News

Solid fraction determines stiffness and viscosity in decellularized pancreatic tissues
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The article „Solid fraction determines stiffness and viscosity in decellularized pancreatic tissues“ in Biomaterials Advances is now available online.
There is free access to a PDF of the article here until August 20, 2022!

The role of extracellular matrix (ECM) composition and turnover in mechano-signaling and the metamorphic fate of cells seeded into decellularized tissue can be elucidated by recent developments in non-invasive imaging and biotechnological analysis methods. Because these methods allow accurate quantification of the composition and structural integrity of the ECM, they can be critical in establishing standardized decellularization protocols. This study proposes quantification of the solid fraction, the single-component fraction and the viscoelasticity of decellularized pancreatic tissues using compact multifrequency magnetic resonance elastography (MRE) to assess the efficiency and quality of decellularization protocols. MRE of native and decellularized pancreatic tissues showed that viscoelasticity parameters depend according to a power law on the solid fraction of the decellularized matrix. The parameters can thus be used as highly sensitive markers of the mechanical integrity of soft tissues. Compact MRE allows consistent and noninvasive quantification of the viscoelastic properties of decellularized tissue. Such a method is urgently needed for the standardized monitoring of decellularization processes, evaluation of mechanical ECM properties, and quantification of the integrity of solid structural elements remaining in the decellularized tissue matrix.

Authors are Joachim Snellings, Eriselda Keshi, Peter Tang, Assal Daneshgar, Esther C. Willma, Luna Haderer, Oliver Klein, Felix Krenzien, Thomas Malink, Patrick Asbach, Johann Pratschke, Igor M. Sauer, Jürgen Braun, Ingolf Sack, and Karl Hillebrandt.

Inaugural Lectures
We are pleased to announce that four members of staff have successfully completed their habilitation work in the last few months!

On
Friday, 08.07.2022 at 15:00 in lecture hall 3 of the teaching building (Forum 3, CVK), Dr. med. habil. Linda Feldbrügge and Dr. med. habil. Paul Ritschl will give their inaugural lectures entitled "New role of surgery in modern tumour and transplant medicine".

On
Friday, 15.07.2022 at 16:30 in the Friedrich Kopsch lecture theatre of the Anatomy Department at Campus Mitte Dr. med. habil. Eva Dobrindt and Dr. med. habil. Rosa Schmuck will present their inaugural lectures with the topic "An Operating Room of One's Own - The Surgeon in Ancient Tradition and Modernity".
This will be followed by a small reception in the park in front of the venue.
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Si-M | Topping-out Ceremony
Today, representatives of Charité – Universitätsmedizin Berlin and Technische Universität Berlin celebrated the topping-out ceremony for the research building "Der Simulierte Mensch" (Si-M, "The Simulated Human") together with political representatives. Guests included the Governing Mayor Franziska Giffey, Senator for Health and Science and Charité Supervisory Board Chair Ulrike Gote and Finance Senator Daniel Wesener.

We are very excited: this will be a great building with even greater content.

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Tissue Engineering for the Diaphragm
"Tissue Engineering for the Diaphragm and its Various Therapeutic Possibilities – A Systematic Review" is available here in Advanced Therapeutics (open access).

Diaphragmatic impairments exhibit high morbidity as well as mortality while current treatment options remain unsatisfactory. Tissue engineering (TE) approaches have explored the generation of an optimal biocompatible scaffold for diaphragmatic repair through tissue decellularization or de novo construction, with or without the addition of cells. The authors conducted a systematic review on the current state of the art in diaphragmatic tissue engineering (DTE) and found 24 articles eligible for final synthesis. The included approaches studied decellularization-based graft generation and de novo bioscaffold construction. Three studies focused on in vitro host-scaffold interaction with synthesized, recellularized grafts and decellularized extracellular matrix scaffolds. Another three studies investigated evaluation tools for decellularization efficacy. Among all studies, recellularization is performed in both decellularization-based and de novo generated scaffolds. De novo constructed biocomposites as well as decellularized and recellularized scaffolds induced pro-regenerative remodeling and recovery of diaphragmatic function in all examined animal models. Potential therapeutic applications comprise substance defects requiring patch repair, such as congenital diaphragmatic hernia, and functional diseases demanding an entire organ transplant, like muscular dystrophies or dysfunction after prolonged artificial respiration.

Autors are Agnes K. Boehm, Karl H. Hillebrandt, Tomasz Dziodzio, Felix Krenzien, Jens Neudecker, Simone Spuler, Johann Pratschke, Igor M. Sauer, and Marco N. Andreas.
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Detection of nicotinamide adenine dinucleotide (NAD) in cells and blood plasma
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Priv,-Doz. Dr. med. Felix Krenzien and Dr. Jennifer Kirwan (Technologieplattform Metabolomik, Max-Delbrück-Centrum für Molekulare Medizin, Berlin) successfully applied for a grant within the Else Kröner Fresenius Stiftung funding line: Translational Research.

Recently, the molecule nicotinamide adenine dinucleotide (NAD) has attracted attention as it is involved in various important regulatory mechanisms, immune signaling, aging and regenerative processes. In this regard, it occupies key positions in many redox reactions of the body due to its role as a redox couple (NAD as an oxidized species and NADH as a reduced species). Consequently, NAD homeostasis (the maintenance of NAD in cells) is considered essential. The scientific consensus for many years was that the oxidized species resides exclusively in the intracellular milieu (iNAD). However, recent findings indicate that NAD also exists extracellularly (eNAD) and it is present in virtually all body fluids (from lymph to saliva to blood plasma). Based on these findings, precursors of NAD have recently been approved by the FDA and are commercially available. Measurement of eNAD in blood plasma is problematic due to its low concentration in the nanomolar range. However, quantifying eNAD plasma levels but also eNAD concentrations in cells is necessary to monitor the intake of NAD or its precursors and to adjust their dosage precisely.
The primary objective of this project is to validate, bioanalyze,and to document the assay for eNAD according to the ICH-M10 guidance document endorsed by the U. S. Food and Drug Administration (FDA). Adherence to the principles presented in this guideline should improve the quality and consistency of bioanalytical data, thereby supporting assay development and market approval. In addition, the assay will also be established for the measurement of intracellular NAD (iNAD), and validation of iNAD quantification will also be performed according to the guideline.

In the second part of the project, a clinical study will be conducted to determine whether the intake of nicotinamide riboside (precursor of NAD) leads to a change in eNAD and iNAD. Thus, the basis for an indication-dependent bioanalysis of the measurement of NAD will be developed to monitor the intake of NAD and its precursor or to adjust the dosage specifically on the basis of the quantification.
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Development of human-based hydrogels as a substitute for mouse-derived Matrigel for cancer research
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With a new funding line, Charité 3R wants to support the development of animal-free cell cultures at Charité.

For in vitro cancer research, mini-tumours are grown in a gel-like cultivation structure that serves the three-dimensional growth of the mini-tumours. This gel-like cultivation substance is obtained from mouse tumours, an unnatural cultivation environment for human mini-tumours. The aim of the project "Development of human-based hydrogels as a substitute for mouse-derived Matrigel for cancer research" by Björn Papke from the Institute of Pathology and Karl Hillebrandt is to produce a cultivation structure without animal additives. For this purpose, a cultivation structure, also gel-like, is to be produced from tissue obtained from patients during surgical procedures, which better corresponds to the natural environment of the human mini-tumours.


Congratulations!
Dr. med. Hannah Everwien
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Hannah Everwien successfully defended her doctoral thesis entitled "Construction of a neo-pancreas by means of decellularisation and recellularisation" (summa cum laude)!

Congratulations!

Robert-Koch-Prize awarded to Simon Moosburner
Today, Dr. med. Simon Moosburner received the Robert-Koch-Prize for one of the three best dissertations of the Charité - Universitätsmedizin Berlin in 2020 for his thesis titled  "Erweiterung der Spenderpopulation bei Lebertransplantation: Klinischer Bedarf und Entwicklung eines Kleintier-Lebermaschinenperfusionssystems (Expanding the donor pool for liver transplantation: clinical need and development of small animal liver perfusion system)".


Congratulations!
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BIH Charité Clinician Scientist Symposium in Honor and Memory of Duška Dragun
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28 May 2021 - 29 May 2021
BIH Charité Clinician Scientist Symposium in Honor and Memory of Duška Dragun

The symposium is composed of several components: First and foremost, it will commemorate Prof. Duška Dragun, the former Director of the BIH Biomedical Innovation Academy (BIA) and Director of the BIH Charité Clinician Scientist Program, who passed away in December 2020, and will be joined by stakeholders from academia and science policy. In addition, there will be scientific sessions, which will form tandems of program fellows and invited speaker. During a digital certificate ceremony on the evening of 28 May 2021, some 50 alumni will be bid farewell. The event language is English.

When
28 and 29 May 2021
10:00 - 6:30 pm

How
Online Event (semi-digital)

Registration
To receive the login link please register here.
Advanced Clinician Scientists
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Priv.-Doz. Dr. Nathanael Raschzok and Priv.-Doz. Dr. Felix Krenzien successfully applied for the BIH Charité Advanced Clinician Scientist Pilot Programme (AdCSP) in a highly competitive process.

The BIH Charité AdCSP is designed as a career-phase-specific, sustainable funding programme that aims to closely interlink individual and institutional funding. The primary goal of the programme is to simultaneously incentivise the fellows and recognise the permissive academic culture of the respective clinics or institutes. Like the BIH Charité Clinician Scientist Programme (CSP) and the "Digital Clinician Scientist Programme" (DCSP), which has been additionally funded by the DFG since 2019, it is intended to be open to all clinical disciplines and to offer multiple networking opportunities for the funded fellows and participating clinics and institutes.

Congratulations!
Recellularization of decellularized bovine carotid arteries
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"In vitro recellularization of decellularized bovine carotid arteries using human endothelial colony forming cells" was published in the latest issue of Journal of Biological Engineering.
Many patients suffering from peripheral arterial disease (PAD) are dependent on bypass surgery. However, in some patients no suitable replacements (i.e. autologous or prosthetic bypass grafts) are available. Advances have been made to develop autologous tissue engineered vascular grafts (TEVG) using endothelial colony forming cells (ECFC) obtained by peripheral blood draw in large animal trials. Clinical translation of this technique, however, still requires additional data for usability of isolated ECFC from high cardiovascular risk patients.
Bovine carotid arteries (BCA) were decellularized using a combined SDS (sodium dodecyl sulfate) -free mechanical-osmotic-enzymatic-detergent approach to show the feasibility of xenogenous vessel decellularization. Decellularized BCA chips were seeded with human ECFC, isolated from a high cardiovascular risk patient group, suffering from diabetes, hypertension and/or chronic renal failure. ECFC were cultured alone or in coculture with rat or human mesenchymal stromal cells (rMSC/hMSC). Decellularized BCA chips were evaluated for biochemical, histological and mechanical properties. Successful isolation of ECFC and recellularization capabilities were analyzed by histology.

Decellularized BCA showed retained extracellular matrix (ECM) composition and mechanical properties upon cell removal. Isolation of ECFC from the intended target group was successfully performed (80% isolation efficiency). Isolated cells showed a typical ECFC-phenotype. Upon recellularization, co-seeding of patient-isolated ECFC with rMSC/hMSC and further incubation was successful for 14 (n = 9) and 23 (n = 5) days. Reendothelialization (rMSC) and partial reendothelialization (hMSC) was achieved. Seeded cells were CD31 and vWF positive, however, human cells were detectable for up to 14 days in xenogenic cell-culture only. Seeding of ECFC without rMSC was not successful.

Using our refined decellularization process we generated easily obtainable TEVG with retained ECM- and mechanical quality, serving as a platform to develop small-diameter (< 6 mm) TEVG. ECFC isolation from the cardiovascular risk target group is possible and sufficient. Survival of diabetic ECFC appears to be highly dependent on perivascular support by rMSC/hMSC under static conditions. ECFC survival was limited to 14 days post seeding.
Authors are N. Seiffert, P. Tang, E. Keshi, A. Reutzel-Selke, S. Moosburner, H. Everwien, D. Wulsten, H. Napierala, J. Pratschke, I.M. Sauer, K. Hillebrandt, and B. Struecker.
J Biol Eng 15, 15 (2021). https://doi.org/10.1186/s13036-021-00266-5
Position for Research Associate / Research Fellow
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Priv.-Doz. Dr. Nathanael Raschzok and his team are working on strategies for (re-) conditioning of marginal liver grafts by ex vivo liver machine perfusion. The aim for the proposed job offer, which is funded by grants of the Else Kröner-Fresenius-Stiftung, is to make steatotic liver grafts, which are usually discarded from transplantation due to the high risk for the recipient, acceptable for transplantation. We have already established a small animal model of ex vivo liver machine perfusion as well as transplantation. Aim of this project is to test a clinically approved drug in dose-response studies (based on preliminary data), followed by in vivo studies in the rat liver transplantation model.

Your responsibility will be:
  • Organ perfusion of murine livers in our established small animal modell for ex vivo liver machine perfusion
  • Support of in rat liver transplantation experiments
  • Organ recovery and transplantation (not mandatory)
  • Biochemical analysis of the perfusat and the lipid metabolism (ELISA), tissue analysis (qRT-PCR, Wester Blot, immunochemistry, immunofluorescence)
  • We fully support the application and submission of a doctoral thesis (e.g. Dr. rer.medic or MD/PhD)
Require­ments
  • Degree in biology, biochemistry, biotechnology or medicine
  • Pevious experience in molecular cell biology and/or proteinbiochemistry, or surgical research
  • Proficiency in standard methods, especially histology, immunhistochemistry, qPCR, FACS, microscopy, cell culture/cell isolation
  • Excellent english language skills
Personal characteristics
  • innovative spirit and extraordinary motivation, interest in purposeful work
  • team work orientated
  • organized, ability for analytic and independent work ethic

If you're the right person: please send all application documents, e.g. cover letter, curriculum vitae, certificates, attestations, etc. to the following address, quoting the reference number by e-mail to
Charité – Universitätsmedizin Berlin
Chirurgische Klinik, Exp. Chirurgie
z.Hd. PD Dr. Nathanael Raschzok
Augustenburger Platz 1
D-13353 Berlin
nathanael.raschzok@charite.de
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Si-M | Topping-out Ceremony
Today, representatives of Charité – Universitätsmedizin Berlin and Technische Universität Berlin celebrated the topping-out ceremony for the research building "Der Simulierte Mensch" (Si-M, "The Simulated Human") together with political representatives. Guests included the Governing Mayor Franziska Giffey, Senator for Health and Science and Charité Supervisory Board Chair Ulrike Gote and Finance Senator Daniel Wesener.

We are very excited: this will be a great building with even greater content.

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Si-M | Topping-out Ceremony
Today, representatives of Charité – Universitätsmedizin Berlin and Technische Universität Berlin celebrated the topping-out ceremony for the research building "Der Simulierte Mensch" (Si-M, "The Simulated Human") together with political representatives. Guests included the Governing Mayor Franziska Giffey, Senator for Health and Science and Charité Supervisory Board Chair Ulrike Gote and Finance Senator Daniel Wesener.

We are very excited: this will be a great building with even greater content.

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