News

Functionalizable silica-based MPIO for cellular MRI

02.08.2013 In: Publications written by: Prof. Dr. Igor M. Sauer

Our latest manuscript entitled "Functionalizable silica-based micron-sized iron oxide particles for cellular Magnetic Resonance Imaging" was accepted for publication in the journal "Cell Transplantation".

Cellular therapies require methods for non-invasive visualization of transplanted cells. Micron-sized iron oxide particles (MPIOs) generate strong contrast in
Magnetic Resonance Imaging (MRI) and are therefore ideally suited as an intracellular contrast agent to image cells under clinical conditions. However,
MPIOs were previously not applicable for clinical use. Here, we present the development and evaluation of silica-based micron-sized iron oxide particles
(sMPIOs) with a functionalizable particle surface.

UPDATE: The paper is now available (Cell Transplant. 2013; 22(11): 1959-1570)

Tags: microparticles

12th Congress of the Cell Transplant Society

12.07.2013 In: Regenerative Medicine |Transplantation written by: Prof. Dr. Igor M. Sauer

The 12th Congress of the Cell Transplant Society tookplace in Milan, Italy, from July 7 to 11, 2013.
Nathanael Raschzok gave a presentation on "Loco-regional detection and stimulation of transplanted liver cells by particle-based miRNA depletion" and Martina Mogl on "isolation of adult hepatocytes and progenitor cells from explanted diseased human livers“.

Tags: Meeting

IEEE Engineering in Medicine and Biology Society

11.06.2013 In: Regenerative Medicine |Transplantation written by: Prof. Dr. Igor M. Sauer

The 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC’13) will take place 3-7 July 2013, at the Osaka International Convention Center, in Osaka, Japan.
The conference will cover diverse topics such as biomedical engineering, healthcare technologies, and medical and clinical applications.
The ESAO will be represented via a minisymposium entitled "Artificial Organs for Metabolic Support. The most Challenging Problems". Jan Wojcicki will give a presentation on "Artificial Organs for Metabolic Support: The Most Challenging Problems of Artificial Pancreas", Bernd Stegmayr on "Artificial Organs for Metabolic Support: The Most Challenging Problems in Severe Kidney Injury When Dialysis Is Necessary" and Igor Sauer on "Artificial Organs for Metabolic Support: The Most Challenging Problems of Liver Support".

Tags: Meetings

Noninvasive monitoring of liver cell transplantation

12.03.2013 In: Regenerative Medicine |Transplantation written by: Prof. Dr. Igor M. Sauer

Our latest review on „Noninvasive monitoring of liver cell transplantation“ (authors are N. Raschzok, H.M. Morgül, L. Stelter & I.M. Sauer) is available in Imaging in Medicine, 2013; 5: 47-61:
Liver cell transplantation was developed as a therapeutic alternative to solid liver transplantation in the management of liver-based metabolic disorders and may be useful for the treatment of acute or chronic liver failure. While clinical studies have demonstrated temporal amelioration of the symptoms of metabolic liver disorders by transplanted liver cells, the long-term outcome of liver cell transplantation is still insufficient. A major limitation for improving liver cell transplantation is the inability to track the fate of cells once they have been infused. Radionuclide-based imaging, MRI and optical methods have been investigated as methods for noninvasive monitoring of liver cell transplantation. This article summarizes and critically discusses these approaches, with a special focus on MRI-based tracking of transplanted liver cells and provides an outlook on possible clinical applications for the near future.

Tags: Publication

Einladunfgzur öffentlichen Abschlusspräsentation

01.03.2013 In: Regenerative Medicine |Transplantation written by: Prof. Dr. Igor M. Sauer

Sehr geehrte Damen und Herren,
Dear ladies and gentlemen,

Sie sind herzlich eingeladen, unserer öffentlichen Abschlusspräsentation unseres EU/EFRE-Projekts am 20.03.2013 um 15:00 Uhr beizuwohnen. Zusammen mit unseren Partnern der Firma microparticles GmbH werden wir den aktuellen Stand zur „Entwicklung von Partikel zur Detektion und ultralokoregionären Stimulation transplantierter Leberzellen“ darlegen.
You are cordially invited to attend our public presentation of our EU/EFRE project. Together with our partners of microparticles GmbH we will present our latest results concerning the „Development of particles for detection and ultralocoregional stimulation of transplanted liver cells“.

Wann/When?
20.03.2013 um/at 15:00

Wo/Where?
Experimentelle Chirurgie und Regenerative Medizin
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
Charité, Campus Virchow-Klinikum
Forschungshaus/BMFZ
Pilzraum, 1.OG

Wir wären dankbar, wenn Sie Ihr Kommen via email (anja.selke@charite.de)bestätigen könnten.
RSVP via email (anja.selke@charite.de).

Tags: Grant

Dr. Nils Bilecke

22.02.2013 In: Regenerative Medicine written by: Prof. Dr. Igor M. Sauer

Today, Nils Billecke successfully defended his doctoral thesis magna cum laude. The title of his presentation was „Bioreaktorsystem zur videomikroskopischen Langzeituntersuchung von Zellen in Mono- und Kokultur“.

Congratulations!

Tags: Thesis

GASL Poster Prize

16.01.2013 In: Regenerative Medicine written by: Prof. Dr. Igor M. Sauer

Nathanael Raschzok's poster entitled "Serum protein biomarkers for acute rejection
in liver transplantation" was awarded with the GASL 2013 poster prize during the 29th Annual Meeting of the German Association for the Study of the Liver (GASL) in Hannover, Germany. Co-authors are Kukuh A. Prabowo, Anja Reutzel-Selke, Rosa B. Schmuck, Mehmet H. Morgul, Laura M. Tannus, Stephanie König, Sven Jonas, Peter Neuhaus, and Igor M. Sauer.

Although 20–40% of patients experience at least one episode of acute rejection (AR) after liver transplantation (LTx), diagnosis of AR is still mainly based on tissue analysis from liver biopsies. Biomarker routinely taken from blood samples would be a powerful non-invasive tool for monitoring of the liver graft status. The aim of this study was to investigate the diagnostic and prognostic value of serum protein biomarkers for acute rejection in LTx recipients. Serum samples from n=20 patients with AR and n=15 stable controls were analyzed. CXCL9 and CD31 were up-regulated in AR samples compared to controls at the time point of histologically proven rejection and at earlier time points prior rejection. Areas under the Receiver Operation Characteristics (ROC) curves were 0.6 and 0.7 at the day of rejection and 0.8 at POD1 for CXCL9 and CD31, respectively. IL-6 was increased prior and during rejection, while CD44 showed an opposite trend.
Serum protein biomarkers could be valuable for detection and prediction of AR after LTx. However, a larger number of patients, additional control groups, and prospective clinical trials will be necessary to proof the clinical utility of this diagnostic tool.

Moreover, Rosa Schmuck presented her data on "Bile: miRNA pattern and cell morphology as a diagnostic tool after liver transplantation" (co-authors: Nathanael Raschzok, Anja Reutzel-Selke, Steffen Lippert, Stephanie König, Kukuh A. Prabowo, Mehmet H. Morgul, Laura M. Tannus, Sven Jonas, Peter Neuhaus, and Igor M. Sauer) and Luisa Lisboa her work on "MicroRNA miR-352 in early liver regeneration: what role?" (co-authors: Nathanael Raschzok, Annekatrin Leder, Natalie Schlüter, Marc Jörres, Susanne Kolano, Antje Butter, Steffen Lippert, Wiebke Werner, Peter Neuhaus, and Igor M. Sauer).

Tags: Award,Meeting

Neujahresessen

04.01.2013 In: Regenerative Medicine |Oncology |Transplantation |Digital Surgery written by: Prof. Dr. Igor M. Sauer

50 ways to love your liver

22.12.2012 written by: Prof. Dr. Igor M. Sauer

David Mücke successfully defended thesis

16.11.2012 In: Regenerative Medicine |Transplantation written by: Prof. Dr. Igor M. Sauer

Today, David Mücke successfully defended his thesis magna cum laude with respect to his work on the in vitro evaluation of MRI contrast agents for detection of primary human hepatocytes („In vitro Evaluierung von Magnetresonanztomografie-Kontrastmitteln für die Markierung primärer humaner Hepatozyten“).

Congratulations !

Tags: Thesis

XXXX ESAO Congress in Glasgow

11.11.2012 In: Regenerative Medicine |Transplantation written by: Prof. Dr. Igor M. Sauer

The European Society for Artificial Organs (ESAO) invites you to the XXXX ESAO Congress of the society to be held in Glasgow (Scotland, UK), September 11th-14th 2013.The motto of the ESAO congress will be 'lab to patient - from concept to treatment.

Tags: Meeting

Presentations at EASO 2012 in Rostock, Germany

29.09.2012 In: Regenerative Medicine |Transplantation written by: Prof. Dr. Igor M. Sauer

This year members of the team gave the following presentations:

“Liver: Current regenerative strategies and future solutions for the liver" (N. Raschzok, oral presentation)
"Neohybrid liver graft - a novel concept of in vivo tissue-engineering" (S. Rohn, oral presentation)
"Micro RNAs in liver regeneration: the mysterious MIR-352" (L. Lisboa, oral presentation)
"Micron-sized iron oxide particles for detection and loco-regional stimulation of transplanted liver cells" (A. Leder, oral presentation)
"Prospective validation of cross organ serum protein biomarkers – Initial results with CXCL9 and CD44 for diagnosis of acute liver rejection" (K.A. Prabowo, poster presentation)

Tags: Meeting,Lecture

MRI and ectopic liver cell transplantation - new paper

21.09.2012 In: Regenerative Medicine |Transplantation written by: Prof. Dr. Igor M. Sauer

Nathanael Raschzok’s latest paper on „Feasibility of fast dynamic MRI for noninvasive monitoring during ectopic liver cell transplantation to the spleen in a porcine model“ is now available in AJR Am J Roentgenol. 2012 Jun;198(6):1417-23.
Liver cell transplantation is a promising approach for the treatment of metabolic liver disorders. However, a method for noninvasive monitoring during liver cell transplantation is not available clinically. The aim of this study was to investigate the feasibility of fast dynamic MRI monitoring during liver cell infusion to the spleen, which is considered an ectopic implantation site for liver cell transplantation. Porcine liver cells were labeled with micron-sized iron oxide particles and infused to the spleens of pigs (n = 5) via the lineal artery. MRI was performed using a 3-T MR scanner. Initially, T1- and T2-weighted pulse sequences were tested. Thereafter, fast dynamic MRI was performed during cell infusion. MR findings were verified by immunohistological examinations.

Images from static MRI (TR/TE, 2500/105.2) showed significantly lower signal intensity and signal-to-noise ratio after cell infusion compared with pretransplant images. T2-weighted fast dynamic MRI enabled visualization of signal decrease of the spleen during cell infusion. When cells were infused systemically, no signal changes in the spleen were observed. This study shows that fast dynamic MRI can enable noninvasive monitoring during liver cell transplantation to the spleen. This approach could be useful for preclinical studies and for quality control of clinical liver cell transplantation.

Tags: Publication

R.B.V. Schmuck received Charité Robert-Koch-Prize 2012

21.09.2012 In: Oncology written by: Prof. Dr. Igor M. Sauer

Today, Rosa Schmuck received the 2012 Charité Robert-Koch-Prize for her doctoral thesis entitled „Genotypic and phenotypic characterization of side population of gastric cancer cell lines“ (group of Prof. C. Röcken).

The Side Population (SP) of tumor cell lines shares characteristics with tumor stem cells. In this study we phenotypically and genotypically characterized the SP of gastric cancer cell lines. SPs were obtained from MKN45- and AGS-gastric cancer cells using Hoechst 33342 staining and fluorescence-activated cell sorting (FACS). SP cells were subsequently studied morphologically (cytology, immunocytochemistry), on the transcriptional level (gene array) and in cell culture (recultivation assays). Genes differentially expressed in the SP cells were evaluated by immunohistochemistry in tissue from gastric cancer patients. SP cells were smaller and rounder then Non-SP cells. SP cells self-renewed in re-cultivation experiments and differentiated into SP- and Non-SP cells. Re-cultivated SP- and Non-SP cells showed distinct phenotypes in culture regarding cell shape and colony-formation. SP cells had increased levels of the stem cell markers CD133 and Musashi1. Transcriptional analyses demonstrated that SP cells express genes that encode for stem cell properties like FZD7, HEY1, SMO and ADAM17. Finally she found ADAM17 and FZD7 to be differentially expressed in human gastric cancer, with FZD7- positive intestinal type cancers showing a significant shorter patient survival. In conclusion human gastric cancer cell lines enclose a phenotypically and genotypically distinct cell population with tumor stem cell features. Phenotypical characteristics of this distinct cell population are also present in gastric cancer tissue and seem to correlate with patient survival.

Tags: Award,Thesis

TTS 2012 - Thank you!

01.08.2012 In: Transplantation written by: Prof. Dr. Igor M. Sauer

The Science Circuses are located at each end of the Exhibition Area. You will find the Mini-Theatres for the Mini-Oral Sessions here as well as the Poster Lounges and the Web Stations. Science Circus I includes Mini-Theatres 1 – 5; Science Circus II includes Mini-Theatres 6 – 10. In each Science Circus you will find Web Stations where you can access the web as well as the ePosters.
Via wireless headphones and dedicated channels for each mini-theater this is – to our knowledge – the first successful concept for mini-oral presentations!
Thanks to m-events and Interplan for the tremendous support!

Tags: Meeting

TTS 2012 | Over 500 presentations online!

29.07.2012 In: Transplantation written by: Prof. Dr. Igor M. Sauer

The LOC would like to thank all participants for a tremendous 24th International Congress of The Transplantation Society in Berlin!
2268 abstracts were submitted and more than 4800 delegates from 94 countries attended the congress!
The Postgraduate Weekend offered 14 workshops with 45 speakers. Beside 29 Sunrise Symposia with 103 Speakers, 34 State of the Art Sessions with 138 speakers and five Plenary Sessions (16 speakers) we had 53 sessions with 465 oral presentations and 37 sessions with 287 mini oral presentations !
Furthermore, we would like to thank Astrid Enke, Lena Dochat and Stefanie Rensch (Interplan) and the technical experts at m-Events for their excellent work !
As Science and Medicine is nothing without vivid life we would like to thank Rotfront, Berlin Comedian Harmonists and the Capital Dance Orchestra for their memorable performances!

All the great photos by Jan Pauls.
The organ sculptures were made by Jan Pareike.

Tags: Meeting

ESAO 2012 - Final Program Online!

28.07.2012 In: Regenerative Medicine |Transplantation written by: Prof. Dr. Igor M. Sauer

Prof. Dr. Gustav Steinhoff, congress president of the XXXIX. ESAO Congress, invites you to Rostock on September 26th – 29th, 2012. The venue of the ESAO 2012 congress is the Academy of Music and Theatre, which resides in an old monastery in the city centre.
The motto of the ESAO Congress 2012 will be “from replacement to regeneration – from science to clinic”. The current state of organ assist and organ support allows for a rapidly advancing clinical practice for several hundred thousand patients worldwide.
The scientific program committee did select 59 keynote lectures of renowned international experts, 131 selected oral presentations and 101 poster presentations from worldwide scientific contributors. Nine poster presentations were selected for short oral presentation. We provide a clear program structure by highlighting one special organ system each congress day: heart/cardiovascular (Chair: G. Steinhoff) , liver (Chair: S. Mitzner) and kidney (Chair: W. Ramlow). The program comprises 45 oral and 2 poster sessions with cardiovascular, dialysis, biomaterials and apheresis topics (www.esao2012.org). Above all the congress program integrates aspects of both basic science and clinical development with a clear focus on translation and clinical practice. We intend to host you on an excellent and exciting congress by inviting outstanding experts and by giving young and promising clinicians and scientists the opportunity to present their work. Especially for young scientists there will be one day for yESAO activities (Tuesday, Sept. 25, 2012). Industry symposia, a poster exhibition and an industrial exhibition will complete the congress program.

We are looking forward to seeing you in Rostock 2012.

Tags: Meeting

TTS 2012 | Presentations

27.07.2012 In: Transplantation written by: Prof. Dr. Igor M. Sauer

We had 4 oral presentations and one poster presentation at TTS 2012..
Martina Mogl presented "Neohybrid Liver Graft - a Novel Concept of in Vivo Tissue-Engineering"
Rosa Schmuck presented our first results concerning "miRNA Pattern Within the Bile as a Diagnostic Tool after Liver Transplantation"
Nathanael Raschzok gave an oral presentation entitled "Silica-Based Micron-Sized Iron Oxide Particles for Detection and Loco-Regional Stimulation of Transplanted Liver Cells"
Haluk Morgül gave a talk on "MicroRNA as Biomarker for Diagnosis and Prediction of Recurrence of Human Hepatocellular Carcinoma after Liver Transplantation - Preliminary Results from a Multicenter Database"
Furthermore, the group presented a poster concerning "Prospective Validation of Serum Protein Biomarkers for Detection of Acute Liver Rejection – Initial Results with CXCL9 and CD44"

Tags: Meeting

TTS Postgraduate Weekend

21.07.2012 In: Transplantation written by: Prof. Dr. Igor M. Sauer

The postgraduate program offers an up-to-date overview on pressing clinical and basic science topics with relevance for all participants of the Berlin 2012 meeting. The program is designed to provide clinicians with an overview of the most recent advances in basic research in a bench-to-bedside approach. Updates on immunosuppression, organ-specific processes, organ supply, immune monitoring and the relevance of animal models in transplantation will help both clinicians and researchers with basic information aligning their efforts and providing the best care of transplant patients in the years ahead.

Tags: Award

XXXIX ESAO Congress in Rostock, Germany

02.04.2012 In: Regenerative Medicine |Transplantation written by: Prof. Dr. Igor M. Sauer

On behalf of the European Society for Artificial Organs (ESAO), Prof. Dr. med. Gustav Steinhoff invites you to the XXXIX. ESAO Congress to be held in Rostock (Germany), September 26th – 29th, 2012. Rostock is a prospering and easy-to-reach hanseatic city directly located at the Baltic Sea coast. The venue of the ESAO 2012 congress is the Academy of Music and Theatre, which resides in an old monastery in the city centre. Rostock is home to one of the oldest universities in the world: founded in 1419. The motto of the ESAO Congress 2012 will be “from replacement to regeneration – from science to clinic”. The meeting will provide a clear program structure by highlighting one special organ system each congress day: heart/cardiovascular, liver and kidney. Above all the congress program integrates aspects of both basic science and clinical development with a clear focus on translation and clinical practice. We intend to prepare an excellent and exciting congress by inviting outstanding experts and by giving young and promising clinicians and scientists the opportunity to present their work. Especially for young scientists there will be one day for yESAO activities. Industry symposia, a poster exhibition and an industrial exhibition will complete the congress program.

Tags: Meeting

TTS 2012 Abstract submission now open!

01.10.2011 In: Transplantation written by: Prof. Dr. Igor M. Sauer

Please join the mailing list and follow us via Twitter @TTS2012 for latest information concerning the 24th International Congress of The Transplantation Society to be held in Berlin, Germany from July 15th - 19th 2012 !

Tags: Meeting

CARS microscopy of MPIO

10.09.2011 In: Transplantation |Regenerative Medicine written by: Prof. Dr. Igor M. Sauer

Following a successful project sponsored by the BMBF G. Pless, I.M. Sauer and U. Rauen report on the "Improvement of the cold storage of isolated human hepatocytes" (Cell Transplant. 2011 Jun 7. [Epub ahead of print]).
Increasing amounts of human hepatocytes are needed for clinical applications and different fields of research, such as cell transplantation, bioartificial liver support and pharmacological testing. This demand calls for adequate storage options for isolated human liver cells. As cryopreservation results in severe cryoinjury, short term storage is currently performed at 2-8º C in preservation solutions developed for the storage of solid organs. However, besides slowing down cell metabolism, cold also induces cell injury, which is, in many cell types, iron-dependent and not counteracted by current storage solutions. In this study, we aimed to characterize storage injury to human hepatocytes and develop a customized solution for cold storage of these cells. Human hepatocytes were isolated from material obtained from partial liver resections, seeded in monolayer cultures and, after a pre-culture period, stored in the cold in classical and new solutions followed by rewarming in cell culture medium.Human hepatocytes displayed cold-induced injury, resulting in > 80% cell death (LDH release) after one week of cold storage in University of Wisconsin solution or cell culture medium and 3 h of rewarming. Cold-induced injury could be significantly reduced by the addition of the iron chelators deferoxamine and LK 614. Experiments with modified solutions based on the new organ preservation solution Custodiol-N showed that ion-rich variants were better than ion-poor variants, chloride-rich solutions better than chloride-poor solutions, potassium as main cation superior to sodium and pH 7.0 superior to pH 7.4. LDH release after two weeks of cold storage in the thus optimized solution was below 20%, greatly improving cold storage of human hepatocytes. The results were confirmed by the assessment of hepatocellular mitochondrial membrane potential and functional parameters (resazurin reduction, glucacon-stimulated glucose liberation) and thus suggest the use of a customized hepatocyte storage solution for the cold storage of these cells.

Tags: Publication

TTS 2012: Follow us via Twitter!

03.09.2011 In: Transplantation written by: Prof. Dr. Igor M. Sauer

The 24th International Congress of The Transplantation Society to be held in Berlin, Germany from July 15th - 19th 2012 is designed for physicians, surgeons, scientists and organ procurement personnel, who are interested in clinical and research aspects of solid organ, cell and tissue transplantation. The program is developed to encourage the exchange of new scientific and clinical information, and support an interchange of opinions regarding care and management issues, as well as socioeconomic, ethical and regulatory issues relevant to transplantation.
In addition to the classical types of scientific sessions including plenary sessions, symposia, workshops and poster presentations, we will also offer new types of scientific sessions within the Forum Futurum.
The Forum Futurum is a forum integrated in the congress that will take place on three days. Each day is assigned to a topic and the forum is dedicated to cutting-edge science in our field. The topics are Regenerative Medicine, Imaging and Tailored Pharmacotherapy.
The Forum Futurum is designed to be a highly interactive communication space where companies can introduce their products and conversations about the latest research are stirred. In a futuristic environment the Forum Futurum contributes to an extraordinary TTS 2012 Exhibition experience and will provide exhibitors the opportunity to highlight new product information to physicians and health care professionals. Enhance the educational element of your company's noteworthy products and services with a presentation in the Forum Futurum. The Forum Futurum provides exhibitors with a unique and effective marketing opportunity to hold live promotional presentations or activities designed to raise awareness of featured services and products.
The Forum Futurum will make its debut in the TTS 2012 Exhibit Hall, featuring experts from companies and scientific groups providing state-of-the-art content-led information about new technologies, products and ideas. The Forum Futurum will be open July 16th – July 18th. Every day is dedicated to one emerging field in transplantation:
Monday, July 16th, 2012: One Day on Regenerative Medicine
Tuesday, July 17th, 2012: One Day on Imaging
Wednesday, July 18th, 2012: One Day on Tailored Pharmacotherapy

Tags: Meeting

Fast dynamic MRI during liver cell Tx

01.09.2011 In: Transplantation |Regenerative Medicine written by: Prof. Dr. Igor M. Sauer

Micrometer-sized iron oxide particles (MPIOs) attract increasing interest as contrast agents for cellular tracking by clinical Magnetic Resonance Imaging (MRI). Despite the great potential of MPIOs for in vivo imaging of labeled cells, little is known on the intracellular localization of these particles following uptake due to the lack of techniques with the ability to monitor the particle uptake in vivo at single-cell level. Here, we show that coherent anti-Stokes Raman scattering (CARS) microscopy enables non-invasive, label-free imaging of MPIOs in living cells with sub-micron resolution in three dimensions. CARS allows simultaneous visualization of the cell framework and the MPIOs, where the particles can be readily distinguished from other cellular components of comparable dimensions, and localized inside the cell.
The fruitful cooperation with the FOM Institute AMOLF in Masterdam resulted in the paper "CARS microscopy for the visualization of micrometer-sized iron oxide MRI contrast agents in living cells" (Rago G, Langer CM, Brackman C, Day JP, Domke KF, Raschzok N, Schmidt C, Sauer IM, Enejder A, Mogl MT, Bonn M.) published in Biomed Opt Express. 2011 Sep 1;2(9):2470-83.

Tags: Publication

Improved cold storage of human hepatocytes

31.08.2011 In: Transplantation |Regenerative Medicine |Oncology written by: Prof. Dr. Igor M. Sauer

As a first result of our latest projects concerning the role of miRNA in liver regeneration the American Journal of Physiology - Regulatory, Integrative and Comparative Physiology has accepted our paper "Temporal expression profiles indicate a primary function for microRNA during the peak of DNA replication after rat partial hepatectomy": The liver has the unique capacity to regenerate after surgical resection. However, the regulation of liver regeneration is not completely understood. Recent reports indicate an essential role for small non-coding microRNAs (miRNAs) in the regulation of hepatic development, carcinogenesis, and early regeneration. We hypothesized that miRNAs are critically involved in all phases of liver regeneration after partial hepatectomy. We performed miRNA microarray analyses after 70% partial hepatectomy in rats under isoflurane anesthesia at different time points (0 hours - 5 days) and after sham laparotomy. Putative targets of differentially expressed miRNAs were determined using a bioinformatic approach. 2D-PAGE proteomic analyses and protein identification were performed on specimens at 0 and 24 hours after resection. The temporal dynamics of liver regeneration were characterized by BrdU, PCNA, IL-6, and HGF. We demonstrate that miRNA expression patterns changed during liver regeneration and that these changes were most evident during the peak of DNA replication at 24 hours after resection. Expression of thirteen miRNAs was significantly reduced 12-48 hours after resection (> 25% change), ouf of which downreguation was confirmed in isolated hepatocytes for 6 miRNAs at 24 hours, whereas three miRNAs were significantly upregulated. Proteomic analysis revealed 65 upregulated proteins; among them 23 represent putative targets of the differentially expressed miRNAs. We provide a temporal miRNA expression and proteomic dataset of the regenerating rat liver, which indicates a primary function for miRNA during the peak of DNA replication. These data will assist further functional studies on the role of miRNAs during liver regeneration. Authors are N. Raschzok, W. Werner, H. Sallmon, N. Billecke, C. Dame, P. Neuhaus and I.M. Sauer.

Tags: Publication

Year