21 Íîâîñòè êëåòî÷íûõ òåõíîëîãèé ËÈÒÅÐÀÒÓÐÀ: 1. Avital I., Inderbitzin D., Aoki T. et al. Isolation, characterization, and transplantation of bone marrow-derived hepatocyte stem cells. Biochem. Biophys. Res. Commun. 2001; 288(1): 156-64. 2. Inderbitzin D., Avital I., Gloor B. et al. Functional comparison of bone marrowderived liver stem cells: selection strategy for cell-based therapy. J. Gastrointest. Surg. 2005; 9(9): 1340-5. 3. Kucia M., Dawn B., Hunt G. et al. Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction. Circ. Res. 2004; 95(12): 1191-9. 4. Kucia M., Ratajczak J., Reca R. et al. Tissue-specific muscle, neural and liver stem/progenitor cells reside in the bone marrow, respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury. Blood Cells Mol. Dis. 2004; 32(1): 52-7. 5. Wojakowski W., Tendera M., Michalowska A. et al. Mobilization of CD34/ CXCR4+, CD34/ CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circ. 2004; 110: 321320. 6. Kucia M., Ratajczak J., Ratajczak M.Z. Bone marrow as a source of circulating CXCR4 + tissue-committed stem cells. Biol. Cell 2005; 97: 13346. 7. Goolsby J., Marty M.C., Heletz D. et al. Hematopoietic progenitors express neural genes. Proc. Natl. Acad. Sci. USA 2003; 100(25): 14926-31. 8. Tondreau T., Lagneaux L., Dejeneffe M. et al. Bone marrow-derived mesenchymal stem cells already express specific neural proteins before any differentiation. Differentiation 2004; 72(7): 319-26. 9. Willenbring H., Bailey A.S., Foster M. et al. Myelomonocytic cells are sufficient for therapeutic cell fusion in liver. Nat. Med. 2004; 10; 7: 744-8. Ïîäãîòîâèë À.Ë. Ïîñïåëîâ Ïî ìàòåðèàëàì Leukemia 2006; 20: 18-28 Ñîçäàíèå ôóíêöèîíàëüíîé òêàíè ìîëî÷íîé æåëåçû èç îäíîé ñòâîëîâîé êëåòêè Èäåÿ î ñóùåñòâîâàíèè ñòâîëîâûõ êëåòîê ýïèòåëèÿ ìîëî÷íîé æåëåçû (ÑÊÌÆ) âîçíèêëà åùå â íà÷àëå 60-õ ãã. ïðîøëîãî âåêà, îäíàêî, å¸ ýêñïåðèìåíòàëüíûå ïîäòâåðæäåíèÿ ñòàëè ïîÿâëÿòüñÿ ëèøü â ïîñëåäíèå ãîäû [1].  1998 ã. Kordon è Smith ïðîèçâîäèëè ñåðèéíûå òðàíñïëàíòàöèè ôðàãìåíòîâ ýïèòåëèàëüíîé òêàíè æåëåçû ìûøåé è ïîêàçàëè, ÷òî â òêàíè æåëåçû ïðèñóòñòâóþò êëåòêè, êîòîðûå ñïîñîáíû ñàìîîáíîâëÿòüñÿ è ìîãóò ïîëíîñòüþ âîñïðîèçâîäèòü ýïèòåëèàëüíóþ òêàíü ìîëî÷íîé æåëåçû (ÌÆ) â íåñêîëüêèõ ïîêîëåíèÿõ [1]. Èíòåðåñ ê ÑÊÌÆ ñòàë âîçðàñòàòü ñ ïîÿâëåíèåì ðàáîò, â êîòîðûõ ãîâîðèòñÿ î âêëàäå ýòèõ êëåòîê â çëîêà÷åñòâåííîå ïåðåðîæäåíèå ýïèòåëèÿ ÌÆ [2]. Îäíàêî òî÷íàÿ èäåíòèôèêàöèÿ ïîïóëÿöèè ñòâîëîâûõ êëåòîê ìîëî÷íîé æåëåçû îñòàâàëàñü íåâûïîëíåííîé çàäà÷åé, ò.ê. íå áûëî ïðåäëîæåíî áèîõèìè÷åñêèõ è ôóíêöèîíàëüíûõ ìàðêåðîâ, õîðîøî õàðàêòåðèçóþùèõ ýòè êëåòêè.  ñîâìåñòíîé ìåæäóíàðîäíîé ðàáîòå àìåðèêàíñêèõ, àâñòðàëèéñêèõ è êàíàäñêèõ ó÷åíûõ, îïóáëèêîâàííîé â æóðíàëå Nature, äîñòîâåðíî ïîêàçàíî ïîëó÷åíèå ôóíêöèîíèðóþùåé òêàíè ìîëî÷íîé æåëåçû èç ñîáñòâåííûõ ÑÊÌÆ ìûøè in vivo. Ó÷åíûå âïåðâûå âûäåëèëè ïîïóëÿöèþ èñòèííûõ êëîíîãåííûõ ìóëüòèïîòåíòíûõ ÑÊÌÆ, ñïîñîáíóþ ê ñàìîîáíîâëåíèþ. Âûäåëåíèå èíòåðåñóþùåé ïîïóëÿöèè êëåòîê ïðîèçâîäèëîñü ñ èñïîëüçîâàíèåì ôëóîðåñöåíòíîãî ñîðòèíãà èç òîòàëüíîãî ãîìîãåíàòà òêàíè ÌÆ, îáðàáîòàííîãî ôåðìåíòàìè. Èçîëèðîâàíûå Lin- è Lin+ êëåòêè áûëè ïîäñàæåíû â ìåæäîëüêîâóþ æèðîâóþ òêàíü. Ýôôåêòèâíîñòü òðàíñïëàíòàöèè èçìåðÿëàñü ïî ÷àñòîòå ôîðìèðîâàíèÿ ðåïîïóëèðóþùèõ åäèíèö æåëåçû (mammary repopulating units (MRUs)). MRU ôîðìèðîâàëèñü òîëüêî ïîñëå òðàíñïëàíòàöèè Lin- êëåòîê, êîòîðûå áûëè ðàçäåëåíû íà ÷åòûðå ñóáïîïóëÿöèè íà îñíîâå ýêñïðåññèè CD29 (β-1-integrin) è CD24 (heat-stable antigen). Ýêñïðåññèÿ ýòèõ ìàðê¸ðîâ èçâåñòíà äëÿ íåéðîíàëüíûõ ñòâîëîâûõ êëåòîê è îïóõîëåé ÌÆ [2]. Ýôôåêòèâíîñòü è ÷àñòîòà ôîðìèðîâàíèÿ MRU òîé èëè èíîé ôðàêöèåé âûÿñíÿëàñü ïîñëå ñîðòèíãà êëåòîê è èõ ïîñëåäóþùåé ïåðåñàäêè. Òàê, áûëî ïîêàçàíî, ÷òî òðàíñïëàíòàöèÿ òîëüêî Lin-/CD29hi/CD24+ ïîïóëÿöèè ïðèâîäèëà ê ñòàáèëüíîìó ôîðìèðîâàíèþ MRU - â âîñåìü ðàç ÷àùå, ÷åì ïðè âñåõ îñòàëüíûõ âàðèàíòàõ. Ôóíêöèîíàëüíî àêòèâíàÿ (ëàêòèðóþùàÿ) æåëåçà îáðàçîâàíà äîëüêàìè, ñîñòîÿùèìè èç àëüâåîë, ìåæäó êîòîðûìè â ðûõëîé âîëîêíèñòîé ñîåäèíèòåëüíîé òêàíè ðàñïîëàãàþòñÿ âíóòðèäîëüêîâûå ïðîòîêè è æèðîâûå êëåòêè. Ñóùåñòâóåò òðè ñóáïîïóëÿöèè, ïðåäïîëîæèòåëüíî ïðîèñõîäÿùèå îò åäèíîãî ïðåäøåñòâåííèêà (ñòâîëîâîé êëåòêè ýïèòåëèÿ ìîëî÷íîé æåëåçû) - ìèîýïèòåëèîöèòû, ýïèòåëèé ïðîòîêîâ ÌÆ è àëüâåîëÿðíûé æåëåçèñòûé ýïèòåëèé. Ðàíåå áûëî ïîêàçàíî ïðèñóòñòâèå ó÷àñòêîâ òêàíè ÌÆ áîãàòûõ êëåòêàìè-ïðåäøåñòâåííèêàìè êàê äëÿ ìûøåé [3], òàê è äëÿ ÷åëîâåêà [4, 5]. Äëÿ ïîñëåäóþùåé õàðàêòåðèñòèêè âûÿâëåííîé ïîïóëÿöèè îíà áûëà èññëåäîâàíà íà ýêñïðåññèþ ñïåöèôè÷åñêèõ ìàðê¸ðîâ òêàíè æåëåçû - ÑÊ14 - ìèîýïèòåëèàëüíûé ìàðêåð è ÑÊ18 - áåëîê, õàðàêòåðíûé äëÿ ýïèòåëèÿ ïðîñâåòà ïðîòîêà ÌÆ. Îêàçàëîñü, ÷òî ïðàêòè÷åñêè âñå Lin-/CD29hi/CD24+ íåñóò CÊ18, â òî âðåìÿ êàê CÊ14 ïîÿâëÿåòñÿ ëèøü íà åäèíè÷íûõ êëåòêàõ, ÷àñòî ñîâìåñòíî ëîêàëèçóÿñü ñ ÑÊ18. Äëÿ ïðîâåðêè ñïîñîáíîñòè èññëåäóåìûõ êëåòîê ê äèôôåðåíöèðîâêå áûëè ïðîâåäåíû îïûòû â Ìàòðèãåëå è ëàêòîãåííîé ñðåäå.  85% ñëó÷àåâ ôîðìèðîâàëèñü àëüâåîëÿðíî-ïîäîáíûå ñòðóêòóðû, êëåòêè êîòîðûõ ñåêðåòèðîâàëè áåëêè ìîëîêà. Äëÿ ïîäòâåðæäåíèÿ ãèïîòåçû «åäèíîãî ïðåäøåñòâåííèêà» ìå÷åíûå Lin-/CD29hi/CD24+ êëåòêè áûëè ðàçâåäåíû äëÿ èíúåêöèè èç ðàñ÷åòà «îäíà êëåòêà íà èíúåêöèþ».  8 ñëó÷àÿõ èç 68 áûëè ïîëó÷åíû LacZ+ ýïèòåëèàëüíûå îáðàçîâàíèÿ. Ãèñòîõèìè÷åñêîå èññëåäîâàíèå òàêèõ îáðàçîâàíèé âûÿâèëî íîðìàëüíóþ ìîðôîëîãèþ ïðîòîêîâ è èõ ñòàíäàðòíûé êëåòî÷íûé ñîñòàâ. Ôóíêöèîíèðîâàíèå òàêèõ íîâîîáðàçîâàííûõ åäèíèö ó áåðåìåííûõ îñîáåé íå îòëè÷àëîñü îò îñòàëüíîé (ñâîåé) òêàíè æåëåçû - â ïðîñâåòå ïðîòîêîâ âûÿâëÿëèñü ëèïèäíûå êàïëè è àãðåãàòû áåëêîâ ìîëîêà. Ñïîñîáíîñòü ê ñàìîîáíîâëåíèþ áûëà ïîäòâåðæäåíà îïûòàìè ñ ïîñëåäîâàòåëüíûìè ïåðåñàäêàìè îäíîé è òîé æå ïîïóëÿöèè. Òàêèì îáðàçîì, èñòèííîé ÑÊÌÆ àâòîðû ðàáîòû íàçûâàþò êëîíîãåííóþ ñàìîîáíîâëÿþùóþñÿ, ìóëüòèïîòåíòíóþ êëåòêó ñ Lin-/CD29hi/CD24+ ôåíîòèïîì.  ñâÿçè ñ ðàçâèòèåì ãèïîòåçû âîçìîæíîãî ó÷àñòèÿ âçðîñëûõ ñòâîëîâûõ êëåòîê â êàíöåðîãåíåçå áûëè ïðîâåäåíû ýêñïåðèìåíòû ïî ýêñïðåññèè CD24 è CD29 ãèïåðïëàçèðîâàííûìè, íî åùå íå çëîêà÷åñòâåííûìè êëåòêàìè ìûøåé äâóõ ìóòàíòíûõ ëèíèé.  ðåçóëüòàòå îêàçàëîñü, ÷òî Êëåòî÷íàÿ òðàíñïëàíòîëîãèÿ è òêàíåâàÿ èíæåíåðèÿ ¹ 1 (3), 2006 22 Íîâîñòè êëåòî÷íûõ òåõíîëîãèé àáñîëþòíîå êîëè÷åñòâî ÑÊÌÆ â ëèíèè ìûøåé, ìóòàíòíîé ïî Wnt-1, âîçðàñòàåò â øåñòü ðàç ïî ñðàâíåíèþ ñ äèêèì òèïîì, ÷òî óêàçûâàåò íà èõ âîçìîæíîå ó÷àñòèå â ðàçâèòèè ðàêà ÌÆ. Àâòîðû óêàçûâàþò íà ó÷àñòèå Wnt-1 ñèãíàëüíîãî ïóòè ïåðåðîæäåíèÿ â òàêèõ êëåòêàõ. Çäåñü èìååòñÿ àíàëîãèÿ ñ ãåìîïîýòè÷åñêèìè êëåòêàìè, ãäå Wnt-ïóòü òàêæå îòâå÷àåò çà ñàìîîáíîâëåíèèå [6]. Ýòè äàííûå ìîãóò óêàçûâàòü íà òî, ÷òî Wnt-1-îíêîãåí ìîæåò äàâàòü íà÷àëî ãåòåðîãåííûì îïóõîëÿì, çàòðàãèâàÿ íå òîëüêî ïóë ÑÊÌÆ, ò.å. ýòîò ïóòü ìîæåò áûòü óíèâåðñàëüíûì äëÿ êàíöåðîãåíåçà èç âçðîñëûõ ñòâîëîâûõ êëåòîê [7]. Îäíàêî, ïî ðåçóëüòàòàì ýêñïåðèìåíòîâ ñ äðóãîé ëèíèåé ìûøåé, MMTV-neu (ôîðìèðóþò ýïèòåëèàëüíûå îïóõîëè â ïðîñâåòå ïðîòîêà ÌÆ), íå áûëî îòìå÷åíî çíà÷èòåëüíîãî óâåëè÷åíèÿ êîëè÷åñòâà Lin-/CD29hi/ CD24+ êëåòîê, ÷òî ñâèäåòåëüñòâóåò â ïîëüçó òîãî, ÷òî ó êàæäîãî îíêîãåíà (wnt-1, neu) â òêàíè ìîëî÷íîé æåëåçû èìååòñÿ êàê ìèíèìóì îäèí òèï êëåòîê-ìèøåíåé, ïîäâåðãàþùèõñÿ çëîêà÷åñòâåííîìó ïåðåðîæäåíèþ. Ãëàâíûé ðåçóëüòàò ðàáîòû - èäåíòèôèêàöèÿ è âûäåëåíèå êëåòîê-ïðåäøåñòâåííèêîâ èç òêàíè ìîëî÷íîé æåëåçû è äîêàçàòåëüñòâî ôîðìèðîâàíèÿ ôóíêöèîíàëüíî àêòèâíîé ËÈÒÅÐÀÒÓÐÀ: 1. Kordon E.C., Smith G.H. An entire functional mammary gland may comprise the progeny from a single cell. Development 1998; 125: 1921-30. 2. Al-Hajj M., Wicha M.S., Benito-Hernandez A. et al. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 2003; 100; 3983-8. 3. Alvi A.J., Clayton H., Joshi C. et al. Functional and molecular characterisation of mammary side population cells. Breast. Cancer. Res. 2003; 5: R1R8. 4. Gudjonsson T., Villadsen R., Nielsen H.L. et al. Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties. Genes Dev. 2002; 16: 693-706. òêàíåâîé åäèíèöû èç åäèíñòâåííîé êëåòêè. Èíòåðåñíî, ÷òî ïî÷òè â îäíî è òî æå âðåìÿ â ýëåêòðîííîé âåðñèè Nature äðóãàÿ ãðóïïà èññëåäîâàòåëåé, ïðîâîäèâøàÿ ïîõîæèå ýêñïåðèìåíòû, îïèñûâàåò ñóùåñòâîâàíèå îñîáîé ïîïóëÿöèè ìóëüòèïîòåíòíûõ êëåòîê, òàêæå ñïîñîáíûõ ôîðìèðîâàòü íîðìàëüíóþ ýïèòåëèàëüíóþ òêàíü ÌÆ in vivo, íî â òå÷åíèå 6 íåäåëü.  ðàáîòå òàêæå ïðîàíàëèçèðîâàí êëåòî÷íûé öèêë òàêîãî ïóëà, õàðàêòåðèçóþùåãîñÿ âûñîêîé ýêñïðåññèåé CD24 è CD49f [8]. Òàêèì îáðàçîì, âñå ïîëó÷åííûå íà ñåãîäíÿøíèé äåíü ôàêòû ïîäòâåðæäàþò ñóùåñòâîâàíèå èñòèííûõ ñòâîëîâûõ êëåòîê âçðîñëîãî îðãàíèçìà â ÌÆ è èõ ó÷àñòèå â íîðìàëüíûõ è ïàòîëîãè÷åñêèõ ïðîöåññàõ. Åñëè àíàëîãè÷íûå ðåçóëüòàòû áóäóò ïîëó÷åíû è ó ÷åëîâåêà, òî çíà÷åíèå ýòèõ ðàáîò ìîæåò áûòü îãðîìíî. Ðåçóëüòàòû èññëåäîâàíèé ïîçâîëÿò èçó÷àòü ïðèðîäó ðàêà ìîëî÷íîé æåëåçû è èäåíòèôèöèðîâàòü íîâûå ìèøåíè äëÿ åãî ëå÷åíèÿ. Êðîìå òîãî, âîçìîæíîñòü ïîëó÷åíèÿ ôóíêöèîíèðóþùåé òêàíè æåëåçû èç îïðåäåë¸ííîé ãðóïïû êëåòîê ïîçâîëèò øèðîêî âíåäðèòü ìåòîä áèîëîãè÷åñêîãî àóòîïðîòåçèðîâàíèÿ ÌÆ ïîñëå ìàñòýêòîìèé èëè äëÿ ýñòåòè÷åñêîé ðåêîíñòðóêöèè. 5. Dontu G., Abdallah W.M., Foley J.M. et al. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 2003; 17: 1253-70. 6. Reya T., Duncan A.W., Ailles L. et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 2003; 423: 409-14. 7. Liu B.Y., McDermott S.P., Khwaja S.S., Alexander C.M. The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells. Proc. Natl. Acad. Sci. USA 2004; 101: 4158-63. 8. Stingl J., Eirew P., Ricketson I. et al. Purification and unique properties of mammary epithelial stem cells. Nature 2006 Jan 4; Epub. Ïîäãîòîâèëà Â.Ñ. Ìåëèõîâà Ïî ìàòåðèàëàì Nature 2006; 439: 84-88. doi:10.1038/nature04372 Ê âîïðîñó îá èììóíîãåííîñòè ýìáðèîíàëüíûõ ñòâîëîâûõ êëåòîê ÷åëîâåêà è èõ êîììèòèðîâàííûõ ïðîèçâîäíûõ Ýìáðèîíàëüíûå ñòâîëîâûå êëåòêè è èõ êîììèòèðîâàííûå ïðîèçâîäíûå (ÝÑÊ/ÊÏÝÑÊ) ÿâëÿþòñÿ îäíèì èç ïåðñïåêòèâíûõ âèäîâ êëåòî÷íîãî ìàòåðèàëà â òðàíñïëàíòàöèîííîé ðåãåíåðàòèâíîé ìåäèöèíå. Ìåòîäû ïîëó÷åíèÿ èçîãåííûõ «ïàöèåíò-ñïåöèôè÷åñêèõ» ëèíèé ÝÑÊ ïðèíöèïèàëüíî ñïîñîáíû ðåøèòü ïðîáëåìó äåôèöèòà äîíîðñêîãî ìàòåðèàëà (ÿéöåêëåòêè, áëàñòîöèñòû), òåì íå ìåíåå, ñàìè òåõíîëîãèè ïåðåíîñà ÿäðà èëè ñëèÿíèÿ íóæäàþòñÿ â çíà÷èòåëüíîì óñîâåðøåíñòâîâàíèè. Àëëîãåííûå ÝÑÊ ìîãóò áûòü ïîëó÷åíû â áîëüøîì êîëè÷åñòâå, îäíàêî èõ èñïîëüçîâàíèå îãðàíè÷åíî ñóùåñòâîâàíèåì èììóíîëîãè÷åñêîãî áàðüåðà, ïðåïÿòñòâóþùåãî ïðèæèâëåíèþ ëþáûõ íåñîâìåñòèìûõ êëåòîê è òêàíåé. Íåñìîòðÿ íà ýòî, ðÿä èññëåäîâàòåëåé ïðèäåðæèâàåòñÿ òî÷êè çðåíèÿ î íåêîòîðîé èììóíîïðèâèëåãèðîâàííîñòè ÝÑÊ/ÊÏÝÑÊ, óêàçûâàÿ, ÷òî ýòè êëåòêè íå ñïîñîáíû èíäóöèðîâàòü çíà÷èòåëüíóþ ðåàêöèþ îòòîðæåíèÿ ïðè àëëîãåííîé òðàíñïëàíòàöèè. Ýòè ïðåäñòàâëåíèÿ îñíîâûâàþòñÿ íà ðÿäå èçâåñòíûõ ôàêòîâ: • èìïëàíòèðîâàâøàÿñÿ â ìàòêó áëàñòîöèñòà (íåñóùàÿ ÝÑÊ), íåñìîòðÿ íà îòñóòñòâèå ïëàöåíòàðíîãî áàðüåðà íå ïîäâåðãàåòñÿ èììóííîìó îòòîðæåíèþ, õîòÿ è ýêñïðåññèðóåò íåñîâìåñòèìûå àíòèãåíû îòöà; Êëåòî÷íàÿ òðàíñïëàíòîëîãèÿ è òêàíåâàÿ èíæåíåðèÿ ¹ 1 (3), 2006 • ÝÑÊ/ÊÏÝÑÊ èìåþò íèçêèé óðîâåíü ýêñïðåññèè ìîëåêóë MHC I êëàññà, íå ýêñïðåññèðóþò ìîëåêóëû MHC II êëàññà è êîñòèìóëèðóþùèå ìîëåêóëû CD80, CD86 [1, 2]; • ÝÑÊ/ÊÏÝÑÊ ñóùåñòâåííî èíãèáèðóþò ïðîëèôåðàöèþ Òëèìôîöèòîâ â ðåàêöèè ñìåøàííîé êóëüòóðû ëèìôîöèòîâ [1]. Ýêñïåðèìåíòàëüíîå ïîäòâåðæäåíèå íèçêîé èììóíîãåííîñòè ÝÑÊ/ÊÏÝÑÊ in vivo èìååò âàæíîå ïðàêòè÷åñêîå çíà÷åíèå, ïîñêîëüêó îòêðûâàåò ðåàëüíûå ïåðñïåêòèâû ïîëó÷åíèÿ íåîãðàíè÷åííîãî ðåñóðñà ýìáðèîíàëüíûõ è êîììèòèðîâàííûõ êëåòîê äëÿ òðàíñïëàíòàöèè. Îäíèì èç ïåðâûõ èññëåäîâàíèé, ïîñâÿùåííûõ äàííîé ïðîáëåìå, ÿâëÿåòñÿ íåäàâíî îïóáëèêîâàííàÿ â îíëàéí-âåðñèè æóðíàëà Stem Cells ðàáîòà ãðóïïû Ì. Drukker.  èññëåäîâàíèè èñïîëüçîâàëèñü ðàäèàöèîííûå õèìåðû «Trimera», ÿâëÿþùèåñÿ ýêñïåðèìåíòàëüíîé ìîäåëüþ èììóííîé ñèñòåìû ÷åëîâåêà äëÿ èçó÷åíèÿ «ðåàêöèè õîçÿèí ïðîòèâ òðàíñïëàíòàòà» (ðèñ.) [3,4]. Ââåäåíèå 1 ìèëëèîíà ÝÑÊ ÷åëîâåêà èëè íèçêîäèôôåðåíöèðîâàííûõ òêàíåâûõ ôðàãìåíòîâ, âûäåëåííûõ èç 4-íåäåëüíûõ ÝÑÊ-èíäóöèðîâàííûõ òåðàòîì, âûïîëíÿëîñü ïîä ïî÷å÷íóþ êàïñóëó ìûøàì-õèìåðàì.  êà÷åñòâå êîíòðîëÿ îñóùåñòâëÿëàñü òðàíñïëàíòàöèÿ