1/15/2017), and since then has made eight return visits of 3-6 days each. Two more visits to Regensburg are already planned for 2019 and at least two more will occur in 2020. Activities related to ExCarBon include:

 

          01/12/2017. Mercator Fellow Seminar, University of Regensburg - Speaker.

          09/13-15/2017. EORS, Munich – Organizing Cttee member, Workshop moderator, Presenter.

          03/1-2/2018. ExCarBon meeting, LMU Munich - Participant.

          07/13-14/2018. ExCarbon Summer School, University of Frankfurt – Invited Expert.

          02/7-8/2019. ExCarBon meeting, University Essen-Duisburg - Participant.

          03/28-30/2019. German Society for Matrix Biology meeting/ExcarBon Consortium – Speaker.

 

 

Collaboration with University of Regensburg

 

During Prof. Johnstone‘s three-month sabbatical in Regensburg in the first year of funding, he helped troubleshoot several problems that had arisen with the in vitro chondrogenesis system. This was a crucial assay for both the physioxia studies and cytokine-driven in vitro model of matrix degeneration. He also provided advice on the experimental set-up, reagents needed, and provided methods to be used for the comprehensive analysis of the system once it was operational. In addition, he was present for the initial in vivo studies in rabbits, advising on alternative strategies when the initial ones proved to be unworkable for the desired model. As the work has progressed, productivity has increased with the following output:

 

Presented Abstracts

 

1) Pattappa G, Hofmeister I, Zellner J, Johnstone B, Docheva D, Angele P: Physioxic preconditioning enhances cartilage matrix formation and reduces interleukin-1ß inhibited mesenchymal stem cell chondrogenesis. 25th EORS meeting. Munich, Germany. September 13th – 15th, 2017. Oral

2) Pattappa G, Hofmeister I, Seja J, Zellner J, Johnstone B, Docheva D, Angele P: Development of an in vitro model mimicking early osteoarthritis using mesenchymal stem cells undergoing chondrogenic differentiation. 25th EORS meeting. Munich, Germany. September 13th – 15th, 2017, Oral

3) Hofmeister I, Pattappa G, Seja J, Zellner J, Johnstone B, Docheva D, Angele P: Development of an in vitro model mimicking early osteoarthritis using mesenchymal stem cells undergoing chondrogenic differentiation. DKOU meeting. Berlin, Germany. October 24th – 27th, 2017. Oral

4) Pattappa G, Zellner J, Johnstone B, Docheva D, Angele P: Physioxia enhances and reduces IL-1b inhibited mesenchymal stem cell (MSC) chondrogenesis. eCM meeting, Davos, Switzerland. June 25th-28th, 2018. Oral

5) Pattappa G, Zellner J, Johnstone B, Docheva D, Angele P: Physioxia modulation of IL-1b inhibited chondrogenesis. 26th EORS meeting. Galway, Ireland. September 25th – 28th, 2018. Oral (ON/EORS award winner)

6) Pattappa G, Zellner J, Nerlich M, Johnstone B, Docheva D, Angele P: Mesenchymal stem cell (MSC) chondrogenesis is enhanced and alleviates IL-1b inhibited differentiation under physioxia. DKOU meeting. Berlin, Germany. October 23rd – 26th, 2018. Oral

7) Pattappa G, Franke D, Krueckel J, Johnstone B, Docheva D, Zellner J, Angele P: An in vivo model for evaluating tissue engineering strategies for the treatment of early osteoarthritis. DGMB meeting 2019, Regensburg, Germany. March 28th – 30th.

8) Pattappa G, Krueckel J, Johnstone B, Docheva D, Zellner J, Angele P: Physioxia preconditioned mesenchymal stem cells demonstrate improved cartilage regeneration for the treatment of early osteoarthritic defects. DGMB meeting, Regensburg, Germany. March 28th – 30th, 2019.

9) Pattappa G, Franke D, Krueckel J, Koch M, Weber J, Bohrer A, Lang S, Johnstone B, Docheva D, Zellner J, Angele P: An in vivo defect model for testing cell-based tissue engineering strategies for early osteoarthritis. International Combined Orthopaedic Research Societies (ICORS) Meeting, Montreal, Canada. June 19th – 22nd, 2019. Oral

10) Pattappa G, Schewior R, Hofmeister I, Seja J, Zellner J, Johnstone B, Docheva D, Angele P: Physioxia improves cartilage matrix gene expression and GAG content in IL-1b inhibited chondrogenesis. International Combined Orthopaedic Research Societies (ICORS) Meeting, Montreal, Canada. June 19th – 22nd, 2019. Poster

11) Franke D, Pattappa G, Krueckel J, Koch M, Weber J, Bohrer A, Lang S, Johnstone B, Docheva D, Zellner J, Angele P: An in vivo defect model for testing cell-based tissue engineering strategies for early osteoarthritis. DKOU meeting. Berlin, Germany. October 22nd– 25th, 2019. Oral

12) Franke D, Pattappa G,, Krueckel J, Koch M, Weber J, Bohrer A, Lang S, Johnstone B, Docheva D, Zellner J, Angele P: Physioxic preconditioned mesenchymal stem cells shows improved cartilage repair for treatment of early osteoarthritis in an in vivo animal model. DKOU meeting. Berlin, Germany. October 22nd – 25th, 2019. Poster

 

Published Manuscripts

 

1) Pattappa G, Zellner J, Johnstone B, Docheva D, Angele P. Cells under pressure – the relationship between hydrostatic pressure and mesenchymal stem cell chondrogenesis. Eur Cell Mater. 2019;37:360-381. doi: 10.22203/eCM.v037a22.

2) Pattappa G, Johnstone B, Zellner J, Docheva D, Angele P. The importance of physioxia in mesenchymal stem cell chondrogenesis and the mechanisms controlling its responses. Int J Mol Sci. 2019;20(3). pii: E484. doi: 10.3390/ijms20030484.

3) Pattappa G, Schewior R, Hofmeister I, Seja J, Zellner J, Johnstone B, Docheva D, Angele P. Physioxia has a beneficial effect on cartilage matrix production in interleukin-1 beta inhibited Mesenchymal Stem Cell chondrogenesis. Cells [in revision].

 

 

Collaborative Activities with the Other ExCarBon Groups

 

Prof. Johnstone participated in almost all ExCarbon activities. He provided expert feedback to all projects at the research update meetings, and corresponded separately with various project leaders to develop collaborations outside of the Angele (SP7) project interactions described below:

 

          SP2 (Vortkamp) - An RNA-Seq project not directly related to ExCarBon.         

          SP3 (Richter) - The miRNA project that resulted in a publication (see below).

          SP4 (Grässel) - Normal human chondrocytes and articular cartilage as healthy controls for the project.

          SP8 (Jenei-Lanzi) - Studies of ß2-adrenergic signaling in cartilage progenitor cells.

  

Published Manuscripts

 

Hecht N, Johnstone B, Angele P, Walker T, Richter W. Mechanosensitive MiRs regulated by anabolic and catabolic loading of human cartilage. Osteoarthritis Cartilage. 2019. pii: S1063-4584(19)30950-1. doi: 10.1016/j.joca.2019.04.010. [Epub ahead of print]

 

 

One of the objectives of DFG grants like ExCarBon is to draw researchers together, and lead to the expansion of science to produce other fundable science and ultimately contribute to the translation of new therapies. ExCarBon has succeeded in expanding the collaborative efforts between al the groups involved.

 

 

Exchange Visits

 

The first exchange visit will occur in summer, 2019. Jonas Krueckel, medical student, University of Regensburg, will spend three months in the Department of Orthopaedics and Rehabilitation at OHSU. He has been awarded a grant from the German Society for Orthopaedics and Orthopaedic Surgery to cover some costs of his visit. The visit combines research in the laboratory of Prof. Johnstone with a rotation through the clinical services of the department. Discussions have begun with other consortium members for similar exchange visits.

 

The Society for Arthroscopy and Joint Surgery, Germany (AGA) in collaboration with DJO/Aircast, will begin sponsoring an 18-month fellowship for young physicians to work in Prof. Johnstone’s laboratory. This will begin in 2020 and recur at 2-year intervals. This new fellowship recognizes the long-term involvement of Prof. Johnstone with German orthopaedic researchers, and in particular his collaborative research with Prof. Angele (SP7) that was augmented by the ExCarBon Mercator Fellowship.

The consortium has asked Prof. Johnstone to continue as the Mercator Fellow for the renewal application.

 

 

Collaborative Science With AG Angele (SP7)

 

The SP7 continuation project remains focused in the area of research that Prof. Johnstone works in. Having access to healthy human articular cartilage with viable cells, he will provide tissues and cells as needed for the new studies proposed. He will again spend extended periods at the University of Regensburg to contribute more fully to experimental design, interpretation, troubleshooting et cetera.

 

 

Contributions to the Other ExCarBon Projects

 

During his sabbatical period in Regensburg, Prof. Johnstone was also present for the ongoing presentations of work for the other Regensburg-based project of Prof. Grässel (SP4). He contributed to the critical evaluation of the project and this led to the collaborative project listed above (1.3), which is ongoing. As also noted in 1.3, the interaction of Prof. Johnstone with all of the project leaders and their teams, has led to other collaborations that are also all still ongoing. Prof. Johnstone will spend time at the other project sites as appropriate to further these studies.