Human Genetics and Genetic Diseases

Biography

Biography: Ryszard Slomski

Abstract

Statement of the Problem:

The growing shortage of available organs is a major problem in transplantology. The promising solution could be xenotransplantation, i.e., the use of cells, tissues and organs of domestic pig. However, xenogeneic transplantation from pigs to humans involves high immune incompatibility and a complex rejection process. The rapid development of genetic engineering techniques enables genome modifications in pigs that reduce the cross-species immune barrier. The purpose of this study is to develop the technology to use transgenic pigs for biomedical purposes. The Project is an alternative to studies using stem cells and work aiming at the production of artificial organs.

Methodology & Theoretical Orientation: Development of an animal breeding system and the collection of skin, valves and blood vessels from transgenic pigs. The project involves also production of polytransgenic pigs using reproduction biotechnology methods. Very important was development and characteristics of gene constructs preventing xenotransplant rejection and multiparametric characteristics of transgenic animals. Tissues of transgenic animals were used for treatment of human cardiovascular diseases using vessels and cardiac valve bioprostheses. Biological dressings were obtained from skin of transgenic pigs.

Findings: Important issues in production of transgenic animals are characteristics of transgene, transfection and cell transformation, detection of transgene integration, mapping of transgene, passing specific traits to the offspring, homozygote selection, analysis of transgene activity and function. Fully characterized transgenic animals carrying three or more modifications may be used as sources of skin, heart valves or vessels.

Conclusion & Significance: Transgenic animals were generated using traditional methods and new genome editing technologies. Tissues of transgenic animals used in experimental studies showed growing potential in use as alternative treatment of human. This work was supported by grant No. INNOMED/I/17/NCBR/2014 from the National Centre for Research and Development.

Image:

Recent Publications (minimum 5)

1. Hryhorowicz M, Lipiński D, Zeyland J, Słomski R (2017) CRISPR/Cas9 Immune System as a Tool for Genome Engineering. Archivum Immunologiae et Therapiae Experimentalis 65:233-240.
2. Hryhorowicz M, Zeyland J, Słomski R, Lipiński D (2017) Genetically Modified Pigs as Organ Donors for Xenotransplantation. Molecular Biotechnology 59:435-444.
3. Kimsa-Dudek M, Strzalka-Mrozik B, Kimsa MW, Blecharz I, Gola J, Skowronek B, Janiszewski A, Lipinski D, Zeyland J, Szalata M, Slomski R, Mazurek U (2015) Screening pigs for xenotransplantation: expression of porcine endogenous retroviruses in transgenic pig skin. Transgenic Research 24:529-536.
4. Wilczek P, Lesiak A, Niemiec-Cyganek A, Kubin B, Slomski R, Nozynski J, Wilczek G, Mzyk A, Gramatyka M (2015) Biomechanical properties of hybrid heart valve prosthesis utilizing the pigs that do not express the galactose-α-1,3-galactose (α-Gal) antigen derived tissue and tissue engineering technique. Journal of materials science. Materials in Medicine 26:5329.
5. Cierpka L, Ryszka F, Dolińska B, Smorąg Z, Słomski R, Wiaderkiewicz R, Caban A, Budziński G, Oczkowicz G, Wieczorek J (2014) Biolasol: novel perfusion and preservation solution for kidneys. Transplantation Proceedings 46:2539-2541.