Einstein Center Digital Future – Opening
In: Meetings written by: Prof. Dr. Igor M. Sauer
Einstein Visiting Fellow Prof. Stefan G. Tullius
In: General written by: Prof. Dr. Igor M. Sauer
Prof. Dr. Stefan G. Tullius, Harvard Medical School, became Einstein BIH Visiting Fellow at the Charité, Department of Surgery.
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:
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.
To establish a clinical bio-repository as a pre-requisite for a clinical research VCA program.
To implement a clinical VCA research program (hand, abdominal wall, uterus) as a multi- disciplinary and translational effort.
Tags: VCA,Uterus Transplantation,Hand Transplantation,Composite Tissue Transplantation
Transplantation in Transition
In: Meetings written by: Prof. Dr. Igor M. Sauer
Foschungs-Colloquium 2017 - Impressions
In: Meetings |Presentations written by: Prof. Dr. Igor M. Sauer
Engineering an endocrine Neo-Pancreas
In: Publications written by: Prof. Dr. Igor M. Sauer
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.
Tags: Decellularization,Rezellularization,NeoPancreas,Islet Cells,Pancreas
Recellularization of rat livers: morphology and function
In: Publications written by: Prof. Dr. Igor M. Sauer
Decellularization of livers is a well-established procedure. Data on different reseeding techniques or the functional evolution and re-organization processes of repopulated grafts remains limited.
We established a proprietary, customized bioreactor to repopulate decellularized rat livers (n=21) with primary rat hepatocytes (150 x 106 cells) via the hepatic artery and to subsequently evaluate graft morphology and function during seven days of ex vivo perfusion. Grafts were analyzed at 1h, 6h, 12h, 24h, 3d, 5d and 7d after recellularization (all n=3) by immunohistologic evaluation, hepatocyte-related enzyme (AST, ALT, LDH) and albumin measurement in the perfusate.
To the best of our knowledge, this is the first available protocol for repopulation of rat livers via the hepatic artery. Within the first 24 hours after repopulation, the hepatocytes seemed to migrate out of the vascular network and form clusters in the parenchymal space around the vessels. Graft function increased for the first 24 hours after repopulation with a significantly higher function compared to standard 2D culture after 24 hours. Thereafter, graft function constantly decreased with significantly lower values after six and seven days of perfusion, although histologically viable hepatocytes were found even after this period. Our data suggests that due to a constant loss of function, repopulated grafts should potentially be implanted as soon as cell engraftment and graft re-organization are completed.
Authors are Antje Butter, Khalid Aliyev, Karl-Herbert Hillebrandt, Nathanael Raschzok, Martin Kluge, Nicolai Seiffert, Peter Tang, Hendrik Napierala, Muhammad Imtiaz Ashraf, Anja Reutzel-Selke, Andreas Andreou, Johann Pratschke, Igor Maximilian Sauer, and Benjamin Struecker.
Tags: Decellularization,Rezellularization,Liver,Transplantation
Vascular anatomy of the juvenile Göttingen minipig
In: Publications written by: Prof. Dr. Igor M. Sauer
Over the past 50 years, image-guided procedures have been established for a wide range of applications. The development and clinical translation of new treatment regimens necessitate the availability of suitable animal models. The juvenile Göttingen minipig presents a favourable profile as a model for human infants. However, no information can be found regarding the vascular system of juvenile minipigs in the literature. Such information is imperative for planning the accessibility of target structures by catheterization.
We present here a complete mapping of the arterial system of the juvenile minipig based on contrast-enhanced computed tomography. Four female animals weighing 6.13 ± 0.72 kg were used for the analyses. Imaging was performed under anaesthesia, and the measurement of the vascular structures was performed independently by four investigators. Our dataset forms a basis for future interventional studies in juvenile minipigs, and enables planning and refinement of future experiments according to the 3R (replacement, reduction and refinement) principles of animal research.
Authors are J. Siefert, K.H. Hillebrandt, M. Kluge, D. Geisel, P. Podrabsky, T. Denecke, M. Nösser, J. Gassner, A. Reutzel-Selke, B. Strücker, M.H. Morgul, S. Guel-Klein, J.K. Unger, A. Reske, J. Pratschke, I.M. Sauer, and N. Raschzok.
Monitoring of hepatocyte transplantation by MRI
In: Publications written by: Prof. Dr. Igor M. Sauer
This volume features up-to-date protocols for the isolation, preservation, and validation of various cell sources comprising large and small animal models, examining the impact of cell transplantation on acute and chronic liver diseases. Hepatocyte Transplantation: Methods and Protocols guides readers through laboratory protocols for the generation of humanized livers for the assessment of biological actions in vivo and techniques to monitor cell engraftment after cell transplantation in vivo are described and procedures for computational analyses of hepatocyte transplantation.
Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Hepatocyte Transplantation: Methods and Protocols is an essential resource for researchers and clinicians to assess the biological as well as the therapeutic potential of hepatocyte transplantation.
Tags: Cell Transplantation,MRI,Particles
Staatsexamen
In: General written by: Prof. Dr. Igor M. Sauer
More than 100 days of loops of learning and 3 days conquering more than 300 questions: 5 faces. Congratulations! We are all looking forward to having you back in the lab!
HCC: miRNA profiles of the tumor-surrounding tissue
In: Publications written by: Prof. Dr. Igor M. Sauer
The HCC patients were significantly older than the patients with cirrhosis only (B: 60.6 and A: 49.9, p<0.001) and showed higher levels of ALT (A: 0.76μkat/l, B: 1.02μkat/, p=0.006) and AFP (A: 5.8ng/ml, B: 70.3ng/ml, p<0.001), whereas the bilirubin levels were higher in the cirrhosis only group (p=0.002). Using age (cut-off 50.23years) and AFP (cut-off 4.2ng/ml) thresholds, the levels of expression of miR-1285-3p and miR-943 differentiated between the patients with HCC and cirrhosis from those with cirrhosis only with an accuracy of 96.3%. This is the first report about the use of stepwise penalized logistic regression and decision tree analyses of miRNA expressions in the tumor-surrounding tissue combined with clinical parameters for the diagnosis of HCC.
Authors are Mehmet Haluk Morgul, Sergej Klunk, Zografia Anastasiadou, Ulrich Gauger, Corinna Dietel, Anja Reutzel-Selke, Philipp Felgendref, Hans-Michael Hau, Hans-Michael Tautenhahn, Rosa Bianca Schmuck, Nathanael Raschzok, Igor Maximillian Sauer, and Michael Bartels. Exp Mol Pathol. 2016 Aug 20;101(2):165-171. doi: 10.1016/j.yexmp.2016.07.014. [Epub ahead of print]
Tags: miRNA
Bile: miRNA Pattern post OLT
In: Publications written by: Prof. Dr. Igor M. Sauer
Bile rather than blood depicts the local inflammation in the liver and may improve prediction and diagnosis of acute cellular rejection (ACR) after liver transplantation (OLT). Secretome and miRNAs were analyzed during the first two weeks and on clinical suspicion of ACR in the bile of 45 OLT recipients. Levels of CD44, CXCL9, miR-122, miR-133a, miR-148a and miR-194 were significantly higher in bile of patients who developed ACR within the first 6 months after OLT and during ACR. Analysis of secretome and miRNA in bile could further our understanding of the local inflammatory process during rejection.
Hepatocyte isolation after laparoscopic liver resection
In: Publications written by: Prof. Dr. Igor M. Sauer
Liver tissue obtained from partial hepatectomy is a common source for isolation of primary human hepatocytes. Until now, liver resections were most commonly performed by conventional open surgery. Although the laparoscopic approach is currently emerging in liver surgery, data on the outcome of hepatocyte isolation from laparoscopically resected liver tissue is not available. A total of 22 hepatocyte isolations were performed using the two-step collagenase perfusion technique from October 2015 until March 2016. Liver tissue was obtained from n=15 open liver resections (OLR) and n=7 laparoscopic liver resections (LLR). Isolation parameters (cell yield, viability, percoll survival) were assessed and hepatocyte function (plating efficiency, urea, albumin, and aspartate aminotransferase) was measured over a culture period of 6 days (OLR: n=13; LLR: n=3). Total cell yield (OLR: 36.81 ± 6.77 x106 cells/g vs. LLR 16.84 ± 10.66 x106 cells/g, p=0.0318) as well as viable yield (OLR 31.70 ± 6.05 x106 cells/g vs. LLL 14.70 ± 9.89 x106 cells/g, p=0.0260) were significantly higher in the OLR group. Subgroup analysis revealed that the worse outcome of isolation of laparoscopically resected liver tissue was associated with right-lateral laparoscopic liver resections, while hepatocyte isolation from left-lateral laparoscopic liver resections was as effective as from open surgery. Hepatocyte function did not differ between hepatocytes from openly resected versus left-lateral laparoscopically resected liver tissue. We here present the first data on hepatocyte isolation from laparoscopic liver surgery. While the overall outcome is worse compared to open surgery, our data suggest that liver tissue from laparoscopic resection of the left lobe is an excellent source for primary human hepatocytes.
Tags: Hepatocyte Isolation,Liver
BIH Charité Clinician Scientist Symposium
In: Meetings written by: Prof. Dr. Igor M. Sauer
SPARK Berlin supports Fikatas Knot
In: Projects |Grant |Surgical Techniques written by: Prof. Dr. Igor M. Sauer
We are very pleased to announce that Dr. Panagiotis Fikatas' project “Device for ready-prepared surgical knots” was selected for both, funding and mentorship.
SPARK was created to overcome the hurdles associated with translating academic discoveries into therapeutics and diagnostics that address unmet medical needs. The SPARK mission is to help academics overcome the obstacles involved in moving their early discoveries from bench to bedside, to educate faculty, postdoctoral fellows and graduate students on the translational research process and path to clinical application, so that development of promising discoveries becomes second nature to our institution, and to develop more cost-effective and innovative approaches to drug development .
Congratulations!
Tags: Surgical Techniques
Ethicon Zukunfts-Award 2016
In: Award written by: Prof. Dr. Igor M. Sauer
International Medical Tournament 2016
In: Award written by: Prof. Dr. Igor M. Sauer
Congratulations!
The International Medical Tournament is a team competition for future doctors, which provides unique professional experience such as solving complex diagnostic cases from real clinical practice without any risks, presentation and discussion of solutions among students and experts. The main goal of the competition is to help medical students gather and develop lacking skills for future medical practice, critical thinking in diagnostic process, abilities of teamwork, presentation and rhetorical skills.
NeoHybrid liver graft – proof of concept
In: Publications written by: Prof. Dr. Igor M. Sauer
Authors are Susanne Rohn, Jan Schroeder, Henriette Riedel, Dietrich Polenz, Katarina Stanko, Anja Reutzel-Selke, Peter Tang, Lydia Brusendorf, Nathanael Raschzok, Peter Neuhaus, Johann Pratschke, Birgit Sawitzki, Igor M. Sauer, and Martina T. Mogl.
Aim of the project was the evaluation of a new concept for in vivo tissue engineering using autologous primary human hepatocytes and hepatic progenitor cells isolated from diseased livers explanted during orthotopic liver transplantation (LTx). Cells will be isolated and infused into the spleen for repopulation of the allogeneic liver graft. The latter is serving as biological matrix for the engraftment of autologous cells. Once these cells have engrafted, it is assumed that autologous cells will repopulate the allogeneic liver, since they should have a selective advantage due to their autologous origin. It is postulated that this will lead to a neo-hybrid liver graft, reducing immunogenicity and inducing immunoregulation thus minimizing the need for extensive immunosuppression and eventually inducing operational tolerance.
We therefore developed a new rat model for combined liver and liver cell transplantation under stable immunosuppression. Immunohistochemistry demonstrated the engraftment of transplanted cells, as confirmed by fluorescence in-situ hybridization, showing repopulation of the liver graft with 15.6 % male cells (± 1.8 SEM) at day 90. The quantitative PCR revealed 14.15 % (mean ± 5.09 SEM) male DNA at day 90. Engraftment of transplanted autologous cells after combined liver and cell transplantation was achieved for up to 90 days under immunosuppression. Immunohistochemistry indicated cell proliferation, and the fluorescence in-situ hybridization results were partly confirmed by quantitative RT-PCR. This new protocol in rats appears feasible to address long-term function and eventually induction of operational tolerance in the future.
Tags: NeoHybrid Liver Graft,Cell Transplantation,Cell Culture,Cell Isolation,Liver Transplantation
LTx – microRNA signatures in peripheral blood ?
In: Publications written by: Prof. Dr. Igor M. Sauer
We investigated whether microRNA signatures in whole blood samples are associated with acute cellular rejection (ACR) after liver transplantation. Blood samples were collected using Paxgene technology and analyzed by microarrays and qRT-PCR. microRNA signatures failed to distinguish between 19 patients with ACR and 16 controls. Let-7b-5p and let-7c were up-regulated in a subgroup of patients with ACR during the 6th and 7th postoperative day but failed in an independent validation of 20 patients. microRNA signatures in whole blood processed by Paxgene technology are not suited for detection of ACR after liver transplantation.
Tags: miRNA,Liver Transplantation,Liver
Single Pass Albumin Dialysis – Dose finding study
In: Publications written by: Prof. Dr. Igor M. Sauer
Aim of these studies was to define the optimal conditions for SPAD in a standardized experimental set-up. Albumin concentration was adjusted to either 1%, 2%, 3%, or 4%, while the flow rate of the dialysate was kept constant at a speed of 700 ml/h. The flow rate of the dialysate was altered between 350, 500, 700, and 1000 ml/h, whereas the albumin concentration was continuously kept at 3%.
This study revealed that the detoxification of albumin bound substances could be improved by increasing the concentration of albumin in the dialysate with an optimum at 3%. A further increase of the albumin concentration to 4% did not lead to a significant increase in detoxification. Furthermore, we observed a gradual increase of the detoxification efficiency for albumin bound substances, from 350 ml/h to 700 ml/h (for bilirubin) or 1000 ml/h (for bile acids) of dialysate flow. Water-soluble toxins (ammonia, creatinine, urea, uric acid) were removed almost completely, regardless of albumin concentration or flow rate.
Tags: Albumin Dialysis,Liver Support Therapy,Artificial Liver
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In: Projects |Other written by: Prof. Dr. Igor M. Sauer
Although we do hate Facebook, feel kind of robbed and dislike the music – We have to admit: 7,201,027 clicks (as of January 25th, 2016) are impressive…
Feature in Berliner Zeitung on Tissue Engineering
In: Press written by: Prof. Dr. Igor M. Sauer
ESOT | YPT – Interview with Karl Hillebrandt
In: Award written by: Prof. Dr. Igor M. Sauer
His abstract "Optimized decellularization of rat livers byarterial and portal venous perfusion underoscillating pressure conditions" and the accompanying video were the most voted at the Rising Stars Session, where the audience voted live for the best video abstract. You can read Karl's abstract in the special ESOT2015 issue of Transplant International.
Tags: Liver,Recellularization,Decellularization,Regeneration
Evaluation of a new knotting concept – Fikatas knot
In: Projects written by: Prof. Dr. Igor M. Sauer
Implantation of a Neo Bile Duct in domestic pigs
In: Publications written by: Prof. Dr. Igor M. Sauer
Extrahepatic bile duct injuries remain severe complications during cholecystectomy and often require reconstruction by bilioenteric anastomosis (i.e. hepatico-jejunostomy), which comes along with further long-term complications (e.g. recurring ascending cholangitis, secondary biliary cirrhosis). Furthermore, in case of inherent extrahepatic biliary atresia or during liver transplant artificial or engineered bile ducts could enable novel surgical strategies without the need for hepatico-jejunostomy. We present data on the implantation of in vitro generated Neo Bile Ducts in five domestic pigs. Neo Bile Ducts were engineered through decellularization of allogeneic blood vessels and recellularization with autologous cholangiocytes.On postoperative days 0, 1, 7 and 14 blood samples were taken and analyzed (AST, ALT, Bilirubin, Alkaline Phosphatase, Creatinine and Leukocytes). An magnetic resonance cholangiography was performed on postoperative day 14 with one pig. 14 days after implantation pigs were sacrificed and bile ducts were explanted. All pigs survived the complete study period without severe complications. None of the pigs showed signs of biliary leakage or peritonitis. Neo Bile Ducts were infiltrated by neutrophils and neo-angiogenesis was observed around and into the implanted tissue. Whether the presented technique enables the long-term replacement of native bile ducts has to be further evaluated.
Tags: Bile Ducts,Recellularization,Decellularization,Regeneration,Tissue Engineering
Human hepatocyte isolation – new paper
In: Publications written by: Prof. Dr. Igor M. Sauer
Primary human hepatocytes are widely used for basic research, pharmaceutical testing, and therapeutic concepts in regenerative medicine. Human hepatocytes can be isolated from resected liver tissue. Preoperative portal vein embolization (PVE) is increasingly used to decrease the risk of delayed postoperative liver regeneration by induction of selective hypertrophy of the future remnant liver tissue. The aim of this study was to investigate the effect of PVE on the outcome of hepatocyte isolation. Primary human hepatocytes were isolated from liver tissue obtained from partial hepatectomies (n=190) using the two-step collagenase perfusion technique followed by Percoll purification. Of these hepatectomies, 27 isolations (14.2%) were performed using liver tissue obtained from patients undergoing PVE prior to surgery. All isolations were characterized using parameters that had been described in the literature as relevant for the outcome of hepatocyte isolation. The PVE and non-PVE groups were similar in regard to donor parameters (sex, age, indication for surgery), isolation parameters (liver weight, cold ischemic time), and the quality of the liver tissue. The mean initial viable cell yield did not differ between the PVE and non-PVE groups (10.16±2.03x106 cells/g vs. 9.70±0.73 x106 cells/g, p=0.499). The initial viability was slightly better in the PVE-group (77.8 ±2.03% vs. 74.4 ±1.06%). The mean viable cell yield (p=0.819) and the mean viability (p=0.141) after Percoll purification did not differ between the groups. PVE had no effect on enzyme leakage and metabolic activity of cultured hepatocytes. Although PVE leads to drastic metabolic alterations and changes in hepatic blood flow, embolized liver tissue is a suitable source for the isolation of primary human hepatocytes and is equivalent to untreated liver tissue in regard to cell yield and viability.
Tags: Cell Culture,Cell Isolation,Cell Transplantation,Liver
Dr. Jan Schröder
In: Thesis written by: Prof. Dr. Igor M. Sauer
Karl Hillebrandt – YPT Rising Star
In: Award written by: Prof. Dr. Igor M. Sauer
Karl Hillebrandt won this year's YPT Rising Stars Video Session Award. He presented the studies on „Optimized decellularization of rat livers by arterial and portal venous perfusion under oscillating pressure conditions“ during the 17th congress of the European Society for Organ Transplantation (ESOT) 2015 in Brüssel. Young Professionals in Transplantation (YPT) is a forum for junior professionals throughout Europe working in the field of transplantation.
Tags: Liver,Recellularization,Decellularization,Regeneration
The Morning After
In: Publications written by: Prof. Dr. Igor M. Sauer
They conclude, „that our study urges us to study the immune system response in liver allograft recipients during the very early phases after liver transplantation and to explore how events in immune organs and the allograft are reflected within the serum. Whether the patterns observed truly represent early detection of ACR versus tolerance, or a combination of both, requires further study and experimentation, including the identification of the cellular sources of these and other potential markers of immune outcome. It seems that despite significant levels of immunosuppressive drugs, immune activation and engagement occurs very early after human liver transplant, within the first 24 hours, in a manner that may have similarities with experimental animal models. Thus, the morning after effect could be an exciting window to longer-term immune outcomes, rather than just being preoccupied with observing important routine outcomes and detecting early complications.“
Tags: Liver,Biomarkers,LTx
Publication in Jove
In: Publications written by: Prof. Dr. Igor M. Sauer
Authors are K. Hillebrandt, D. Polenz, A. Butter, P. Tang, A. Reutzel-Selke, A. Andreou, H. Napierala, N. Raschzok, J. Pratschke, I.M. Sauer, and B. Struecker . The presented techniques for liver harvesting, cannulation and perfusion using our proprietary device enable sophisticated perfusion set-ups to improve decellularization and recellularization experiments in rat livers.
Tags: Decellularisation,Liver
microRNAs in liver tissue engineering
In: Publications written by: Prof. Dr. Igor M. Sauer
miRNA-based technologies provide attractive tools for several liver tissue engineering approaches. Herein, we review the current state of miRNA applications in liver tissue engineering. Several miRNAs have been implicated in hepatic disease and proper hepatocyte function. However, the clinical translation of these findings into tissue engineering has just begun. miRNAs have been successfully used to induce proliferation of mature hepatocytes and improve the differentiation of hepatic precursor cells. Nonetheless, miRNA-based approaches beyond cell generation have not yet entered preclinical or clinical investigations. Moreover, miRNA-based concepts for the biliary tree have yet to be developed. Further research on miRNA based modifications, however, holds the promise of enabling significant improvements to liver tissue engineering approaches due to their ability to regulate and fine-tune all biological processes relevant to hepatic tissue engineering, such as proliferation, differentiation, growth, and cell function.
Tags: miRNA,Tissue Engineering,Decellularization,Recellularization,Cell Transplantation
CD44 and CXCL9 predicting rejection after LTx
In: Publications written by: Prof. Dr. Igor M. Sauer
Authors are Nathanael Raschzok, Anja Reutzel-Selke, Rosa Bianca Schmuck, Mehmet Haluk Morgul, Ulrich Gauger, Kukuh Aji Prabowo, Laura-Marie Tannus, Annekatrin Leder, Benjamin Struecker, Sabine Boas-Knoop, Michael Bartels, Sven Jonas, Christian Lojewski, Gero Puhl, Daniel Seehofer, Marcus Bahra, Andreas Pascher, Johann Pratschke, and Igor Maximilian Sauer.
The diagnosis of acute cellular rejection (ACR) after liver transplantation is based on histological analysis of biopsies because non-invasive biomarkers for allograft rejection are not yet established for clinical routines. CD31, CD44, and CXCL9 have previously been described as biomarkers for cross-organ allograft rejection. Here, we assessed the predictive and diagnostic value of these proteins as serum biomarkers for clinically significant ACR in the first six months after liver transplantation in a prospective study. The protein levels were measured in 94 patients immediately prior to transplantation, at postoperative days (POD) 1, 3, 7, and 14, and when biopsies were performed during episodes of biochemical graft dysfunction. Our results suggest that CD44 and CXCL9 may serve as predictive biomarkers to identify liver allograft recipients at risk for clinically significant ACR.
Cover – march issue of Tissue Engineering
In: Publications written by: Prof. Dr. Igor M. Sauer
One of the figures of our paper „Porcine liver decellularization under oscillating pressure conditions – A technical refinement to improve the homogeneity of the decellularization process“ made it to the cover of the march issue of Tissue Engineering, Part C : Methods.
Congratulations to Dietrich Polenz, who made the corrosion cast of a decellularized pig liver matrix: red, hepatic artery; blue, portal vein; yellow, bile duct and gallbladder.
Particles for microRNA-targeted manipulation
In: Publications written by: Prof. Dr. Igor M. Sauer
Particle-based delivery systems for therapeutic manipulation and tracking of transplanted cells by magnetic resonance imaging (MRI) are commonly based on nanometer-sized superparamagnetic iron oxide particles (SPIOs). Here, we present a proof of concept for multifunctional, silica based micron-sized iron oxide-containing particles (sMPIO) that combine fluorescence imaging, MRI tracking, and on-the-spot targeting of specific microRNAs on a particle surface for therapeutic manipulation by RNA interference. Antisense locked nucle-LNA) were covalently bound to the surface of silica-based, DAPI-integrated, micron-sized iron oxide particles (sMPIO--LNA). In vitro studies using primary human hepatocytes showed rapid particle uptake (4 hours) that was accompanied by significant depletion of the targeted microRNA Let7g (80%), up- regulation of the target proteins Cyclin D1 and c-Myc, and specific proteome changes. sMPIO--LNA- labeled cells were successfully detected by fluorescence imaging and could be visualized by MRI after intrasplenic transplantation in rats. This new theranostic particle provides a promising tool for cell transplantation where cellular imaging and microRNA-based manipulation is needed.
Biomaterials is the leading journal in its field. Impact factors released by ISI in July 2014 showed Biomaterials with an impact factor of 8.312!
Tags: Particles
Decellularization of pancreata – EPITA Award
In: Meetings |Award written by: Prof. Dr. Igor M. Sauer
Ben Strücker presented three effective protocols for rat pancreas perfusion decellularization, evaluating different perfusion routes. In contrast to liver decellularization the perfusion route seems to have no major impact on decellularization results. The dPECMs could serve for cellular repopulation with islets from a different (xenogene) origin to generate functional, transplantable endocrine pancreata in vitro.
Tags: Decellulariztaion,Pancreas
Rebeka Major: BIH Promotionsstipendium
In: Grant |General written by: Prof. Dr. Igor M. Sauer
In the Berlin Institute of Health (BIH), the Max Delbrück Center for Molecular Medicine (MDC) and the Charité - Universitätsmedizin Berlin have joined forces. The core idea is to combine translational research with an overarching systems medicine approach to bridge the gap between basic research and clinical application.
Tags: INDY,Liver,Regeneration
Presentations at DTG 2014
In: Meetings written by: Prof. Dr. Igor M. Sauer
Tags: DTG,Decellularization,miRNA
Ben Strücker: Charité Clinical Scientist
In: Meetings written by: Prof. Dr. Igor M. Sauer
His project is entitled „Humanized Porcine Liver““. Clinical mentor is Prof. Dr. Johann Pratschke, scientific mentors is Priv.-Doz. Dr. med Igor M. Sauer.
The program is supported by Stiftung Charité which was endowed by the entrepreneur Johanna Quandt in order to promote biomedical "knowledge entrepreneurs" that is, change makers in biomedicine at the Charité. The goal of this program is to develop new career paths in clinical specialist medical training. The focus of the training program "Clinical Scientist" is translational research ("bench-to-bedside") which will be realized by a reduction in clinical routine and an improved curriculum with defined goals.
Tags: Recellularization,Decellularization,Liver,Liver Support Therapy
Sham Laparotomy and microRNA Expression in Rats
In: Publications written by: Prof. Dr. Igor M. Sauer
Studies on liver regeneration following partial hepatectomy (PH) have identified several microRNAs (miRNAs) that show a regulated expression pattern. These studies involve major surgery to access the liver, which is known to have intrinsic effects on hepatic gene expression and may also affect miRNA screening results. We performed two-third PH or sham laparotomy (SL) in Wistar rats to investigate the effect of both procedures on miRNA expression in liver tissue and corresponding plasma samples by microarray and qRT-PCR analyses. As control groups, non-treated rats and rats undergoing anesthesia only were used. We found that 49 out of 323 miRNAs (15%) were significantly deregulated after PH in liver tissue 12 to 48 hours postoperatively (>20% change), while 45 miRNAs (14%) were deregulated following SL. Out of these miRNAs, 10 miRNAs were similarly deregulated after PH and SL, while one miRNA showed opposite regulation. In plasma, miRNA upregulation was observed for miR-133a and miR-133b following PH and SL, whereas miR-100 and miR-466c were similarly down-regulated following anesthesia and surgery. We show that miRNAs are indeed regulated by sham laparotomy and anesthesia in rats. These findings illustrate the critical need for finding appropriate control groups in experimental surgery.
Authors are W. Werner, H. Sallmon, A. Leder, S. Lippert, A. Reutzel-Selke, M.H. Morgül, S. Jonas, S. Dame, P. Neuhaus, J. Iacomini, S.G. Tullius, I.M. Sauer and N. Raschzok.
Textbook of Organ Transplantation Set
In: Publications written by: Prof. Dr. Igor M. Sauer
Beautifully produced in full color throughout, and with over 600 high-quality illustrations, it successfully
- Provides a solid overview of what transplant clinicians/surgeons do, and with topics presented in an order that a clinician will encounter them.
- Presents a holistic look at transplantation, foregrounding the interrelationships between transplant team members and non-surgical clinicians in the subspecialties relevant to pre- and post-operative patient care, such as gastroenterology, nephrology, and cardiology.
- Offers a focused look at pediatric transplantation, and identifies the ways in which it significantly differs from transplantation in adults.
- Includes coverage of essential non-clinical topics such as transplant program management and administration; research design and data collection; transplant policy and bioethical issues.
Editors are Allan D. Kirk, Stuart J. Knechtle, Christian P. Larsen, Joren C. Madsen, Thomas C. Pearson, and Steven A. Webber.
I.M. Sauer, N. Raschzok und P. Neuhaus contributed chapter 47: „Artificial Liver, In Vivo Tissue Engineering, and Organ Printing – Solutions for Organ Scarcity“
The Wiley-Blackwell book (ISBN: 978-1-118-87014-3, 1880 pages) is available here.
Decellularization of porcine livers
In: Publications written by: Prof. Dr. Igor M. Sauer
Co-authors are K. Hillebrandt, R. Voitl, A. Butter, R.B. Schmuck, A. Reutzel-Selke, D. Geisel, K. Joehrens, P.A. Pickerodt, N. Raschzok, G. Puhl, P. Neuhaus, J. Pratschke, and I.M. Sauer.
Decellularization and recellularization of parenchymal organs may facilitate the generation of autologous functional liver organoids by repopulation of decellularized porcine liver matrices with induced liver cells. We present an accelerated (7 h overall perfusion time) and effective protocol for human scale liver decellularization by pressure-controlled perfusion with 1% Triton X-100 and 1% SDS via the hepatic artery (120 mmHg) and portal vein (60 mmHg). In addition, we analyzed the effect of oscillating pressure conditions on pig liver decellularization (n=12). The proprietary perfusion device used to generate these pressure conditions mimics intra-abdominal conditions during respiration to optimize microperfusion within livers and thus optimize the homogeneity of the decellularization process. The efficiency of perfusion decellularization was analyzed by macroscopic observation, histological staining (H&E, Sirius red, Alcian blue), immunohistochemical staining (collagen IV, laminin, fibronectin) and biochemical assessment (DNA, collagen, glycosaminoglycans) of decellularized liver matrices. The integrity of the extracellular matrix post-decellularization was visualized by corrosion casting and three-dimensional CT scanning. We found that livers perfused under oscillating pressure conditions (P+) showed a more homogenous course of decellularization and contained less DNA compared to livers perfused without oscillating pressure conditions (P-). Microscopically, livers from the (P-) group showed remnant cell clusters, while no cells were found in livers from the (P+) group. The grade of disruption of the ECM was higher in livers from the (P-) group, although the perfusion rates and pressure did not significantly differ. Immunohistochemical staining revealed that important matrix components were still present after decellularization. Corrosion casting showed an intact vascular (portal vein and hepatic artery) and biliary framework. In summary, the presented protocol for pig liver decellularization is quick (7 h) and effective. The application of oscillating pressure conditions improves the homogeneity of perfusion and thus the outcome of the decellularization process.
Tags: Decellularization,Liver
25th European Student´s Conference
In: Meetings written by: Prof. Dr. Igor M. Sauer
This year’s lecture series “Rethinking Medical Research – how do we achieve innovation?” will explore the dichotomy of medical advances by looking at both the opportunities and challenges that are presented to researchers and physicians. With topics ranging from open access policies, pharmaceutical innovations, and revolutionary health policies to advances in global health – we hope that this year’s topic will both challenge and inspire our participants!
The conference will take place from September 17th – 20th at the Virchow Klinikum Campus of the Charité Universitätsmedizin in Berlin, Germany.
More information here!
N. Raschzok Guest Editor - Call for Papers
In: Publications written by: Prof. Dr. Igor M. Sauer
Investigators are invited to participate in a special issue on „Human Pluripotent Stem Cells in Hepatic Development, Liver Reconstruction and Disease Modeling“ through original research articles at the forefront of this fast pace moving field as well as reviews describing current and forthcoming challenges.
Lead Guest Editor is Karim Si-Tayeb (Institute of the Thorax, Nantes). Guest Editors are Gareth Sullivan (Institute of Basic Medical Sciences, University of Oslo), Robert Schwartz (Weill Cornell Medical College, Cornell University, New York), Nathanael Raschzok (Charité – Universitaetsmedizin Berlin), and Tamir Rashid (King's College London).
Manuscript Due: Friday, 23 January 2015
First Round of Reviews: Friday, 17 April 2015
Publication Date: Friday, 12 June 2015
Tags: Call for papers
Kristina Kähm - Bachelor of Science
In: General |Bachelor written by: Prof. Dr. Igor M. Sauer
Her project was supervised in cooperation with Prof. Dr. Marcus Frohme, Division Molecular Biotechnology and Functional Genomics, Technical University of Applied Sciences in Wildau, Germany.
Tags: Decellularization