Academic Center for Stem Cells & Organoids in personalized and REgenerative medicine (SCORE)

ACE SCORE aims to promote interactions and collaborations between fundamental and translational research efforts in multiple disciplines relating to stem cells and organoids, to accelerate innovation and bring regenerative and personalized medicine approaches closer to the patient.

Academic Center of Excellence

Research Activities

The research groups participating in ACE SCORE focus on understanding cellular and molecular mechanisms controlling stem cell potency, fate and function and their role in disease, development and regeneration. SCORE members further work on translating these insights into regenerative and personalized medicine applications. Our main research efforts focus on:

  • Understanding cellular and molecular mechanisms controlling stem cell potency, fate and function and their role in development, disease, oncology and regeneration.
  • Modelling normal and pathological development, complex disease, tumor progression and therapy responsiveness using pluripotent and adult stem cells and organoids, to study disease pathogenesis and performing diagnostics or drug screening for personalized medicine.
  • Using stem cells and organoids for tissue repair, gene therapy and immunomodulation.

Type of

Collaborations

Research consortia with ACE SCORE contributions include the HOVON Leukemia Working Group and the EBMT Acute Leukemia Working Party. Within the human disease models technology (hDMT) consortium iPS differentiation and organoid technology is united with TU Delft, Eindhoven and Twente in close collaboration with the Harvard affiliated Wyss institute.

With the appointment of the Querido Chair to prof. Zandstra (Toronto) we have made connections with the Center for Commercialization of Regenerative Medicine (CCRM) in Toronto, with the aim to improve links with technology as well as commercialization.

In the context of the Medical Delta, ACE SCORE coordinates the development of a regenerative medicine proposal. We believe the time has come to embed the theme regenerative medicine into the Medical Delta.

ACE SCORE is actively investigating participation in the RegMedXB Dutch/Belgian consortium to cooperatively tackle ambitious challenges in regenerative medicine.

Educational

Contributions

Education on stem cells and tissue regeneration is well developed during bachelor and master education at Erasmus. The group members teach in Bachelor of Medicine, Nanobiology, Clinical Technology, Master of Medicine as well as the research master Molecular Medicine. The Bachelor of Medicine minor 'Biomedical Research in Practice', in which multiple ACE SCORE members contribute to a module about stem cells and organoids, was awarded the MORE onderwijsprijs for best minor 2017/2018.

ACE SCORE has developed a PhD course on Stem cells, Organoids and Regenerative Medicine. This course took place from 27 to 30 November 2018 and featured lecturers from ErasmusMC and LUMC in addition to multiple networking opportunities. The limit of 40 registrations was exceeded, indicating the need for a course about this topic. After an initial catch-up period in which the course will run yearly, we anticipate a bi-yearly frequency.

Patient

Care Activities

The road from lab to patient care is long and slow. We identified several areas of research in ACE SCORE which we expect are most likely to impact patient care within the next few years:

  • Currently, the Department of Haematology is preparing a phase I/II clinical trial that will evaluate the feasibility and efficacy of expanded cord blood stem cells in patients with high-risk leukemia's, using the ATMP (advanced therapy medicinal products) facility. Also, several phase 3 registration trials in acute myeloid leukemia are about to start.
  • Epithelial organoid models of cancer and other diseases of epithelial organs (e.g. liver, kidney, intestine) such as cholangiocarcinoma, cystic fibrosis and viral infections are used for drug screening and are likely to impact diagnosis and selection of treatment options in the near future. Indeed, for cystic fibrosis this is already happening.
  • The Department of Orthopaedics is involved in an industry coordinated trial on the use of mesenchymal stem cells for osteonecrosis treatment.
  • The practice of liver, kidney and lung transplantation is likely to benefit within the next few years from advances using machine perfusion to condition and improve transplantable organs. Repair of endothelium in kidneys for transplantation using machine perfusion may enter clinical trials within the next 2 years. A slightly longer time line is expected for work in introducing immune-modulating cells into liver and lung during machine perfusion prior to transplantation to improve transplantation results.
  • A similar time frame concerns efforts to dampen inflammation and/or promote regeneration by introductions of mesenchymal stem cells in cases of osteoarthritis, large bone defects, liver failure and to prevent graft rejection after kidney transplantation.
  • ACE members are actively involved in the 2018 Foundation NFU Expertise Center for Bone Marrow Failure and Leukemia Predisposition (Collaboration Erasmus MC and Leiden University MC, Director M. Raaijmakers). work groups. A European work group under auspices of the European Society of Hematology addressing genetic predisposition of myeloid malignancies is being created.

These advances indicate that knowledge and expertise from the ACE slowly infiltrate into clinical practice.

Societal Relevance to Research, Education and Patient Care

SCORE aims to promote interactions that lead to the development of new therapies and diagnostics. Society has indicated this to be important. Several members play active roles in explaining new developments and applications in stem cell research to society and decision making parties, see also our non-scientific publications. Score members are involved in national committees such as ZONMW Translational Adult Stem Cells, ZONMW Programma Translationeel Onderzoek and the kennisagenda voor NWA route Regenerative Medicine, and in advisory boards, e.g. the Dutch Horizon-committee for expensive drugs of the Dutch Ministry of Health.

SCORE members are actively involved as board members in (inter)national research networks and societies focussed on regenerative medicine such as Netherlands Organs on a Chip Initiative (Gravity), Netherlands Society for Tissue engineering and Biomaterials (NVMB), Tissue Engineering and Regenerative Medicine International Society (TERMIS), European Society for Blood and Marrow Transplantation (EBMT), the Dutch-Belgian cooperative study group for patients with hematological malignancies (HOVON), the Board and Steering Committee of the HOVON Leukemia Trial Group, the Dutch Hepatocellular & Cholangiocarcinoma Group (DHCG) Biobanking group, the European Network for Studies on Cholangiocarcinoma (ENSCCA), and the Scientific Counsel of the Dutch Cancer Society.

Our members also serve in advisory boards such as he Dutch Horizon-committee for expensive drugs of the Dutch Ministry of Health and the Werkgroep Stamcel Laboratoria Nederland (WSN), and contribute to clinical guidelines for e.g. myelodysplastic syndromes, acure myeloid leukemia and aplastic anemia. They further contribute to policy documents and instruments: 'The European Hematology Association Roadmap for European Hematology Research: a consensus document'. Haematologica February 2016, 101: 115-208.

Viability of Research, Education and Patient Care

ACE SCORE considers its core mission the active promotion of interactions between ACE SCORE members and with members of relevant other ACEs, e.g. ACE Bone and Joint and ACE Systems Biomedicine, with the aim to inspire new collaborations and new research, better education in the fields of stem cells and regenerative medicine, and regenerative medicine innovations in patient care.

We pursue this mission by enabling a variety of interaction formats. Yearly ACE days combine short, almost pitch-like presentations with informal networking formats. For example, at our ACE DAY on 31 October 2017 in the Science Tower Rotterdam, we introduced our ACE FORCE concept, in which presubmitted research questions were discussed by varying groups of ACE members to find creative solutions outside the usual circle of the submitting researcher. Focus groups, e.g. on the topics of iPS cells, mesenchymal stem cells, and the ROEM group (Rotterdam Organoid Experience Meeting) on organoids, meet more frequently to exchange practical information and inform rapidly evolving insights. In addition, ACE SCORE has over the past year (co-)organized 7 seminars and 2 symposia.

We actively invite promising (junior) researchers to attend these meetings and participate in the ACE activities, to ensure the inflow of new views and complementary research interests. The ACE has thereby gained 5 additional PI members over the past year.

In addition, the ACE SCORE coordinator team actively pursues opportunities for participation in (inter)national networks, e.g. RegMedXB, and coordinates collaborative grant proposals, e.g. in the context of the Medical Delta, NWA, and European Union (such as a Flagship proposal).

There are many links that connect individual groups in our ACE. These are fruitful as is already demonstrated by > 35 joint papers and >17 joint grants over the past 5 years. Since ACE SCORE is only in existence for 2 years it is not yet possible to evaluate the impact of the ACE on publications and grants.

The impact of the ACE on education and patient care is described in the respective sections.

Key and relevant publications of the last five years

  • R.R. Ruela-de-Sousa, E. Hoekstra, A.M. Hoogland, K.C. Souza Queiroz, M.P. Peppelenbosch, A.P. Stubbs, K. Pilazzaro-Rocha, G.J. van Leenders, G. Jenster, H. Aoyama, C.V. Ferreira, G.M. Fuhler. Low-molecular weight protein tyrosine phosphatase predicts prostate cancer outcome by increasing the metastatic potential. Eur Urol. 2015; jul6. Pii:S0302-2838(15)00543-6. Q1 IF 16.265
  • Barakat TS, Halbritter F, Zhang M, Rendeiro AF, Perenthaler E, Bock C, Chambers I.Cell Stem Cell. 2018 Aug 2;23(2):276-288.e8. doi: 10.1016/j.stem.2018.06.014. Epub 2018 Jul 19. Functional dissection of the enhancer repertoire in Human Embryonic Stem Cells (IF 23.4)
  • Wanlu Cao, Kan Chen, Michiel Bolkestein, Yuebang Yin, Monique M. A. Verstegen, Marcel. J. C. Bijvelds, Wenshi Wang, Nesrin Tuysuz, Derk ten Berge, Dave Sprengers, Herold J. Metselaar, Luc J. W. van der Laan, Jaap Kwekkeboom, Ron Smits, Maikel P. Peppelenbosch and Qiuwei Pan* Dynamics of Proliferative and Quiescent Stem Cells in Liver Homeostasis and Injury. Gastroenterology. 2017 Oct;153(4):1133-1147. (IF: 20.8; Q1)
  • Nesrin Tüysüz, Louis van Bloois, Stieneke van den Brink, Harry Begthel, Monique M.A. Verstegen, Luis J. Cruz, Lijian Hui, Luc J.W. van der Laan, Jeroen de Jonge, Robert Vries, Eric Braakman, Enrico Mastrobattista, Jan J. Cornelissen, Hans Clevers, Derk ten Berge (2017) Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells. NATURE COMMUNICATIONS 8, 14578. Top 10%. 8 citations.
  • Dekkers JF, Wiegerinck CL, De Jonge HR, Bronsveld I, Janssens HM, De Winter-De Groot KM, Bijvelds MJC, Nieuwenhuis EES, Van den Brink S, Clevers H, Van der Ent CK, Middendorp S, Beekman JM. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nature Med 19: 939-945, 2013. Ranking of journal: number 1 in field: Medicine (Research) Number of citations: 253
  • Aparicio-Domingo P, Romera-Hernandez M, Karrich JJ, Cornelissen F, Papazian N, Lindenbergh-Kortleve DJ, Butler JA, Boon L, Coles MC, Samsom JN, Cupedo T.Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage.J Exp Med. 2015 Oct 19;212(11):1783-91. Impact factor: 10.79. Top 5% of field (Immunology) Citations: 40
  • Stock K, Falcão Estrada M, Vidic S, Gjerde K, Rudisch A, Espírito Santo V, Barbier M, Blom S, Arundkar S, Selvam I, Osswald A, Stein Y, Gruenewald S, Brito C, van Weerden WM, Rotter V, Boghaert E, Oren M, Sommergruber W, Chong Y, de Hoogt R, and Graeser R. Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery. Sci Rep 6 (2016): 28951. IF: 4.2. Ranking in field: 12/64 (multidisciplinary sciences) Citation: 25
  • Engelen E., Brandsma J.H., Moen M.J., Signorile L., Dekkers D.H., Demmers J., Kockx C.E.M., Ozgur Z., van IJcken W.F.J., van den Berg D.L.C., Poot R.A. (2015) Proteins that bind regulatory regions identified by histone modification chromatin immunoprecipitations and mass spectrometry. Nature Commun. 2015; 6: 7155. IF 12.4, Ranked 3rd in general science journals, 21 citations.
  • Narcisi R, Cleary MA, Brama PA, Hoogduijn MJ, Tüysüz N, Ten Berge D, van Osch GJ. Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation. Stem Cell Reports. 2015 Mar 10;4(3):459-72. 34 citations in web of science. Journal ranking: 3/24
  • Schewe M, Franken PF, Sacchetti A, Schmitt M, Joosten R, Böttcher R, van Royen ME, Jeammet L, Payré C, Scott PM, Webb NR, Gelb M, Cormier RT, Lambeau G, Fodde R. Secreted Phospholipases A2 Are Intestinal Stem Cell Niche Factors with Distinct Roles in Homeostasis, Inflammation, and Cancer. Cell Stem Cell. 2016 Jun 7. pii: S1934-5909(16)30107-2.
  • Zambetti NA, Ping Z, Chen S, Kenswil KJG, Mylona MA, Sanders MA, Hoogenboezem RM, Bindels EMJ, Adisty MN, Van Strien PMH, van der Leije CS, Westers TM, Cremers EMP, Milanese C, Mastroberardino PG, van Leeuwen JPTM, van der Eerden BCJ, Touw IP, Kuijpers TW, Kanaar R, van de Loosdrecht AA, Vogl T, Raaijmakers MHGP. Cell Stem Cell. 2016 Nov 3;19(5):613-627. doi: 10.1016/j.stem.2016.08.021.

PhD theses of the last five years

  • Romera-Hernandez, M Patching up the crypt: Innate immune cells orchestrate intestinal regeneration 2018
  • Pleumeekers, MM Face-It: cell-based therapy for the reconstruction of cartilage defects in the head and neck area 2018
  • Schewe, M Paneth cells: tales of a gutsy cell 2018
  • Witte, SFH Probing the Immunomodulatory potential of Mesenchymal Stem Cells 2018
  • Cao, W Dynamics of stem cells in liver homeostasis, injury and carcinogenesis 2018
  • Versluis, J Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplantation, Post-remission treatment, Personalized medicine 2017
  • Magaraki, A Epigenetic regulation in rodent primordial germ cells and preimplantation embryos 2017
  • Yin, Y Modeling infection and antiviral therapy of enteric viruses using primary intestinal organoids 2017
  • Duinhouwer, LE Improving Umbilical Cord Blood Stem Cell Engraftment by Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells 2016
  • Cleary, M Enhancing Chondrogenesis of Mesenchymal Stem Cells: taking inspiration from joint development 2016
  • Hoon de, B Mechanisms and clinical implications of human X chromosome inactivation 2016
  • Chatalic, K Towards personalised treatment for prostate cancer: GRPR- and PSMA-targeted theranostic agents for imaging and therapy of prostate cancer 2016
  • Tüysüz, N Effects of Wnt signaling proteins on maintenance and expansion of adult stem cells 2015
  • Roth, S Silent waters run deep: Quiescent stem cells in homeostasis and cancer 2013
  • Atlasi, Y Wnt signaling in stem cells and cancer 2013

Non-scientific publications related to the ACE

  • Quanta Magazine, an international popular science magazine published by the Simons Foundation and syndicated throughout the world, e.g. by Wired, The Atlantic, Scientific American and Spektrum der Wissenschaft, published an article (29/8/2018) featuring an interview with Riccardo Fodde and one of his recent papers about regeneration. https://www.quantamagazine.org/in-paligenosis-adult-cells-turn-fetal-to-heal-wounds-20180829/
  • Interview with Roberto Narcisi for the newsletter of the International Cartilage Regeneratoin & Joint Preservation Society ICRS: https://cartilage.org/newsletters/18414/ page 42.
  • Movie featuring a lecture by Roberto Narcisi as part of a high school program financed by the Italian minister of education where experts in different fields share their work and life experiences to inspire high school students in their academic choices.
  • Television presentation on SBS-Hart van Nederland on Monday 6 April 2015. Interview with Hugo de Jonge about cystic fibrosis research.
  • Volkskrant, Wetenschaps bijlage 25 april 2015 p. 12-17: “Voeding als Medicijn”, featuring Hugo de Jonge.
  • Public lecture by Danny Huylebroeck at the Medical Dispute 'Vesalius', Rotterdam 2018.
  • Euronews short movie on personalized cartilage repair using stem cells: http://www.euronews.com/2018/03/12/finding-new-cures-for-osteoarthritis
  • NRC, wetenschapsbijlage 9 maart 2018: “Straks groeit je donornier misschien in een varken”, featuring Joost Gribnau.
  • NOS.nl 25 januari 2018: “China trots op klonen aap, westerse wetenschappers bezorgd”, featuring Joost Gribnau.
  • Medisch Contact, 20 januari 2016: “Dure geneesmiddelen: samenwerking loont”, met Jan Cornelissen.
  • The work of Marc Raaijmakers featured online in many Dutch and International newspapers and scientific magazines including: Nu.nl, De Telegraaf, Avro/Tros, ZONMW-Mediator (http://mediator.zonmw.nl/mediator-21-januari-2017/we-kunnen-leukemie-nu-beter-voorspellen), Nemokennislink.nl.
Last updated: 345 days ago.