Miniature human liver the latest achievement of tissue engineering

During the last year’s meeting of The American Association for the Study of Liver Diseases(1) (AASLD) the innovative technique of bioscaffolding has been presented. On the basis of this novelty scientists managed to produce a fully functional liver ­ a hybrid of animal and human cells. This is the next important step in regenerative medicine.

Regenerative medicine is a relatively new branch of medical sciences. It’s main aim is to treat illnesses by exchanging old and unhealthy cells for young ones and untouched by pathological processes. The weapon for regenerative medicine is not only the use of stem cells and gene therapy but also tissue engineering. This discipline tries to find out a way to replace the defective elements of human body by new tissues created in vitro. Medical knowledge and methods of materials science can make it happen. The idea of regenerative medicine has already been adopted, various types of skin or cartilage implants that were grown in laboratories are currently used in clinical practice.

To produce a three-dimensional tissue culture a special matrix is required. It is often defined as a bioscaffold. As the creation of proper tissues in vitro demands intensive culturing to promote survival, growth and developing functionality of the culture, the bioscaffold needs to be very special. Until recently bioscaffolds made of porous biomaterials, both naturally derived (like collagen polymers) and synthetic (e.g. silicone) have been used. But unfortunately they do not provide the constant supply of nutritients for a future organ, so that it could mimic the natural vascular system.

In 2009 a group of scientists from Wake Forest Institute for Regenerative Medicine in Winston-Salem proved that the problem presented above can be solved(2). They used an innovative method of obtaining bioscaffolds. The scientists performed the so ­called decellularization of an organ gained from an experimental animal to ˈseedˈ it with human cells. In order to do that, selective detergents were used to eliminate the cellular component and leave the extracellular matrix as well as the vascular network intact. This technique may serve in building organs like liver, kidney, pancreas and intestine. Other scientific groups have already started testing bioscaffolds for cornea(3) and aortic valve(4).

Further research results were presented in October 2010 during the AASLDˈs annual meeting(5). For the first time a human hepatic tissue based on an animal scaffold has been produced. Human fetal liver progenitor cells (hFLPCs) and endothelial cells were placed into the bioscaffold by vena cava or portal vein. The culture was kept in a bioreactor for one week with constant culture medium perfusion. Next, the results were evaluated by means of microscopy, immunohistochemistry in order to detect the production of albumins, alpha­fetoprotein, prostacyclin and urea. The proliferative activity was measured by means of Ki67 protein expression, the process of apoptosis by TUNEL method. The results of the above mentioned tests proved that the culture functionally resembles natural hepatocytes.

The latest findings indicate that regenerative medicine has recently achieved one of its primary goals. But the road is winding and still many tests have to be performed until the bioscaffold is used in transplantology. Despite a long list of potential candidates for liver transplant, pharmacological and toxicological research has to be carried out so as to estimate the safety of this method. Next step is the attempt to implant an artificial organ to an experimental animal. Nevertheless, the head of research team, Pedro Baptista believes that transplanted liver will develop and maintain its functions(6).

Written by: Natalia Neumann

Bibliography:

1. http://www.aasld.org/lm/Pages/Default.aspx
2. http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?arnumber=5333145
3. http://www.ncbi.nlm.nih.gov/pubmed/20956275
4. http://www.ncbi.nlm.nih.gov/pubmed/20434354
5. http://www.aasld.org/LM/PRESS/Pages/PressReleaseBioengineered.aspx
6. http://www.medpagetoday.com/MeetingCoverage/AASLD/23073

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