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MIC-1 in regenerative medicine

Renewal processes are connected to the presence of adult stem cells in tissues and organs and their heterogeneous populations in blood which,when necessary, are released from bone marrow. These cells are capable of multipotent differentiation in an adult organism (8). Lack of major histocompatibility complexes class two (MHCII) and repressing activity of T and B lymphocytes, prevents the rejection of allograft and xenograft transplants using stem cells (9-12). Another attribute of these stem cells is the possibility to obtain a larger amount of them in an in-vitro culture in comparison to culture of more differentiated cells.

Stem cells are not only used in tissue engineering for the repair of damaged tissue, but they also are more and more often used in gene therapy as active cells producing growth factors (FGF – fi broblast growth factor, VEGF – vascular endothelial growth factor, BMP4 – bone morphogenic protein 4) as well as a transcription factor Sox-9, which accelerates the regeneration process of, for example, heart, bones and cartilage (13-15).
 
The dynamic antler growth process of cervids requiers activation and involvement of multiple types of cells. Essential role in initiation and continuation of this process have the stem cells. A stable line of antlerogenic MIC-1 cells (the line’s name entered in patents)
- adult mezenchymal stem cells – was derived from the growing antler of red deer (Cervus elaphus). Cultured cells are characterized by rapid growing and are virtually „immortal”, they require uncomplicated, standard procedures that are generally accepted and applied in cell culture laboratories. They are easy to transport, as well as freeze and store in liquid nitrogen.

List of publications:
1. Vogel G.: How can a skin cell become a nerve cell? Science 2005, 309: 85.
2. Alison M.R., Poulsom R., Forbes S., Wright N.A.: An introduction to stem cells. J. Pathol. 2002, 197: 419–423.
3. Cegielski M., Całkosiński I., Dzięgiel P., Zabel M.: Search for stem cells for pulmonary alveolar epithelium. Bull. Vet. Inst. Pulawy 2004, 48: 471–475.
4. Cogle C.R., Guthrie S.M., Sanders R.C., Allen W.L., Scott E.W., Petersen B.E.: An overview of steam cell research and regulatory issues. Mayo Clin. Proc. 2003, 78: 993–1003.
5. Lee O.K., Kuo T.K., Chen W.M., Lee K.D., Hsieh S.L., Chen T.H.: Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 2004, 103: 1669–1675.
6. Emura M.: Stem cells of the respiratory epithelium and their in vitro cultivation. In Vitro Cell. Dev. Biol. Anim. 1997, 33: 3–14.
7. Zhou S., Schuetz J.D., Bunting K.D., Colapietro A.M., Sampath J., Morris J.J., Lagutina I., Grosveld G.C., Osawa M., Nakauchi H., Sorrentino B.P.: The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat. Med. 2001, 7: 1028–1034.
8. Pituch-Noworolska A., Majka M., Janowska-Wieczorek A., Baj-Krzyworzeka M., Urbanowicz B., Malec E., Ratajczak M.Z.: Circulating CXCR4-positive stem/progenitor cells compete for SDF-1 positive niches in bone marrow, muscle and neural tissues: an alternative hypothesis to stem cell plasticity. Folia Histochem. Cytobiol. 2003, 41: 13–21.
9. Bartholomew A., Sturgeon C., Siatskas M., Ferrer K., McIntosh K., Patil S., Hardy W., Devine S., Ucker D., Deans R., Moseley A., Hoff man R.: Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp. Hematol. 2002, 30: 42–48.
10. Chamberlain G., Fox J., Ashton B., Middleton J.: Concise review: mesenchymal stem cells: their phenotype, diff erentiation capacity, immunological features, and potential for homing. Stem Cells 2007, 25: 2739–2749.
11. Corcione A., Benvenuto F., Ferretti E., Giunti D., Cappiello V., Cazzanti F., Risso M., Gualandi F., Mancardi G.L., Pistoia V., Uccelli A.: Human mesenchymal stem cells modulate B-cell functions. Blood 2006, 107: 367–372.
12. Javazon E.H., Beggs K.J., Flake A.W.: Mesenchymal stem cells: paradoxes of passaging. Exp. Hematol. 2004, 32: 414–425.
13. Matsumoto R., Omura T., Yoshiyama M., Hayashi T., Inamoto S., Koh K.R., Ohta K., Izumi Y., Nakamura Y., Akioka K., Kitaura Y., Takeuchi K., Yoshikawa J.: Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction. Arterioscler. Thromb. Vasc. Biol. 2005, 25: 1168–1173.
14. Tsuchiya H., Kitoh H., Sugiura F., Ishiguro N.: Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells. Biochem. Biophys. Res. Commun. 2003, 301: 338–343.
15. Zhang X.S., Linkhart T.A., Chen S.T., Peng H., Wergedal J.E., Guttierez G.G., Sheng M.H., Lau K.H., Baylink D.J.: Local ex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in mice. J. Gene Med. 2004, 6: 4–15.

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