Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Xenotransplantation – no replication of porcine endogenous retroviruses in human cell culture

27.01.2014
Transplantations of animal cells, tissues, or organs to humans (xenotransplantion) could in future solve the problem of short organ supply.

It must, however, be guaranteed that no pathogenic agents from animals are transmitted to the human body. Researchers at the Paul-Ehrlich-Institut have now been able to prove that although porcine endogenous retroviruses (PERV) can penetrate human blood cells under certain circumstances, they cannot replicate at these sites.


TEM-Photo: Porcine endogenous retrovirus (PERV). Green: infected cell cytoplasma; pink: so-called clathrin-coated pit; yellow: virus particle; red: virus core; blue: genetic material of the virus

Source: Dr. Klaus Boller, Paul-Ehrlich-Institut

In connection with screening methods, the aim is to minimize the risk of transmission of PERV by the xenotransplant. The journal Xenotransplantation reports on the results of these research activities in its latest online edition.

Patients often have to face long waiting periods before they can receive an organ suitable for transplantation. This has not only been a problem since the transplantation scandal of last year. Pigs have been the subject of research as a possible organ donor for a long time. First clinical trials using insulin producing cells of the porcine pancreas in patients with type-1 diabetes are already underway in New Zealand and Argentina. Transplantations of whole animal organs such as porcine hearts or kidneys are also thinkable as a medium-term solution and are studied extensively. However, a transplantation of organs from other species to humans presents the risk that endogenous retroviruses, which form an integral part of the genome of the donor animals, will be transmitted in the form of replication-competent virus particles thus causing infections. Porcine endogenous retroviruses (PERV) present in pigs are closely related to retroviruses, which can cause leukaemia in mice, cats, or gibbons. It is therefore assumed that PERV can also cause such diseases after transmission to humans.

A research team of Professor Ralf R. Tönjes, head of the section "Non-vital Tissue Preparations, Xenogeneic Cell Therapeutics" of the Division "Medical Biotechnology" at the Paul-Ehrlich-Institut has investigated whether PERV can really infect human blood cells [1]. Although the investigators at the PEI performed their experiments in vitro, they created conditions as close as possible to the situation of a xenotransplantation to study the real risk of a PERV infection. The porcine cells were co-cultured with human lymphocytes over a period of one month – the human cells and the animal cells were separated from each other only by a membrane permeable for viruses. The researchers established that the PERV could pass the membrane and penetrate the human lymphocytes to a lesser extent. The viral DNA was then identified in these lymphocytes. However, this DNA was not functional, i.e. the genetic information could not be used by the cells to produce new intact virus particles. Productive infection involving the development of new infectious PERV was indeed not observed.

Besides, before xenotransplantations, safety experts have expressed that they require a two-step analysis of the transplant for transmissible PERV involving genetic screening and an assay with a highly sensitive human cell line. This test must be able to show that no functional PERV is present.

"Being a federal institute responsible for the authorisation of clinical trials on xenogeneic cell therapeutics, we require steps from the manufacturers and users which keep the risk of transmission of pathogenic agents during xenotransplantations to a minimum. Our experiments, which use the best screening methods currently available, indicate that no infectivity to human blood cells by PERV causing a disease would occur during xenotransplantations", as Professor Tönjes explained when discussing the research results. Even if transmission of PERV occurred, human blood cells are equipped with cellular protective mechanisms against these viruses and would counteract them in the various phases of the replication cycle [2].

Professor Tönjes and his co-workers are part of the special research group (Sonderforschungsbereich, SFB /Transregio 127) "Biologie der xenogenen Zell- und Organtransplantation – vom Labor in die Klinik" (Biology of xenogeneic cell, tissue and organ transplantation – from bench to bedside) with 16 sub-groups in Berlin, Dresden, Hannover, Langen and München. This research group is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).

Original publication:
Rodrigues Costa M, Fischer N, Gulich B, Tönjes RR (2014): Comparison of porcine endogenous retroviruses infectious potential in supernatants of producer cells and in cocultures.

Xenotransplantation Jan 21 [Epub ahead of print]. DOI: 10.1111/xen.12081

Literature:
[1] Specke V et al.: Productive infection of human primary cells and cell lines with porcine endogenous retroviruses. Virology. 2001;285(2):177-180

[2] Denner J, Tönjes RR. Infection Barriers to Successful Xenotransplantation Focusing on Porcine Endogenous Retroviruses. Clinical Microbiology Reviews 2012;25(2):318-343

The Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, in Langen near Frankfurt/Main is a senior federal authority reporting to the Federal Ministry of Health (Bundesministerium für Gesundheit, BMG). It is responsible for the research, assessment, and marketing authorisation of biomedicines for human use and veterinary vaccines. Its remit also includes the authorisation of clinical trials and pharmacovigilance, i.e. recording and evaluation of potential adverse effects.

Other duties of the institute include official batch control, scientific advice and inspections. In-house experimental research in the field of biomedicines and life science form an indispensable basis for the varied and many tasks performed at the institute.

The Paul-Ehrlich-Institut, with its roughly 800 members of staff, also has advisory functions nationally (federal government, federal states (Länder)), and internationally (World Health Organisation, European Medicines Agency, European Commission, Council of Europe etc.).

Weitere Informationen:

http://onlinelibrary.wiley.com/doi/10.1111/xen.12081/abstract Original Publication, Abstract

http://www.pei.de/EN/information/journalists-press/press-releases/2014/01-xenotransplantation-no-replication-porcine-endogenous-retroviruses.html

Press Release on the Paul-Ehrlich-Institut Website

Dr. Susanne Stöcker | idw
Further information:
http://www.pei.de

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Solar Collectors from Ultra-High Performance Concrete Combine Energy Efficiency and Aesthetics

16.01.2017 | Trade Fair News

3D scans for the automotive industry

16.01.2017 | Automotive Engineering

Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs

16.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>