15 Íîâîñòè êëåòî÷íûõ òåõíîëîãèé ïîëó÷èâøèõ òðàíñïëàíòàòû îò äîíîðîâ ïðîòèâîïîëîæíîãî ïîëà [8, 9, 11]. Áîëåå òîãî, Harris ïîêàçàë äèôôåðåíöèðîâêó ñòâîëîâûõ êëåòîê, ïîëó÷åííûõ èç êîñòíîãî ìîçãà, â ë¸ãî÷íûé ýïèòåëèé áåç ñëèÿíèÿ in vivo [13]. Àâòîðû ñòàòüè ïðîòåñòèðîâàëè îáðàçöû òêàíåé íà ïîëèïëîèäèþ ñîïóòñòâóþùåé äåìîíñòðàöèåé Õ- è Y-õðîìîñîì. È õîòÿ êëåòîê ñ àíîìàëüíûì õðîìîñîìíûì íàáîðîì îáíàðóæåíî íå áûëî, èññëåäîâàòåëè ñ÷èòàþò, ÷òî èç-çà ïðèðîäû ìàòåðèàëà âîçìîæíî áûëî ïðîâåñòè èñ÷åðïûâàþùèé òåñò íà ïîëèïëîèäèþ. Òàêèì îáðàçîì, â ðàáîòå ïîêàçàíî, ÷òî êëåòêè, ìèãðèðîâàâøèå â ë¸ãêèå èç âíåëåãî÷íîãî èñòî÷íèêà (â ÷àñòíîñòè êîñòíîãî ìîçãà), ñïîñîáíû ê ýíãðàôòèíãó è äèôôåðåíöèðîâêå â êëåòêè àëüâåîëÿðíîãî ýïèòåëèÿ, à òàêæå â êëåòêè ìåçåíõèìàëüíîãî ïðîèñõîæäåíèÿ, âêëþ÷àÿ ìàêðîôàãè, ýíäîòåëèé è ãëàäêèå ìèîöèòû. Ðàáîòà ïîäòâåðæäàåò, ÷òî òàêîé ìåõàíèçì ðåïàðàòèâíîé ðåãåíåðàöèè âîçìîæåí â ë¸ãêèõ ÷åëîâåêà. ËÈÒÅÐÀÒÓÐÀ: 1. Jiang Y., Jahagirdar B.N., Reinhardt R.L. et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418: 41-9. 2. Kotton D.N., Ma B.Y., Cardoso W.V. et al. Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development 2001; 128: 5181-8. 3. Okamoto R., Yajima T., Yamazaki M. et al. Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract. Nat. Med. 2002; 8: 1011-7. 4. Ying Q.L., Nichols J., Evans E.P., Smith A.G. Changing potency by spontaneous fusion. Nature 2002; 416: 545-8. 5. Krause D.S., Theise N.D., Collector M.I. et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cells. Cell 2001; 105: 369-77. 6. Theise N.D., Henegariu O., Grove J. et al. Radiation pneumonitis in mice: A severe injury model for pneumocyte engraftment from bone marrow. Exp. Haematol. 2002; 30: 1333-8. 7. Davies J.C., Potter M., Bush A. et al. Bone marrow stem cells do not repopulate the healthy upper respiratory tract. Pediatr. Pulmonol. 2002; 34: 251-6. Ïîäîáíûå ðàáîòû ìîãóò óêàçàòü íà íîâûå èíòåðåñíûå âîçìîæíîñòè äëÿ ëå÷åíèÿ çàáîëåâàíèé ë¸ãêèõ. Êëåòêè, ïðèõîäÿùèå â ë¸ãêîå ïðè åãî ïîâðåæäåíèè, ïðåäñòàâëÿþò ñîáîé ïîòåíöèàëüíî óïðàâëÿåìóþ ñèñòåìó, êîòîðàÿ ìîæåò èñïîëüçîâàòüñÿ äëÿ óñêîðåíèÿ âîññòàíîâëåíèÿ ýïèòåëèÿ ëåãêèõ.  äîïîëíåíèå ê ýòîìó, âîçìîæíî, ðåïîïóëÿöèÿ ïîâðåæä¸ííûõ äûõàòåëüíûõ ïóòåé íîðìàëüíûìè êëåòêàìè ìîæåò áûòü äîñòèãíóòà ïðè òðàíñïëàíòàöèè êîñòíîãî ìîçãà, êàê áûëî ïîêàçàíî äðóãèìè àâòîðàìè ïðè ëå÷åíèè ìóêîâèñöèäîçà [8]. Àâòîðû òàêæå ïðåäïîëàãàþò, ÷òî òðàíñïëàíòàöèÿ êîñòíîãî ìîçãà ìîæåò áûòü èñïîëüçîâàíà â êà÷åñòâå äîïîëíèòåëüíîãî òåðàïåâòè÷åñêîãî ñðåäñòâà ïðè ïðèìåíåíèè ãåííîé òåðàïèè. Ýòà âîçìîæíîñòü áûëà èññëåäîâàíà íà ýêñïåðèìåíòàëüíîé ìîäåëè è áûëî ïîêàçàíî, ÷òî ñòâîëîâûå êëåòêè êîñòíîãî ìîçãà ìîãóò áûòü òðàíñôîðìèðîâàíû in vitro, à çàòåì, ïîñëå èìïëàíòàöèè, äèôôåðåíöèðîâàòüñÿ â äûõàòåëüíûé ýïèòåëèé ïðàêòè÷åñêè áåç ïîòåðü ýêñïðåññèè òðàíñãåíîâ [14]. 8. Suratt B.T., Cool C.D., Serls A.E. et al. Human pulmonary chimerism after hematopoietic stem cell transplantation. Am. J. Respir. Crit. Care. Med. 2003; 168: 318-22. 9. Mattsson J., Jansson M., Wernerson A., Hassan M. Lung epithelial cells and type II pneumocytes of donor origin after allogeneic hematopoietic stem cell transplantation. Transplantation 2004; 78: 154-7. 10. Spees J.L., Olson S.D., Ylostalo J. et al. Differentiation, cell fusion and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proc. Natl. Acad. Sci. USA 2003; 100: 2397-402. 11. Kleeberger W., Versmold A., Rothamel T. et al. Increased chimerism of bronchial and alveolar epithelium in human lung allografts undergoing chronic injury. Am. J. Pathol. 2003; 162: 1487-9. 12. Vassilopoulos G., Wang P.R., Russell D.W. Transplanted bone marrow regenerates liver by cell fusion. Nature 2003; 422: 901-4. 13. Harris R.G., Herzog E.L., Brusca E.M. et al. Lack of a fusion requirement for development of bone marrow-derived epithelia. Science 2004; 305: 90-3. 14. Grove J.E., Lutzko C., Priller J. et al. Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium. Am. J. Respir. Cell Mol. Biol. 2002; 27: 645-51. Ïîäãîòîâèëà À.Ñ. Ãðèãîðÿí Ïî ìàòåðèàëàì Tissue Eng; 2005; 11: 1115 Ó÷àñòèå ñòâîëîâûõ êëåòîê âîëîñÿíîãî ôîëëèêóëà â çàæèâëåíèè êîæíûõ ðàí Èçâåñòíî, ÷òî êîæà è âîëîñû ìëåêîïèòàþùèõ õàðàêòåðèçóþòñÿ âûñîêîé ñêîðîñòüþ îáíîâëåíèÿ çà ñ÷¸ò ïðîëèôåðàöèè è äèôôåðåíöèðîâêè ïðîãåíèòîðíûõ êëåòîê. Ê ñòâîëîâûì êëåòêàì (ÑÊ) âîëîñÿíîãî ôîëëèêóëà (ÂÔ), îòâåòñòâåííûì ïðåæäå âñåãî çà ðîñò âîëîñà, îòíîñÿò 2 ïîïóëÿöèè, îäíà èç êîòîðûõ ðàñïîëîæåíà â äåðìàëüíîì ñîñî÷êå íèæíåé ÷àñòè ôîëëèêóëà, à äðóãàÿ - â áóãîðêå - bulge (ÁÂÔ), ëîêàëèçîâàííîì â âåðõíåé åãî ÷àñòè ïîä óñòüåì ñàëüíîé æåëåçû [1].  íîðìå èõ ïðîëèôåðàöèÿ è äèôôåðåíöèðîâêà îáóñëàâëèâàþò ôîðìèðîâàíèå âñåõ òèïîâ êëåòîê ÂÔ, ñàëüíîé è ïîòîâîé æåëåç. Áûëî ïîêàçàíî, ÷òî â ðåïàðàöèè ïîâðåæäåíèÿ êîæè ó÷àñòâóþò êàê áàçàëüíûå êëåòêè ýïèäåðìèñà, òàê è êëåòêè äåðìàëüíîãî ñîñî÷êà [2]. Ó÷àñòèå êëåòîê áóãîðêà ÂÔ â ðåãåíåðàöèè êîæè îñòà¸òñÿ íåèçó÷åííûì. Ãðóïïîé Cotsarelis èç University of Pennsylvania áûëî óñòàíîâëåíî, ÷òî ñïåöèôè÷íûì ìàðê¸ðîì ñòâîëîâûõ êëåòîê ÁÂÔ ÿâëÿåòñÿ âûñîêèé óðîâåíü ýêñïðåññèè áåëêà öèòîêåðàòèíà-15 [3]. Ðàíåå áûëî ïîêàçàíî, ÷òî ýòè êëåòêè êàê ìèíèìóì áèïîòåíòíû è ìèãðèðóþò â ýïèäåðìèñ ôèçèîëîãè÷åñêè è â ïðîöåññå ðåãåíåðàöèè [5, 7]. Ïîçäíåå âûÿñíèëîñü, ÷òî êëåòêè ÁÂÔ îáëàäàþò ñâîéñòâàìè êëîíîãåííîñòè è ìóëüòèïîòåíòíû. Ïðè òðàíñïëàíòàöèè ïîñëå 140 óäâîåíèé â êóëüòóðå îíè äàâàëè íà÷àëî âñåì ëèíèÿì êëåòîê, ó÷àñòâóþùèì â ôîðìèðîâàíèè âîëîñà. Ìíîãî÷èñëåííûå ôîëëèêóëû áûëè ñôîðìèðîâàíû îò ïîòîìñòâà òîëüêî îäíîé ÑÊ [4]. Òàêèì îáðàçîì, ðàáîòû ðÿäà èññëåäîâàòåëüñêèõ ãðóïï äîêàçàëè, ÷òî êëåòêè îáëàñòè ÁÂÔ ÿâëÿþòñÿ èñòèííûìè ÑÊ âçðîñëîãî îðãàíèçìà ìëåêîïèòàþùèõ [1, 3-6]. Îòêðûòèå äîëãîæèâóùèõ ÑÊ â ýïèäåðìèñå è îáëàñòè ÁÂÔ, ïðèâåëî ê ïîÿâëåíèþ ãèïîòåçû î òîì, ÷òî, âîçìîæíî, ýòè êëåòêè ó÷àñòâóþò è â îáíîâëåíèè ýïèäåðìèñà â íîðìå, è ïðè çàæèâëåíèè êîæíûõ ðàí [1]. Äëÿ ïðîâåðêè ýòîé ãèïîòåçû ãðóïïà âî ãëàâå ñ George Cotsarelis ïðîèçâåëà «ãåííóþ àáëÿöèþ» ýòèõ êëåòîê, èñïîëüçóÿ èõ óíèêàëüíûé ìàðêåð - öèòîêåðàòèí-15.  ðåçóëüòàòå ïîäîáíîé àáëÿöèè ðîñò âîëîñ ïðåêðàùàëñÿ ïî ïðè÷èíå ïîëíîé äåãðàäàöèè ôîëëèêóëîâ, îäíàêî ýïèäåðìèñ Êëåòî÷íàÿ òðàíñïëàíòîëîãèÿ è òêàíåâàÿ èíæåíåðèÿ ¹ 1 (3), 2006 16 Íîâîñòè êëåòî÷íûõ òåõíîëîãèé îñòàâàëñÿ íåïîâðåæäåííûì. Èòîãîì ýêñïåðèìåíòà ñëóæèò âûâîä î òîì, ÷òî ñòâîëîâûå êëåòêè ÂÔ è îáëàñòè áóãîðêà íå èãðàþò çíà÷èòåëüíîé ðîëè â ôóíêöèîíèðîâàíèè íåïîñðåäñòâåííî êëåòîê êîæè. Ýòè äàííûå ïîäòâåðæäàþò, ÷òî ýïè- Ñõåìà ñòðîåíèÿ âîëîñÿíîãî ôîëëèêóëà: ÁÂÔ áóãîðîê âîëîñÿíîãî ôîëëèêóëà ËÈÒÅÐÀÒÓÐÀ: 1. Cotsarelis G., Sun T.T., Lavker R.M. Label-retaining cells resident in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 1990; 61: 1329-37. 2. Morasso M.I., Tomic-Canic M. Epidermal Stem Cells: the cradle of epidermal determination, differentiation and wound healing. Biol. Cell 2005; 97: 173-83. 3. Liu Y., Lyle S., Yang Z., Cotsarelis G. Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge. J. Invest. Dermatol. 2003; 121: 963-8. 4. Claudinot S., Nicolas M., Oshima H. Et al. Long-term renewal of hair follicles from clonogenic multipotent stem cells. Proc. Natl. Acad. Sci. USA 2005; 102(41): 14677-82. òåëèé êîæè èìååò ñîáñòâåííûé íåçàâèñèìûé èñòî÷íèê ñòâîëîâûõ ýëåìåíòîâ êëåòêè, ðàñïîëîæåííûå â áàçàëüíîì ñëîå ýïèäåðìèñà, ó÷àñòâóþùèå â îáðàçîâàíèè òàê íàçûâàåìîé ýïèäåðìàëüíîé ïðîëèôåðàòèâíîé åäèíèöû (ÝÏÅ) [8]. Äàëüíåéøèå ýêñïåðèìåíòû ãðóïïû G. Cotsarelis ïîêàçàëè, ÷òî ïîñëå ïîâðåæäåíèÿ ýïèäåðìèñà êëåòêè èç îáëàñòè ÁÂÔ (êîòîðûå ïðèíÿòî îòíîñèòü ê ñòâîëîâûì êëåòêàì âîëîñà) ìèãðèðóþò â îáëàñòü äåôåêòà, ïðèîáðåòàÿ ýïèäåðìàëüíûé ôåíîòèï. Îäíàêî, èññëåäîâàòåëè íå îáíàðóæèâàëè èõ â ðàíå ÷åðåç íåñêîëüêî íåäåëü. Ýòî ãîâîðèò î òîì, ÷òî îíè îòâå÷àþò çà ïåðâûé - ñðî÷íûé - îòâåò íà ïîâðåæäåíèå, ôîðìèðóÿ áûñòðî äåëÿùóþñÿ è âïîñëåäñòâèè äèôôåðåíöèðóþùóþñÿ êîðîòêî æèâóùóþ ïîïóëÿöèþ. Òàêèì îáðàçîì, ñòâîëîâûå êëåòêè îáëàñòè ÁÂÔ îòâå÷àþò çà áûñòðóþ ðåýïèòàëèçàöèþ ðàíû, äàâàÿ êîðîòêî æèâóùóþ, ïåðåõîäíóþ, àêòèâíî äåëÿùóþñÿ è ìèãðèðóþùóþ ïîïóëÿöèþ. Cèãíàëû, ïîñòóïàþùèå èç äåðìàëüíîãî ñîñî÷êà â áóãîðîê è çàïóñêàþùèå ðåãåíåðàòèâíûå ïðîöåññû (Wnt/beta-catenin), óæå âûÿâëåíû è èçó÷åíû [9]. Îäíàêî ìîëåêóëû, çàïóñêàþùèå áûñòðûé îòâåò êëåòîê ÁÂÔ íà ïîâðåæäåíèå êîæíîãî ýïèòåëèÿ, äî ñèõ ïîð íå ÿñíû. Èäåíòèôèêàöèÿ òàêèõ ñèãíàëüíûõ ìîëåêóë ïîçâîëèò ðàçðàáîòàòü ñïîñîáû áîðüáû ñ ãëóáîêèìè ïîâðåæäåíèÿìè êîæè è äðóãèìè íàðóøåíèÿìè, íàïðèìåð, ñ âîçðàñòíîé ýïèäåðìàëüíîé àòðîôèåé. Öåííîñòü ðàáîòû ñîñòîèò â ôóíêöèîíàëüíîì ðàçäåëåíèè äâóõ ãðóïï ñòâîëîâûõ êëåòîê - ýïèäåðìèñà è ÁÂÔ, à, çíà÷èò, è â èõ áîëåå îñîçíàííîì è öåëåíàïðàâëåííîì èñïîëüçîâàíèè â êà÷åñòâå êëåòîê-ïåðåíîñ÷èêîâ òåðàïåâòè÷åñêèõ ãåíîâ â çàáîëåâàíèÿõ âîëîñ è êîæè (îòäåëüíî).  ïðàêòè÷åñêîì îòíîøåíèè ðàáîòà ìîæåò âíåñòè è íåêîòîðûé âêëàä â êîñìåòîëîãèþ - ïðè ëàçåðíîì óäàëåíèè íåæåëàòåëüíûõ âîëîñ ïðîèñõîäèò àáëÿöèÿ òîëüêî êëåòîê ôîëëèêóëà, à öåëîñòíîñòü ýïèäåðìèñà â çíà÷èòåëüíîé ñòåïåíè íå èçìåíÿåòñÿ. Êðîìå òîãî, óíèêàëüíûå ñâîéñòâà 2 íåçàâèñèìûõ ñòâîëîâûõ ïîïóëÿöèé âîëîñà ìîæíî áóäåò èñïîëüçîâàòü äëÿ ëå÷åíèÿ àëîïåöèè è êîæíûõ ðàí. 5. Taylor G., Lehrer M.S., Jensen P.J. et al. Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 2000; 102(4): 451-61. 6. Morris R.J., Liu Y., Marles L. et al. Capturing and profiling adult hair follicle stem cells. Nat. Biotechnol. 2004; 22(4): 411-7 7. Tumbar T., Guasch G., Greco V. et al. Defining the epithelial stem cell niche in skin. Science 2004; 303(5656): 359-63. 8. Ãðàôîâà Ã.ß. Öèòîàðõèòåêòîíèêà ýïèäåðìèñà è ýïèäåðìàëüíîïðîëèôåðàòèâíûå åäèíèöû (ÝÏÅ). Àðõèâ àíàò., ãèòîëîãèè è ýìáðèîë. 1982; 82(4): 73-85. 9. Van Mater D., Kolligs F.T., Dlugosz A.A., Fearon E.R. Transient activation of beta-catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice. Genes Dev. 2003; 17: 1219-24. Ïîäãîòîâèëà Â.Ñ. Ìåëèõîâà Ïî ìàòåðèàëàì Nat. Med. 2005; 11: 1351-4 Êëåòî÷íàÿ òðàíñïëàíòîëîãèÿ è òêàíåâàÿ èíæåíåðèÿ ¹ 1 (3), 2006