2:06 for 25km – Congratulations!

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Cells isolated from diseased explanted livers

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The International Journal of Artificial Organs (official journal of the European Society for Artificial Organs [ESAO]) published our paper on Isolation, characterization and cold storage of cells isolated from diseased explanted livers. Authors are Belaschk E, Rohn S, Mukiibi R, Reutzel-Selke A, Tang P, Sawitzki B, Pratschke J, Sauer IM and Mogl MT.

Livers discarded after standard organ retrieval are commonly used as a cell source for hepatocyte transplantation. Due to the scarcity of organ donors, this leads to a shortage of suitable cells for transplantation. Here, the isolation of liver cells from diseased livers removed during liver transplantation is studied and compared to the isolation of cells from liver specimens obtained during partial liver resection.
Hepatocytes from 20 diseased explanted livers (Ex-group) were isolated, cultured and stored at 4°C for up to 48 hours, and compared to hepatocytes isolated from the normal liver tissue of 14 liver lobe resections (Rx-group). The nonparenchymal cell fraction (NPC) was analyzed by flow cytometry to identify potential liver progenitor cells, and OptiPrep™ (Sigma-Aldrich) density gradient centrifugation was used to enrich the progenitor cells for immediate transplantation.
There were no differences in viability, cell integrity and metabolic activity in cell culture and survival after cold storage when comparing the hepatocytes from the Rx-group and the Ex-group. In some cases, the latter group showed tendencies of increased resistance to isolation and storage procedures. The NPC of the Ex-group livers contained considerably more EpCAM+ and significantly more CD90+ cells than the Rx-group. Progenitor cell enrichment was not sufficient for clinical application.
Hepatocytes isolated from diseased explanted livers showed the essential characteristics of being adequate for cell transplantation. Increased numbers of liver progenitor cells can be isolated from diseased explanted livers. These results support the feasibility of using diseased explanted livers as a cell source for liver cell transplantation.

Int J Artif Organs. 2017 May 23:0. doi: 10.5301/ijao.5000594. [Epub ahead of print]

ECRT Kickbox – Advanced Scientist Grant

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PD Dr. Nathanael Raschzok receives one of the 2017 Einstein Center for Regenerative Therapies (ECRT) Kickbox – Advanced Scientist Grant.
Einstein Center for Regenerative Therapies Kickbox – advanced scientist grant. The project is entitled „Overcoming steatotic compromise – Reconstitution of endogenous repair in severely steatotic liver grafts by metabolic reconditioning“. The project will be conducted by Nathanael Raschzok, Angelika Kusch, Duska Dragun, and Igor M. Sauer.

In order to stimulate excellent and creative research ideas that might take regenerative therapies a vital step forward, the Einstein Center offers a special two-stage funding scheme.
At first, the Kickbox seed grant provides a great framework to investigate initial ideas and to develop sound research concepts. Subsequently, the flexible funds enable the realisation of projects that evolved from the Kickbox initiation phase in order to reach the scientific goals of the Einstein Center.

Congratulations!

Magnetic field and cells labeled with IO particles

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Our paper entitled "The magnetic field of magnetic resonance imaging systems does not affect cells labeled with micrometer-sized iron oxide particles," has been accepted for publication in Tissue Engineering, Part C: Methods. Authors are Martin Kluge, Annekatrin Leder, Karl H. Hillebrandt, Benjamin Struecker, Dominik Geisel, Timm Denecke, Rebeka D. Major, Anja Reutzel-Selke, Peter Tang, Steffen Lippert, Christian Schmidt, Johann Pratschke, Igor M. Sauer, and Nathanael Raschzok.

Labeling using iron oxide particles enables cell tracking via magnetic resonance imaging (MRI). However, the magnetic field can affect the particle-labeled cells. Here, we investigated the effects of a clinical MRI system on primary human hepatocytes labeled using micrometer-sized iron oxide particles (MPIOs).
HuH7 tumor cells were incubated with increasing concentrations of biocompatible, silica-based, micron-sized iron oxide-containing particles (sMPIO; 40 – 160 particles/cell). Primary human hepatocytes were incubated with 100 sMPIOs/cell. The particle-labeled cells and the native cells were imaged using a clinical 3.0-T MRI system, whereas the control groups of the labeled and unlabeled cells were kept at room temperature without exposure to a magnetic field. Viability, formation of reactive oxygen species, aspartate aminotransferase leakage, and urea and albumin synthesis were assessed over a culture period of 5 days.
The dose finding study showed no adverse effects of the sMPIO labeling on HuH7 cells. MRI had no adverse effects on the morphology of the sMPIO-labeled primary human hepatocytes. Imaging using the T1- and T2-weighted sequences did not affect the viability, transaminase leakage, formation of reactive oxygen species, or metabolic activity of the sMPIO-labeled cells or the unlabeled, primary human hepatocytes.
sMPIOs did not induce adverse effects on the labeled cells under the conditions of the magnetic field of a clinical MRI system.

PD Dr. N. Raschzok & PD Dr. A. Andreou

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Charité BIH Entrepreneurship Summit

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The Charité BIH Entrepreneurship Summit is a preeminent international cross-disciplinary forum for sharing and exploring the most important discoveries and emerging trends influencing the future of healthcare around the world.

Every year in May over 400 global leaders in healthcare innovation, including entrepreneurs, scientists, physicians, investors, policymakers, and business leaders convene at the Charité BIH Entrepreneurship Summit in the vibrant German capital of Berlin. We offer our participants a one-of-a-kind opportunity to meet with world-class specialists working at Charité & MDC, to build relationships with prominent international partners and experts working in the healthcare industry, and to help grow businesses.

This year's 10th Charité Entrepreneurship Summit will again take place at the Berlin-Brandenburg Academy of Sciences and Humanities on May 8 - 9, 2017. The Summit is significantly supported by the Berlin Institute of Health and focusses on 'Global Challenges of Healthcare'. Israel will be the official partner country for the Summit 2017. We are looking forward to learning more about the Israeli innovation & start-up culture, funding opportunities and challenges in Healthcare.

The Summit's two-day agenda will address a wide variety of topical issues including change of innovation culture, healthy aging & degenerative diseases, virtual reality and mental health. In addition, the Summit will seek to engage participants in lively discussions about business, science and the intersection of the two. Startups and Entrepreneurs are invited to apply for the LifeSciences VentureMarket, a platform to present their companies to a pool of international angels, venture investors, and corporate funds at this year's Summit.

You will find the program here.

BIH Paper of the Month...

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Benjamin Strücker, Hendrik Napierala and the rest of the team were awarded with the BIH Paper of the Month for their publication on a new method for developing a transplantable endocrine Neo-Pancreas.
The BIH Paper of the Month is awarded by the BIH Board of Directors to honor a special publication achievement from the joint research space of Charité and MDC. The Paper of the Month is sponsored by the Stiftung Charité as part of its Johanna Quandt Private Excellence Initiative.

H. Napierala, K.-H. Hillebrandt, N. Haep, P. Tang, M. Tintemann, J. Gassner, M. Noesser, H. Everwien, N. Seiffert, M. Kluge, E. Teegen, D. Polenz, S. Lippert, D. Geisel, A. Reutzel Selke, N. Raschzok, A. Andreou, J. Pratschke, I. M. Sauer & B. Struecker. Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans. Scientific Reports 7. Article number: 41777 (2017) doi:10.1038/srep41777

You may download the publication here.

Dr. Karl

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ECRT Kickbox – Junior Scientist Grant

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Karl Hillebrandt receives one of the 2017 Einstein Center for Regenerative Therapies (ECRT) Kickbox – Junior Scientist Grant. The project is entitled "Fighting liver cirrhosis? Establishment and analysis of decellularized human cirrhotic liver slices as a 3-dimensional model to study cell matrix interactions".

Liver cirrhosis is one of the main indications for liver transplantation. Due to the organ shortage, this therapy option is limited to the minority of patients suffering from cirrhosis. Therefore, there is a need of alternative treatment options.The aim of our project is to establish a decellularization protocol for human cirrhotic livers slices, which preserves the natural extracellular matrix (ECM) of cirrhotic livers. These decellularized liver slices will serve as a 3 dimensional model to study cell matrix interactions. If we are able to establish a protocol which will preserve the ECM, we will conduct in vitro recellularization experiments to study how the cirrhotic ECM will change the genotype and phenotype of different cell types. With this knowledge we aim to modify specific cell types in vivo or vitro for example prior to cell transplantation. Our ambition is to steer the cell matrix interaction via these modified cells after their transplantation and thereby halt or even reverse the progress of liver cirrhosis. This approach may offer an alternative treatment option in the future.
Team : Karl Hillebrandt, Oliver Klein, Ben Strücker, Igor Sauer

Congratulations!

imag|Ne surgery – April 28-29, 2017

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Einstein Center Digital Future – Opening



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Einstein Visiting Fellow Prof. Stefan G. Tullius


Prof. Dr. Stefan G. Tullius, Harvard Medical School, became Einstein BIH Visiting Fellow at the Charité, Department of Surgery.
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Vascular Composite Tissue Allotransplantation (VCA) has developed from a pioneering endevour to a clinical reality during the last 15 years. More than 150 extremity, face, knee, and most recently uterus and penis transplants have been performed during the last 15 years. VCA activities have been seen around the globe. Although feasibility of the procedure has been shown, it is still emerging and far from being a standard clinical procedure.

The Charité has been an international leader in transplantation research for decades. However, neither VCA basic clinical research programs are currently offered in Berlin or Germany in a meaningful way.The involvement of Prof. Tullius as an Einstein BIH Visiting Fellow is expected to synergize and accelerate efforts igniting both a clinical research transplant program and a basic research group of excellence. The overall objective of our integrated basic and clinical research working group Vascular Composite Tissue Transplantation has three main goals:

  1. To establish a basic Research group of Excellence: VCAs offer unique opportunities to study novel aspects of antigenicity, immune modulation and neo-vascularization. One important aspect that distinguishes VCA from solid organ transplants is their blood supply through a vascularized arterial in- and venous outflow in addition to sprouting new vessels at the large interface of VCA with recipient tissue.
  2. To establish a clinical bio-repository as a pre-requisite for a clinical research VCA program.
  3. To implement a clinical VCA research program (hand, abdominal wall, uterus) as a multi- disciplinary and translational effort.

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Forschungs-Colloquium I 2017

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Engineering an endocrine Neo-Pancreas

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Scientific Reports accepted our latest paper on „Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans“. Authors are H. Napierala, K. Hillebrandt, N. Haep, P. Tang, M. Tintemann, J. Gassner, M. Noesser, H. Everwien, N. Seiffert, M. Kluge, E. Teegen, D. Polenz, S. Lippert, D. Geisel, A. Reutzel-Selke, N. Raschzok, A. Andreou, J. Pratschke, I.M. Sauer, and B. Struecker.

Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct. Islets infused via the pancreatic duct leaked from the ductular system into the peri-ductular decellularized space despite their magnitude. TUNEL staining and Glucose stimulated insulin secretion revealed that islets were viable and functional after the process.
We present the first available protocol for perfusion decellularization of rat pancreata via three different perfusion routes. Furthermore, we provide first proof-of-concept for the repopulation of the decellularized rat pancreata with functional islets of Langerhans. The presented technique can serve as a bioengineering platform to generate implantable and functional endocrine Neo-Pancreata.