Tissue engineering

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Principle of tissue engineering

Tissue Engineering (TE) ( engl. For tissue engineering and tissue engineering) or tissue culture is the generic term for the artificial production of biological tissue by the directed cultivation of cells , in order to replace diseased tissue in a patient or to regenerate.

properties

In tissue engineering, cells are usually taken from the donor organism and multiplied in vitro in the laboratory . Depending on the type of cell, these can be cultivated two-dimensionally as a cell lawn or three-dimensionally using certain cell structures. They can then be (re-) transplanted to the recipient. These can then usually be implanted in the same organism and thus maintain or restore tissue function. Tissue engineering products (TEP) belong to the group of drugs for advanced therapies and are one of the application examples for regenerative and personalized medicine .

“Tissue engineering is the application of principles and methods from engineering, materials and life sciences to gain a fundamental understanding of structure-function relationships in normal and pathological mammalian tissues; and the development of biological substitutes to renew, maintain or improve tissue function ”. In a narrower sense, it means taking cells from the patient to grow the desired organ.

Tissue engineering includes four elements, viz

  1. a structural framework (optional, often called a scaffold )
  2. living cells or tissues
  3. the control of signal transduction to the living component ( growth factors )
  4. a culture medium (nutrient solution) or organism.
Tissue culture in culture flasks containing a nutrient medium containing

The scaffold of a biological or synthetic type is combined with the removed vital material to form a 3D cell culture before the culture . Cultivation can take place both in the body ( in-vivo tissue engineering) and in the laboratory ( in-vitro tissue engineering). In both cases, the signaling substances that reach the cell are ideally controlled so that the formation of the new tissue is supported. Some of the cells can also be printed on a surface with a bioprinter .

The regenerates or constructs are implanted into the target region of the organism by adoptive cell transfer . The advantage of such an implant with an autologous (patient's own) cell component is that it is accepted by the patient's immune system , because the cultured cells only have proteins on the cell surfaces that the immune system recognizes as "its own". This should not normally reject tissue engineering implants. A good example of this is the production of completely autologous heart valves or vascular prostheses, which are used when, for example, a clogged artery cannot be replaced by an endogenous vein. In such a case, a plastic prosthesis is usually used, which is an unsatisfactory alternative.

Bioreactor system for the cultivation of vascular prostheses
Vascular prosthesis made by tissue engineering
Tissue engineered heart valve

The problem with tissue engineering is that specified cells lose their functionality ( dedifferentiation ). An animal study in adult sheep, in which autologous vascular prostheses were implanted, showed continuous vessels that built up a solid tissue by the end of the experiment. So far it has been possible to grow skin and cartilage tissue as well as blood vessels for commercial use.

In most cases, already differentiated cells from the organism are multiplied in vitro. A new approach is the use of adult or induced pluripotent stem cells (iPS). The adult cells can be obtained from the bone marrow or internal organs of adults and the iPS can be generated by reprogramming cells (e.g. fibroblasts from the skin). The stem cells can be multiplied in the culture container and then differentiated into certain required cell types using chemicals.

The driving force behind the development of tissue engineering is the increasing need for safe replacement tissues and organs as well as basic research.

In general, there are four types of implants:

  • from other living beings ( xenogeneic ) - z. B. Heart valves
  • from an individual of the same species ( allogeneic ) - e.g. B. kidney
  • by the patient himself ( autologous ) - e.g. B. Skin
  • of genetically identical individuals ( syngeneic ) - such as B. of identical twins

Applications

The TE approaches that have so far been successful are exclusively tissue from a single type of cell. Cartilage tissue is particularly suitable for tissue culture, since cartilage already consists of a single type of cell in the living body, is only nourished by the synovial fluid and produces its own framework from collagen fibers and proteoglycans. Other vital tissues, such as B. liver or kidney parenchyma, are so complex in their structure that in vitro cultivation has not been successful. In order to be able to use the effectiveness of the specific organ cells in life-threatening diseases, the parenchymal cells have previously been exposed to the blood stream in dialysis systems. For tissue engineering of functioning organs, in addition to the parenchymal cells (e.g. hepatocytes ), supporting tissue, blood vessels and bile vessels, possibly also lymph vessels, would have to be grown. Cocultures of such different cell types are a challenge for the future. Cocultures have heretofore been performed for chondrocytes and osteoblasts as well as endothelial cells and vascular smooth muscle cells. Until these coculture problems are resolved, TE will not achieve the great goals of organ breeding for vital organs. Only then are transplants of donor organs replaced by the targeted cultivation of organs with the help of the body's own cells.

Another important application of tissue engineering is its use in basic research. Constructs based on natural tissue are used there to elucidate cellular mechanisms. In addition, the methods of TE enable the production of three-dimensional tissue-like cell constructs on which the effects of pollutants (e.g. pesticides) as well as the effects of pharmaceuticals can be tested. It is possible that there will be another application in the future in the biotechnological production of in-vitro meat in order to circumvent factory farming and the problems associated with it.

At the end of February 2018, an Israeli medical team succeeded in growing and successfully implanting tissue for a shin bone for the first time. The stem cells for this were previously taken from the patient's fatty tissue.

literature

Web links

Commons : Tissue engineering  - collection of images, videos and audio files

Individual evidence

  1. ↑ Toni Lindl, Gerhard Gstraunthaler: cell and tissue culture: From the basics to the bench. Spectrum Akademischer Verlag, Heidelberg 2008, ISBN 978-3-8274-1776-3 .
  2. ↑ Richard Skalak (ed.): Tissue Engineering . Liss, New York 1988, ISBN 0-8451-4706-4 .
  3. ↑ autologous heart valves ( memento of the original from October 3, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.ame.hia.rwth-aachen.de
  4. ↑ Vascular prostheses ( Memento of the original from October 3, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.ame.hia.rwth-aachen.de
  5. ↑ S. Koch, TC Flanagan, JS Sachweh, F. Tanios, H. Schnoering, T. Deichmann, V. Ellä, M. Kellomäki, N. Gronloh, T. Gries, R. Tolba, T. Schmitz-Rode, p Jockenhoevel: Fibrin-polylactide-based tissue-engineered vascular graft in the arterial circulation. In: Biomaterials. Volume 31, Issue 17, 2010, pp. 4731-4739. Epub 2010 Mar 20, PMID 20304484 .
  6. ↑ Y. Kuroyanagi, M. Kenmochi, S. Ishihara, A. Takeda, A. Shiraishi, N. Ootake, E. Uchinuma, K. Torikai, N. Shioya: A cultured skin substitute composed of fibroblasts and keratinocytes with a collagen matrix : preliminary results of clinical trials (A cultured skin substitute made from fibroblasts, keratinocytes and collagen matrix: preliminary results of a clinical study). In: Ann Plast Surg. Volume 31, Issue 4, 1993, pp. 340-349; Discussion pp. 349-351, PMID 8239435 .
  7. ↑ A. Haisch, O. Schultz, C. Perka, V. Jahnke, GR Burmester, M. Sittinger: Tissue engineering of human cartilage tissue for reconstructive surgery using biocompatible fibrin gels and polymer carriers [Tissue engineering of human cartilage tissue for reconstructive surgery using biocompatible resorbable fibrin gel and polymer carriers]. In: ENT. Volume 44, Issue 11, 1996, pp. 624-629, PMID 9064296 .
  8. ^ SQ Liu: Prevention of focal intimal hyperplasia in rat vein grafts by using a tissue engineering approach. In: Atherosclerosis. Volume 140, Issue 2, 1998, pp. 365-377, doi: 10.1016 / S0021-9150 (98) 00143-9 .
  9. ↑ Erich Wintermantel , Suk-Woo Ha: Medical technology with biocompatible materials and processes. Springer Verlag, Berlin Heidelberg New York 2002, ISBN 3-540-41261-1 .
  10. ↑ J. Heine, A. Schmiedl, S. Cebotari, H. Mertsching, M. Karck, A. Haverich, K. Kallenbach: Preclinical assessment of a tissue-engineered vasomotive human small-calibered vessel based on a decellularized xenogenic matrix: histological and functional characterization. In: Tissue Eng. Part A, Volume 17, 2011, pp. 1253-1261, doi: 10.1089 / ten.tea.2010.0375 .
  11. ↑ NM Meenen: Tissue engineering - a position assessment. In: ZOrthop accident. Volume 146, 2008, pp. 19-20, doi: 10.1055 / s-2008-1038354 (free full text).
  12. ↑ K. Andreas, C. Lübke, T. Häupl u. a .: Key regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitro study (Central regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitro study) . In: Arthritis Research & Therapy . Edition v10n1 from January 18, 2008. BioMed Central, London 2008, doi: 10.1186 / ar2358 , PMC 2374452 (free full text).
  13. ↑ Bone substitute: A shin bone from a test tube . In: FAZ.NET . February 28, 2018, ISSN  0174-4909 ( faz.net [accessed March 13, 2018]).