Project news

Jason Hunt

My name is Jason Hunt and I am originally from Clonakilty, Co. Cork. I have always been interested in bioprocessing and have a Bachelor of Science in Microbiology. I am currently undergoing an MSc in Cell Manufacturing and Therapy at the National University of Ireland Galway (NUIG). I started the course last September and have been doing it from home since lockdown. I enjoyed learning about the various cell therapies currently in development, including a lot of the work being carried out at the Regenerative Medicine Institute (REMDI) based in NUI Galway. One of the talks I was most interested in was automated platforms for cell manufacturing given by Prof. Murphy where I first stumbled across AutoCRAT. I was really interested in the project and was immediately drawn to the work that was being carried out. A little while later, a PhD opportunity became available in Prof. Murphy’s lab working on this project which I quickly applied for. I have recently joined the AutoCRAT as part of placement for my course and plan to continue working on this project as PhD student once the summer ends.

Currently, my work involves monitoring the differentiation of iPSCs into iMSCs using PCR. The ultimate goal of this project is to characterize the differentiation process which will then be used to develop an in-line qPCR assay. This will allow us to monitor the differentiation process from iPSCs to iMSCs within the automated platform which will help to ensure the production of a consistent product while also ensuring any mistakes in the process are detected early. Fortunately, my time in the lab has not been too limited. I have always been able to use the lab when needed. Although my interactions with other members of REMEDI have been limited due to Covid restrictions, I am sure I will be able to become more acquainted with my fellow colleagues once lockdown restrictions ease.

Aside from college, the rest of my time is largely taken up by staying active in the gym. While this has primarily been replaced with walking since the lockdown began. However, I hope to get back into being more active as the restrictions ease and the gyms reopen.

Ferdinand Biermann

For the International Society for Stem Cell Research (ISSCR) virtual meeting, June  21-26, 2021, AutoCRAT partners at Fraunhofer IPT were invited by Eppendorf AP (https://www.eppendorf.com/worldwide/) to deliver a talk as part of their June 21st afternoon focus session, ‘Improving Reproducibility and Scaling-Up of Stem Cell Cultures.’

Speaking at this high-profile event, Ferdinand Biermann, Fraunhofer IPT will describe the AutoCRAT platform, the bioreactor layout and our planned integration of the Eppendorf reactor.

Download the June 21, 2021 event programme here.

Prof. Dr Bernd Giebel, University Medicine Essen

Within AutoCRAT, two research groups work on the EV-based therapeutic development for the modulation of osteoarthritis: Prof. Dr Bernd Giebel heads a research group within the University Medicine Essen’s Institute for Transfusion Medicine. As an expert in early human haematopoiesis and extracellular vesicles (EV) research, his group focusses on human hematopoietic stem cell biology and the therapeutic potential of mesenchymal stem/stromal cell-derived EVs. Prof. Chiara Gentili’s research team in the Department of Experimental Medicine (DIMES) at the Università degli Studi di Genova brings decades of experience with pre-clinical models for regenerative medicine and expertise in MSC and EV production for the treatment of osteoarthritis.

At the turn of the millennium, mesenchymal stromal cells (MSCs), became popular research entities in regenerative medicine. Aiming to apply allogeneic off-the-shelf MSC products for acute conditions, like myocardial infarction and ischemic stroke, researchers began studying the interaction of allogenic MSCs with components of the immune system and showed that they exert immunomodulatory functions [1, 2]. Regarding their pro-regenerative and immunomodulatory potentials, up to now, MSCs have been applied in more than a thousand clinical trials to various patient cohorts (www.clinicaltrials.gov), some confirming their therapeutic potential, others failing to show efficacy [3].

Prof. Chiara Gentili, Università degli Studi di Genova

As most systemically administered MSCs are recovered in the lungs of recipients and hardly in affected tissues, the long-lasting dogma that MSCs act in a cell replacement role became challenged. Quickly, researchers postulated that they mainly act in a paracrine cell-to-cell communication capacity [4, 5]. After confirming that MSC conditioned media exerted comparable therapeutic effects to administered cells [6-8], several groups began to search for active components in MSC conditioned media. The groups of Giovanni Camussi and Sai Kiang Lim showed in 2009 and 2010 that MSCs’ therapeutic activity was recovered in vesicle enriched culture media fractions [9, 10]. After defining microvesicles as budding from the plasma membrane and exosomes as derivatives of the endosomal compartment, and because different vesicular entities cannot yet be experimentally separated from each other, the scientific community agreed in experimental settings to the use of the term extracellular vesicles (EVs) instead of more specified terms [11, 12]. Using EVs for therapeutic purposes has many advantages over cells. For example, EV-based therapeutics are easier to handle and can be separated by filtration [13]. In recent years, the therapeutic EV field has grown exponentially. MSC-EV products, like their parental cells, modulate immune responses in animal models and have been efficaciously used to treat an otherwise treatment-resistant human with Graft-versus-Host Disease [14, 15].

Meanwhile, many groups approach the clinic intending to apply MSC-EV products to different patient cohorts including those with COVID-19 [16]. Although pre-clinical data are very encouraging and MSC-EVs, in principle, provide promising therapeutic agents for the future, several translation challenges remain. For now, production protocols are not standardized, and apparently, not all MSCs are competent in releasing therapeutically active EVs [13, 16-18]. Despite reports that MSC-EVs possess immunomodulatory, pro-regenerative, pro-angiogenic and/or anti-apoptotic properties, their precise mechanisms of action remain unclear. Collaborative research as in AutoCRAT is required to improve MSC-EV production platforms and to explore the MSC-EV’s therapeutic potential to warrant effective translation into the clinic [19, 20].

References:

1. Di Nicola, M., et al., Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 2002. 99(10): p. 3838-43.
2. Bartholomew, A., et al., Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Experimental hematology, 2002. 30(1): p. 42-8.
3. Galipeau, J. and L. Sensebe, Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. Cell Stem Cell, 2018. 22(6): p. 824-833.
4. Caplan, A.I. and J.E. Dennis, Mesenchymal stem cells as trophic mediators. Journal of cellular biochemistry, 2006. 98(5): p. 1076-84.
5. Caplan, A.I., Mesenchymal Stem Cells: Time to Change the Name! Stem Cells Transl Med, 2017. 6(6): p. 1445-1451.
6. Gnecchi, M., et al., Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. The FASEB journal: official publication of the Federation of American Societies for Experimental Biology, 2006. 20(6): p. 661-9.
7. Gnecchi, M., et al., Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nature medicine, 2005. 11(4): p. 367-8.
8. Timmers, L., et al., Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res, 2007. 1(2): p. 129-37.
9. Bruno, S., et al., Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol, 2009. 20(5): p. 1053-67.
10. Lai, R.C., et al., Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res, 2010. 4(3): p. 214-22.
11. Gould, S.J. and G. Raposo, As we wait: coping with an imperfect nomenclature for extracellular vesicles. J Extracell Vesicles, 2013. 2.
12. Thery, C., et al., Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles, 2018. 7(1): p. 1535750.
13. Lener, T., et al., Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper. J Extracell Vesicles, 2015. 4: p. 30087.
14. Giebel, B., L. Kordelas, and V. Borger, Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles. Stem Cell Investig, 2017. 4(10): p. 84.
15. Börger, V., et al., Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles and Their Potential as Novel Immunomodulatory Therapeutic Agents. Int J Mol Sci, 2017. 18(7).
16. Börger, V., et al., ISEV and ISCT statement on EVs from MSCs and other cells: considerations for potential therapeutic agents to suppress COVID-19. Cytotherapy, 2020.
17. Witwer, K.W., et al., Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J Extracell Vesicles, 2019. 8(1): p. 1609206.
18. Reiner, A.T., et al., Concise Review: Developing Best-Practice Models for the Therapeutic Use of Extracellular Vesicles. Stem Cells Transl Med, 2017. 6(8): p. 1730-1739.
19. Weiss, D.J., et al., Weiss Response to Sengupta et al. (DOI: 10.1089/scd.2020.0095). Stem Cells and Development, 2020. 29(24): p. 1533-1534.
20. Lim, S.K., et al., Re: “Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19” by Sengupta et al. Stem Cells Dev, 2020.

Adjusting to the ‘new normal’ has left several enjoyable aspects of life a challenge for many. PI Prof. Dr Ingrid Meulenbelt of Leiden University Medical Center conducted her osteoarthritis (OA) public and patients in research (PPI) group via Zoom yesterday, February 24, 2021. At this first meeting since COVID-19 ravaged the world, the group of ten seemed very happy to talk together again. Similar to everybody who is less mobile and bound to home, they are lonely.

The group typically met in person every two to three months in Leiden to discuss research on OA within and outside the group. They work as a team to offer mutual help with research proposals and to prioritize gaining broad societal support for research. Participants have adapted to the current situation but had a great deal to discuss, mainly the points below as prepared by Prof. Dr Meulenbelt. It is such welcome news that PPI groups have adapted and are meeting again!

Join AutoCRAT partners at NUI Galway as they host the webinar “Real-Time Near Infrared Fluorescence Imaging Research Tools With The Potential For Clinical Use” on December 10, 2020, at 2 pm GMT. 

Click here for free registration:  https://attendee.gotowebinar.com/register/2047840817639953935

Fluorescence-guided surgery, a real-time intraoperative navigation modality, enables surgeons to precisely discriminate boundaries between lesions and healthy tissue.

In this webinar, Prof. O’Shea of the Royal College of Surgeons in Ireland will present research on a novel class of NIR-fluorophores (BF2-azadipyrromethene) as an attractive tool for the identification of different anatomical features. In addition, this fluorophore has also shown high biocompatibility and labelling efficiency with human cells and their-derived extracellular vesicles (EVs). This valuable feature further supports its application in cell and EV tracking analysis for both in vivo and in vitro.

If you have any questions about the webinar, please contact Dr Maojia Xu by email at .

Prof Dr Bernd Giebel, University Hospital Essen

At the virtual International Society of Liquid Biopsy (ISLB) conference on Friday, October 30th, 2020, Prof Dr Bernd Giebel of the University Hospital Essen (www.uk-essen.de) will deliver a presentation acknowledging AutoCRAT. This talk entitled “Mesenchymal Stem Cell-derived Extracellular Vesicles, a novel Tool in Regenerative Medicine” will be broadcast to attendees on Friday, October 30th as part of the ISLB – ISEV joint session in Extracellular Vesicles. Find the entire conference programme here.