Biopolym. Cell. 2005; 21(3):230-249.
Our «Shagreen leather» is our problem. We have to solve it ourselves. 5. Forerunner
1Kordyum V. A.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


The problem of biological time and its difference from physical time (i. e. reversibility) is under discussion. Some issues of the problem usually identified as «struggle with aging» are under analysis. The possibilities of regenerative medicine are evaluated in connection with this question. The mechanism of purification (though not radical, but sufficiently effective) from the mutations accumulated in stem cells has been investigated. In the frame of the conception being developed the anabiosis and its incompatibility with the contemporary view of life are discussed. «The split of biological time» is being defined as a movement to a new level of knowledge.
Keywords: stem cells, regenerative medicine, biological time, mutations, anabiosis


[1] Rose M. Is it possible to slow down aging? Svit Nauki. 2003;(3-4):74-79.
[2] Scriver CR. Does hereditary metabolic disease modulate senescence and ageing? J Inherit Metab Dis. 2002;25(3):235-51.
[3] Gunsilius E, Gastl G, Petzer AL. Hematopoietic stem cells. Biomed Pharmacother. 2001;55(4):186-94.
[4] Till JE, McCulloch EA. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961;14:213-22.
[5] Oh IH, Kim DW. Three-dimensional approach to stem cell therapy. J Korean Med Sci. 2002;17(2):151-60.
[6] Taupin P, Gage FH. Adult neurogenesis and neural stem cells of the central nervous system in mammals. J Neurosci Res. 2002;69(6):745-9.
[7] Odorico JS, Kaufman DS, Thomson JA. Multilineage differentiation from human embryonic stem cell lines. Stem Cells. 2001;19(3):193-204.
[8] H?bner K, Fuhrmann G, Christenson LK, Kehler J, Reinbold R, De La Fuente R, Wood J, Strauss JF 3rd, Boiani M, Sch?ler HR. Derivation of oocytes from mouse embryonic stem cells. Science. 2003;300(5623):1251-6.
[9] Heddini A, Chen Q, Obiero J, Kai O, Fernandez V, Marsh K, Muller WA, Wahlgren M. Binding of Plasmodium falciparum-infected erythrocytes to soluble platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): frequent recognition by clinical isolates. Am J Trop Med Hyg. 2001;65(1):47-51.
[10] Weissman IL. Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science. 2000;287(5457):1442-6.
[11] Sanchez-Ramos JR. Neural cells derived from adult bone marrow and umbilical cord blood. J Neurosci Res. 2002;69(6):880-93.
[12] Ianus A, Holz GG, Theise ND, Hussain MA. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest. 2003;111(6):843-50.
[13] Okamoto R, Yajima T, Yamazaki M, Kanai T, Mukai M, Okamoto S, Ikeda Y, Hibi T, Inazawa J, Watanabe M. Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract. Nat Med. 2002;8(9):1011-7.
[14] Miyazaki M, Akiyama I, Sakaguchi M, Nakashima E, Okada M, Kataoka K, Huh NH. Improved conditions to induce hepatocytes from rat bone marrow cells in culture. Biochem Biophys Res Commun. 2002;298(1):24-30.
[15] Martin-Rendon E, Watt SM. Stem cell plasticity. Br J Haematol. 2003;122(6):877-91.
[16] Pereira RF, Halford KW, O'Hara MD, Leeper DB, Sokolov BP, Pollard MD, Bagasra O, Prockop DJ. Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci U S A. 1995;92(11):4857-61.
[17] Theise ND, Badve S, Saxena R, Henegariu O, Sell S, Crawford JM, Krause DS. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology. 2000;31(1):235-40.
[18] Chandra P, Coleman P, Mydosh JA, Tripathi V. Hidden orbital order in the heavy fermion metal URu(2)Si(2). Nature. 2002;417(6891):831-4.
[19] Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211-28.
[20] Evarts RP, Nagy P, Nakatsukasa H, Marsden E, Thorgeirsson SS. In vivo differentiation of rat liver oval cells into hepatocytes. Cancer Res. 1989;49(6):1541-7.
[21] Tatematsu M, Kaku T, Medline A, Farber E. Intestinal metaplasia as a common option of oval cells in relation to cholangiofibrosis in liver of rats exposed to 2-acetylaminofluorene. Lab Invest. 1985;52(4):354-62.
[22] Rao MS, Bendayan M, Kimbrough RD, Reddy JK. Characterization of pancreatic-type tissue in the liver of rat induced by polychlorinated biphenyls. J Histochem Cytochem. 1986;34(2):197-201.
[23] Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL. Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science. 1999;283(5401):534-7.
[24] Lagasse E, Shizuru JA, Uchida N, Tsukamoto A, Weissman IL. Toward regenerative medicine. Immunity. 2001;14(4):425-36.
[25] Wilkins LM, Watson SR, Prosky SJ, Meunier SF, Parenteau NL. Development of a bilayered living skin construct for clinical applications. Biotechnol Bioeng. 1994;43(8):747-56.
[26] Hoerstrup SP, Sodian R, Daebritz S, Wang J, Bacha EA, Martin DP, Moran AM, Guleserian KJ, Sperling JS, Kaushal S, Vacanti JP, Schoen FJ, Mayer JE Jr. Functional living trileaflet heart valves grown in vitro. Circulation. 2000;102(19 Suppl 3):III44-9.
[27] Atala A. Tissue engineering for the replacement of organ function in the genitourinary system. Am J Transplant. 2004;4 Suppl 6:58-73.
[28] Tuli R, Nandi S, Li WJ, Tuli S, Huang X, Manner PA, Laquerriere P, N?th U, Hall DJ, Tuan RS. Human mesenchymal progenitor cell-based tissue engineering of a single-unit osteochondral construct. Tissue Eng. 2004;10(7-8):1169-79.
[29] Hentz VR, Chang J. Tissue engineering for reconstruction of the thumb. N Engl J Med. 2001;344(20):1547-8.
[30] Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Sch?michen C, Nienaber CA, Freund M, Steinhoff G. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003;361(9351):45-6.
[31] Slaus M, Orli? D, Pe?ina M. Osteochondroma in a skeleton from an 11th century Croatian cemetery. Croat Med J. 2000;41(3):336-40.
[32] Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S. Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med. 2001;344(10):710-9.
[33] Gussoni E, Bennett RR, Muskiewicz KR, Meyerrose T, Nolta JA, Gilgoff I, Stein J, Chan YM, Lidov HG, B?nnemann CG, Von Moers A, Morris GE, Den Dunnen JT, Chamberlain JS, Kunkel LM, Weinberg K. Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. J Clin Invest. 2002;110(6):807-14.
[34] Cao Y, Vacanti JP, Paige KT, Upton J, Vacanti CA. Transplantation of chondrocytes utilizing a polymer-cell construct to produce tissue-engineered cartilage in the shape of a human ear. Plast Reconstr Surg. 1997;100(2):297-302.
[35] Bazopoulou-Kyrkanidou E. Chimeric creatures in Greek mythology and reflections in science. Am J Med Genet. 2001;100(1):66-80.
[36] Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function? Cell. 2001;105(7):829-41.
[37] Ronen A, Glickman BW. Human DNA repair genes. Environ Mol Mutagen. 2001;37(3):241-83.
[38] Friedberg EC. DNA damage and repair. Nature. 2003;421(6921):436-40.
[39] Kordyum VA. Our shagreen leather is our problem, and we have to solve it. 4. «Shagreenity» that makes our skin shagreen. Biopolym Cell. 2004; 20(4):267-89.
[40] Martin R. Chromosomal analysis of human spermatozoa. Preimplantat. Genet.: Proc. 1st Int. symp. (Chicago, Sept. 14-19, 1990). New York; London, 1991: 91-102.
[41] Martin RH, Barclay L, Hildebrand K, Ko E, Fowlow SB. Cytogenetic analysis of 400 sperm from three translocation heterozygotes. Hum Genet. 1990;86(1):33-9.
[42] Plachot M, Rougier N. Chromosomal analysis of oocytes and preembryos: Abstr. 6 Int. Conf. «Early Prenat. Diagn. Genet. Diseases from Gametes to Embryo* (Milan, 18-20 May, 1992). Prenat. Diagn. 1992. 12, Suppl: 26.
[43] Edwards RG. Causes of early embryonic loss in human pregnancy. Hum Reprod. 1986;1(3):185-98.
[44] Chernyshev VN, Savisko AA, Petrenko LI, Kutsev SI. Cytogenetic study of children with developmental disabilities, born in families Liquidator. Children's health and radiatsiya: current problems and solutions. M., 2001: 175-7.
[45] Zhao Y, Glesne D, Huberman E. A human peripheral blood monocyte-derived subset acts as pluripotent stem cells. Proc Natl Acad Sci U S A. 2003;100(5):2426-31.
[46] Kuwana M, Okazaki Y, Kodama H, Izumi K, Yasuoka H, Ogawa Y, Kawakami Y, Ikeda Y. Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation. J Leukoc Biol. 2003;74(5):833-45.
[47] Abuljadayel IS, Afghan RK, McCaffrey TA, Lundergan C, Hawley TS, Hawley RG, Dhoot GJ. SCID repopulating cells derived from unmobilised adult human peripheral blood. Curr Med Res Opin. 2004;20(1):87-100.
[48] Deng J, Steindler DA, Laywell ED, Petersen BE. Neural trans-differentiation potential of hepatic oval cells in the neonatal mouse brain. Exp Neurol. 2003;182(2):373-82.
[49] Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP. Bone marrow as a potential source of hepatic oval cells. Science. 1999;284(5417):1168-70.
[50] Dell'Agnola C, Rabascio C, Mancuso P, Capillo M, Pruneri G, Gobbi A, Minucci S, Ronzoni S, Volorio S, Calabrese L, Tradati N, Martinelli G, Shultz L, Bertolini F. In vitro and in vivo hematopoietic potential of human stem cells residing in muscle tissue. Exp Hematol. 2002;30(8):905-14.
[51] Asakura A. Stem cells in adult skeletal muscle. Trends Cardiovasc Med. 2003;13(3):123-8.
[52] Cousin B, Andr? M, Arnaud E, P?nicaud L, Casteilla L. Reconstitution of lethally irradiated mice by cells isolated from adipose tissue. Biochem Biophys Res Commun. 2003;301(4):1016-22.
[53] Suva D, Garavaglia G, Menetrey J, Chapuis B, Hoffmeyer P, Bernheim L, Kindler V. Non-hematopoietic human bone marrow contains long-lasting, pluripotential mesenchymal stem cells. J Cell Physiol. 2004;198(1):110-8.
[54] Leskel? HV, Risteli J, Niskanen S, Koivunen J, Ivaska KK, Lehenkari P. Osteoblast recruitment from stem cells does not decrease by age at late adulthood. Biochem Biophys Res Commun. 2003;311(4):1008-13.
[55] Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, Piatyszek MA, Shay JW, Ishioka S, Yamakido M. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol. 1995;155(8):3711-5.
[56] Norrback KF, Dahlenborg K, Carlsson R, Roos G. Telomerase activation in normal B lymphocytes and non-Hodgkin's lymphomas. Blood. 1996;88(1):222-9.
[57] Wu K, Volke A, Lund M, Bang K, Thestrup-Pedersen K. Telomerase activity is spontaneously increased in lymphocytes from patients with atopic dermatitis and correlates with cellular proliferation. J Dermatol Sci. 1999;22(1):24-30.
[58] Lanza RP, Cibelli JB, West MD. Human therapeutic cloning. Nat Med. 1999;5(9):975-7.
[59] Koh CJ, Atala A. Therapeutic cloning applications for organ transplantation. Transpl Immunol. 2004;12(3-4):193-201.
[60] Great Soviet Encyclopedia. Ed. Prokhorov. M .: Soviet encyclopedia, 1969; vol 1.
[61] Clegg JS. Cryptobiosis--a peculiar state of biological organization. Comp Biochem Physiol B Biochem Mol Biol. 2001;128(4):613-24.
[62] Nenashev VA, Pridachina NN, El'-Registran GI, Zolotareva IN, Batrakov SG. [Effect of autoinducers of anabiosis for some microorganisms on rat liver mitochondria respiration]. Biokhimiia. 1994;59(1):11-5.
[63] Kolpakov AI, Il'inskaia ON, Bespalov MM, Kupriianova-Ashina FG, Gal'chenko VF, Kurganov BI, El'-Registan GI. [Stabilization of enzymes by anabiosis autoinducers as a possible mechanism of resistance of resting microbial forms]. Mikrobiologiia. 2000;69(2):224-30.
[64] Goldovsky AM, Ivanova EV. The action of oxygen on cells under complete anabiosis. Tsitologiia. 1984. 26(11):1321-3.
[65] Aksenov SI. [Limit of duration of anabiosis in microorganisms]. Mikrobiologiia. 1982;51(5):877-80.
[66] Hofreiter M, Jaenicke V, Serre D, von Haeseler A, P??bo S. DNA sequences from multiple amplifications reveal artifacts induced by cytosine deamination in ancient DNA. Nucleic Acids Res. 2001;29(23):4793-9.