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Publication

Dr Yolande Ramos and international colleagues publish review in Osteoarthritis and Cartilage

Congratulations to Leiden University Medical Center‘s Yolande F.M. Ramos and international colleagues Sarah J. Rice, Shabana Amanda Ali, Chiara Pastrello, Igor Jurisica, Muhammad Farooq Rai, Kelsey H. Collins, Annemarie Lang, Tristan Maerz, Jeroen Geurts, Cristina Ruiz-Romero, Ronald K. June, C. Thomas Appleton, Jason S. Rockel, Mohit Kapoor! Their review article titled: Evolution and advancements in genomics and epigenomics in OA research: How far we have come was published on February 28th, 2024 in the journal Osteoarthritis and Cartilage. 

DOI: https://doi.org/10.1016/j.joca.2024.02.656

 

Dr Yolande Ramos and international colleagues publish review in Osteoarthritis and Cartilage2024-03-27T13:24:20+00:00

Joint AutoCRAT paper in Processes from Fraunhofer IPT and U of Galway

Congratulations to AutoCRAT researchers at Fraunhofer IPT and the University of Galway for their recent publications in the journal Processes (ISSN 2227-9717). It will be part of a special issue, “Application of Deep Learning in Pharmaceutical Manufacturing”

The article is titled: Automated Production at Scale of Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells, Chondrocytes and Extracellular Vehicles: Towards Real-Time Release. Author/researchers Laura Herbst, Ferdinand Groten, Mary Murphy, Georgina Shaw, Bastian Nießing, and Robert H. Schmitt published the paper on October 10th, 2023. Download the PDF here.

Citation:

Herbst L, Groten F, Murphy M, Shaw G, Nießing B, Schmitt RH. Automated Production at Scale of Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells, Chondrocytes and Extracellular Vehicles: Towards Real-Time Release. Processes. 2023; 11(10):2938. DOI: https://doi.org/10.3390/pr11102938

Abstract: 

Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) are amenable for use in a clinical setting for the treatment of osteoarthritis (OA), which remains one of the major illnesses worldwide. Aside from iPSC-derived iMSCs, chondrocytes (iCHO) and extracellular vesicles (EV) are also promising candidates for the treatment of OA. Manufacturing and quality control of iPSC-derived therapies is mainly manual and thus highly time-consuming and susceptible to human error. A major challenge in translating iPSC-based treatments more widely is the lack of sufficiently scaled production technologies from seeding to fill-and-finish. Formerly, the Autostem platform was developed for the expansion of tissue-derived MSCs at scale in stirred tank bioreactors and subsequent fill-and-finish. Additionally, the StemCellDiscovery platform was developed to handle plate-based cultivation of adherent cells including their microscopic analysis. By combining the existing automation technology of both platforms, all required procedures can be integrated into the AutoCRAT system, designed to handle iPSC expansion, differentiation to iMSCs and iCHOs, pilot scale expansion, and formulation of iMSCs as well as extracellular vesicles and their purification. Furthermore, the platform is equipped with several in-line and at-line assays to determine product quality, purity, and safety. This paper highlights the need for adaptable and modular automation concepts. It also stresses the importance of ensuring the safety of generated therapies by incorporating automated release testing and cleaning solutions in automated systems. The adapted platform concepts presented here will help translate these technologies for clinical production at the necessary scale.
Joint AutoCRAT paper in Processes from Fraunhofer IPT and U of Galway2023-10-19T08:55:39+00:00

Collaborative AutoCRAT publication in Theranostics

Congratulations to the team of AutoCRAT researchers/authors at the University of Genoa and the University of Galway and their collaborators for the open-access publication of “Xeno-free cultured mesenchymal stromal cells release extracellular vesicles with a “therapeutic” miRNA cargo ameliorating cartilage inflammation in vitro” in the journal Theranostics on March 5th, 2023.

 

Citation:  Palamà, M.E.F., Coco, S., Shaw, G.M., Reverberi, D., Ghelardoni, M., Ostano, P., Chiorino, G., Sercia, L., Persano, L., Gagliani, M.C., Cortese, K., Pisignano, D., Murphy, J.M., Gentili, C. (2023). Xeno-free cultured mesenchymal stromal cells release extracellular vesicles with a “therapeutic” miRNA cargo ameliorating cartilage inflammation in vitro. Theranostics, 13(5), 1470-1489. https://doi.org/10.7150/thno.77597.

Download the PDF here.

Collaborative AutoCRAT publication in Theranostics2023-03-13T12:28:59+00:00

Congratulations to our partners at Fraunhofer IPT for the latest AutoCRAT publication in the journal Processes

“Additively Manufactured Robot Gripper Blades for Automated Cell Production Processes”, a journal article prepared by our partners at Fraunhofer Institute for Production Technology (IPT) was published in the MDPI’s Processes on October 14th, 2022.

Congratulations to researcher-authors Ferdinand Biermann, Stefan Gräfe, Thomas Bergs and Robert H. Schmitt!

Citation: Biermann, F.; Gräfe, S.; Bergs, T.; Schmitt, R.H. Additively Manufactured Robot Gripper Blades for Automated Cell Production Processes. Processes 2022, 10, 2080. https://doi.org/10.3390/pr10102080

Download the open-access paper here.

Congratulations to our partners at Fraunhofer IPT for the latest AutoCRAT publication in the journal Processes2022-10-17T15:14:29+00:00

AutoCRAT collaborative publication in Stem Cell Research & Therapy

Congratulations to authors Yolande F. M. Ramos,  Tobias Tertel,  Georgina Shaw,  Simon Staubach, Rodrigo Coutinho de Almeida, Eka Suchiman, Thomas B. Kuipers, Hailiang Mei, Frank Barry, Mary Murphy, Bernd Giebel and Ingrid Meulenbelt! The inter-institutional team of researchers from the LUMC, NUI Galway and Universitaetklinikum Hospital Essen have published the study entitled: Characterizing the secretome of licensed hiPSC-derived MSCs in the journal Stem Cell Research & Therapy on September 2nd, 2022.

Read the open access paper here.

Citation for this paper: Ramos, Y.F.M., Tertel, T., Shaw, G. et al. Characterizing the secretome of licensed hiPSC-derived MSCs. Stem Cell Res Ther 13, 434 (2022). https://doi.org/10.1186/s13287-022-03117-2

 

 

AutoCRAT collaborative publication in Stem Cell Research & Therapy2022-09-08T12:09:37+00:00

Publication news! AutoCTRAT research by UGOT published in Cell Regeneration

Congratulations to researchers and authors at the University of Gothenburg and Cline Scientific, H. Evenbratt, L. Andreasson, V. Bicknell, M. Brittberg, R. Mobini and S. Simonsson. Their study entitled: Insights into the present and future of cartilage regeneration and joint repair appears in the journal Cell Regeneration, (Cell Regen 11, 3 (2022). https://doi.org/10.1186/s13619-021-00104-5) today, February 2nd, 2022.

Download the open-access PDF here.

Publication news! AutoCTRAT research by UGOT published in Cell Regeneration2022-02-02T15:34:42+00:00

New AutoCRAT publication from AutoCRAT team at the Universita di Genova

Congratulations to the AutoCRAT research team at the Universita di Genova for their recent publication in STEM CELLS Translational Medicine. Cansu Gorgun, Maria Elisabetta Palamà, Daniele Reverberi, Maria Cristina Gagliani, Katia Cortese, Roberta Tasso, and Chiara Gentili published “Role of from adipose tissue- and bone marrow-mesenchymal stromal cells in endothelial proliferation and chondrogenesis” in STEM CELLS Translational Medicine.

In addition, their image was chosen for the December 2021 issue, Volume 10, Issue 12. Well done!

The DOI for this paper is https://doi.org/10.1002/sctm.21-0107  You can download the PDF of the open-access paper here.

New AutoCRAT publication from AutoCRAT team at the Universita di Genova2021-12-09T16:13:17+00:00

UNIGE announces third AutoCRAT-acknowledged publication!

The team of researchers Cansu Gorgun, Maria Elisabetta Federica Palamà, Daniele Reverberi, Maria Cristina Gagliani, Katia Cortese, Roberta Tasso, and Chiara Gentili of the University of Genoa announced their AutoCRAT-acknowledged paper was published on September 4th, 2021. The open-access study entitled ‘Role of extracellular vesicles from adipose tissue- and bone marrow-mesenchymal stromal cells in endothelial proliferation and chondrogenesis’ appears in STEM CELLS Translational Medicine. DOI: 10.1002/sctm.21-0107 Download the PDF here.

Congratulations to the whole team!

UNIGE announces third AutoCRAT-acknowledged publication!2021-09-06T07:30:10+00:00

University Medicine Essen partners co-author AutoCRAT publication

Congratulations are in order! Authors Simon Staubach, Fabiola Nardi Bauer, Tobias Tertel, Verena Börger, Oumaima Stambouli, Denise Salzig, and Bernd Giebel published: Scaled preparation of extracellular vesicles from conditioned media in Advanced Drug Delivery Reviews, Volume 177, October 2021, 113940.  

Abstract

Extracellular vesicles (EVs) especially of mesenchymal stem/stomal cells (MSCs) are increasingly considered as biotherapeutic agents for a variety of different diseases. For translating them effectively into the clinics, scalable production processes fulfilling good manufacturing practice (GMP) are needed. Like for other biotherapeutic agents, the manufacturing of EV products can be subdivided in the upstream and downstream processing and the subsequent quality control, each of them containing several unit operations. During upstream processing (USP), cells are isolated, stored (cell banking) and expanded; furthermore, EV-containing conditioned media are produced. During downstream processing (DSP), conditioned media (CM) are processed to obtain concentrated and purified EV products. CM are either stored until DSP or are directly processed. As first unit operation in DSP, clarification removes remaining cells, debris and other larger impurities. The key operations of each EV DSP is volume-reduction combined with purification of the concentrated EVs. Most of the EV preparation methods used in conventional research labs including differential centrifugation procedures are limited in their scalability. Consequently, it is a major challenge in the therapeutic EV field to identify appropriate EV concentration and purification methods allowing scale up. As EVs share several features with enveloped viruses, that are used for more than two decades in the clinics now, several principles can be adopted to EV manufacturing. Here, we introduce and discuss volume reducing and purification methods frequently used for viruses and analyze their value for the manufacturing of EV-based therapeutics.

DOI: https://doi.org/10.1016/j.addr.2021.113940 Download the PDF here.

University Medicine Essen partners co-author AutoCRAT publication2021-08-30T12:21:06+00:00

Meet the Women in AutoCRAT: Leiden University Medical Center’s team

Prof. Ingrid Meulenbelt

Prof. Yolande F.M. Ramos

Danielle Nicholson, Pintail Limited spoke with Leiden University Medical Center Profs. Ingrid Meulenbelt and Yolande F. M. Ramos via Zoom to kick off our series of interviews with women researchers in AutoCRAT.

Danielle: Ingrid, Yolande, thank you for agreeing to speak with me about your work and congratulations on the publication of your recent paper. That’s really exciting news and very important for AutoCRAT.

Danielle: What is your assessment of the current state of osteoarthritis (OA) treatment and care?

Ingrid: It’s quite poor. There’s not much out there for people with OA. They are suffering from pain and problems in mobility already at 55 years of age and onwards. There is nothing for them yet so they are being almost patronized by the offer of physiotherapy and then painkillers. They are kept in a patched-up state until they are eligible for joint replacement surgery from about 70 years of age. This is currently the only disease-modifying treatment that we have right now. I think particularly the people with OA between 55 to 70-years of age who are still part of the workforce do not have any real options. In that respect, care is minimal. We know this from our patient and public participation arthritis group (PPA-Leiden). These people are searching the web for any treatment out there, something that they can do themselves. There is a lot of false hope.

Danielle: Why did you establish the PPA group?

Ingrid: Initially, it was the funding agencies in the Netherlands who believed that it was important to involve patients in research project design. But once we started the PPA group, we realized it was a highly valuable exercise for us and for the PhD students to engage with the patients because we are not medical doctors. The group provides an additional dimension to the work we are doing. This is an enrichment forwards and back. The group helps us to communicate our fundamental research, especially our abstract -omics work, in an understandable way.

Danielle: With regards to your recent publication, “Cartilage from human‑induced pluripotent stem cells: comparison with neo‑cartilage from chondrocytes and bone marrow mesenchymal stromal cells” Cell and Tissue Research, July 9th, 2021 its graphic (below) gives a helpful snapshot of the study design. It is a great tool to communicate the results to non-specialists.

Ingrid: It also helps us make the protocol for the medical ethical committee which inputs into the patient information leaflet.

Danielle: Can you please talk a bit about your research group and your roles within it? Where are you situated?

Ingrid: I’m the Head of the OA Research Group at the LUMC. Yolande is the most senior researcher in my lab and in that respect, she is also partly in charge of the staffing and guides the PhD students. She also does research in the lab. She is my right hand in that respect.

We are situated in the Research Tower next to the LUMC. In the OA Group, apart from Yolande, there are 3 more senior researchers, and we have 7 PhD students and a technician. We are situated within the Biomedical Data Science Department, a result of my background in genetic epidemiology. I started off trying to determine the genes that are causing OA. We gained an in-depth understanding of this in part due to the benefit of the data science people around us. When we identified a couple of the genes that we thought were interesting and could be involved in the underlying pathophysiology of OA we shifted focus to try to determine the function of these genes. What were these genes doing in the cartilage tissue? This work made us realise if you want to do functional work you need tissues to work with. This was why we started the Research in Articular Artrose Kraakbeen RAAK study, for OA articular cartilage research: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0103056). Because we are near the hospital, we can obtain materials from people that undergo joint replacement surgery as a result of OA. If a patient is undergoing joint replacement surgery in the morning, we get a call when the surgery is finished. From the surgical waste material, we can obtain cartilage and bone, but also cells. We create molecular profiles from the cartilage and bone, as in AutoCRAT, and with the cells, we generate disease models. We tried to regenerate cartilage and bone from the cells that we took from the patients. Because we wanted a more sustainable source of cells, we started with stem cell research, employing Yolande’s cell biology expertise. We evolved from a molecular, cellular, and genetic epidemiological group to a much more fundamental biological group. This combination of molecular epidemiology, -omics and cell biology has made our OA group stronger in research proposals. In AutoCRAT, we use our cell biology expertise with stem cells and combine this with -omics data to determine the mechanisms of action of the cells involved.

Danielle: What is your favourite aspect of your work?

Yolande: My work is very diverse: there is never a dull moment. No two days are ever the same. One day, I could take part in an interview, another I am talking to patients. Then, I am going to the lab to check my cells. I never have the same day twice. Science fascinates me, and as a result, the work is fulfilling.

Ingrid: Our work is dynamic and you are at the forefront of what is known, but the pitfall of what we do is that the work is never finished!

Danielle: The LUMC are ahead of the cellular therapeutics curve in many ways. What are some practical hurdles that must be overcome to make cell therapies widely available?

Ingrid: I try not to think too much about it yet. If you are realistic, and you speak with other people then we have a long way to go. Our OA group are still working quite fundamentally in that sense. As soon as we think about cell therapies with iPSCs, we need to have GMP facilities, GMP cells, cleanrooms and the regulatory rules! It is unbelievable what we must do. This is not something we can do as a small group.

As for the new centre, ​​NECSTGEN (Netherlands Centre for the Clinical Advancement of Stem Cell and Gene Therapies), it is being built. It is a large institute. The idea is beautiful- a forward-planning institute, nearby, linked to LUMC and that could take care of the facilities and legislation that we would need for human studies and therapies.

Yolande: In research such as in AutoCRAT, one uses a lot of animal-derived reagents. When you shift to developing a therapy for humans, as part of the GMP and because we are accustomed to the animal-derived reagents, the alternative reagents could make the experiments and therapies much more expensive. This is another hurdle.

Danielle: In your opinion what is the most exciting aspect of AutoCRAT?

Yolande: For me, it is really exciting that so many partners within Europe aim at one same research goal. Together, we combine knowledge capacity and practical expertise to arrive at one outcome- for the patient. There is a really good synergy among the partners, and this helps to advance toward this aim together!

Ingrid: I agree, and indeed, the project has a very open atmosphere without any competition, we are pushing forward and aiming for that one goal! There is always competition going on in the field, at various levels. Mary is doing a good job to connect us and make sure we are collaborating without being protective of the work we are doing.

Danielle: What do you like to do in your free time in and around Leiden?

Ingrid: Well, I do not live in Leiden but close by, near the sea. I really enjoy being by the shore, running near the dunes and enjoying these things with everyone I love.

Yolande: I live in Amsterdam. I just love the cultural environment there. I love visiting museums on the weekends, walking around Amsterdam, enjoying the architecture and the parks.

Danielle: Do you have any advice for Early Stage Researchers looking to get into cell therapy research?

Ingrid: Don’t let others get you down. Don’t let yourself get too distracted by the grant-writing and all of the other things you will need at the end. Enjoy the dynamics of the field.

Danielle: Thank you both for meeting with me and sharing your thoughts. This is the next best thing to a face-to-face meeting which I hope will happen before too long passes!

Meet the Women in AutoCRAT: Leiden University Medical Center’s team2021-10-28T19:46:08+00:00

LUMC publishes the first AutoCRAT-acknowledged study!

Congratulations to the team of Alejandro Rodríguez Ruiz, Amanda Dicks, Margo Tuerlings, Koen Schepers, Melissa van Pel, Rob G. H. H. Nelissen, Christian Freund, Christine L. Mummery, Valeria Orlova, Farshid Guilak, Ingrid Meulenbelt, and Yolande F. M. Ramos! Their study entitled “Cartilage from human‑induced pluripotent stem cells: comparison with neo‑cartilage from chondrocytes and bone marrow mesenchymal stromal cells” was published open-access in the journal Cell and Tissue Research on July 9th, 2021.

Download the paper here.

LUMC publishes the first AutoCRAT-acknowledged study!2021-07-12T14:01:29+00:00
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