HUMAN STUDY Восстановление слизистой оболочки полости

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Íîâîñòè êëåòî÷íûõ òåõíîëîãèé
ËÈÒÅÐÀÒÓÐÀ:
1. Folkman J., Hochberg M. Self-regulation of growth in three dimensions.
J. Exp. Med. 1973; 138: 745-53.
2. Polykandriotis E., Arkudas A., Horch R. et al. Autonomously vascularized
cellular constructs in tissue engineering: opening a new perspective for biomedical
science. J. Cell Mol. Med. 2007; 11(1): 6-20.
3. Arkudas A., Tjiawi J., Bleiziffer O. et al. Fibrin gel-immobilized VEGF and
bFGF efficiently stimulate Angiogenesis in the AV Loop Model. Mol. Med. 2007;
13(9-10): 480-7.
4. Ahrendt G, Chickering D., Ranieri J. Angiogenic growth factors: a review
for tissue engineering. Tissue Eng. 1998; 2: 117-30.
5. Khouri R., Upton J., Shaw W. Prefabrication of composite free flaps
through staged microvascular transfer: an experimental and clinical study. Plast.
Reconstr. Surg. 1991; 87: 108-15.
6. Lokmic Z., Stillaert F., Morrison W. et al. An arteriovenous loop in a
protected space generates a permanent, highly vascular, tissue-engineered
construct. FASEB J. 2007; 21(2): 511-22.
7. Arkudas A., Beier J., Heidner K. et al. Axial prevascularization of porous
matrices by an arteriovenous loop promotes survival and differentiation of
transplanted autologous osteoblasts. Tissue Eng. 2007; 13(7): 1549-60.
8. Kneser U., Polykandriotis E., Ohnolz J. et al. Engineering of vascularized
transplantable bone tissues: induction of axial vascularization in an osteoconductive
matrix using an arteriovenous loop. Tissue Eng. 2006; 12: 1721-31.
9. Kuznetsov S.A., Robey P.G. A look at the history of bone marrow stromal
cells. Graft. 2000; 3(6): 278-83.
10. Casabona F., Martin I., Muraglia A. et al. Prefabricated engineered bone
flaps: an experimental model of tissue reconstruction in plastic surgery. Plast
Reconstr Surg. 1998; 101(3): 577-81.
Ïîäãîòîâèë È.ß. Áîçî
Ïî ìàòåðèàëàì: Arkudas A., Beier J., Heidner K. et al. Axial prevascularization of porous matrices by an arteriovenous loop
promotes survival and differentiation of transplanted autologous osteoblasts. Tissue Eng. 2007; 13(7): 1549-60
HUMAN STUDY
Âîññòàíîâëåíèå ñëèçèñòîé îáîëî÷êè ïîëîñòè ðòà
ïóòåì òðàíñïëàíòàöèè àóòîãåííûõ êåðàòèíîöèòîâ:
êëèíè÷åñêîå èññëåäîâàíèå
Êîìïëåêñ çàáîëåâàíèé ñëèçèñòîé îáîëî÷êè ïîëîñòè
ðòà èíîãäà òðåáóåò ïðèìåíåíèÿ àêòèâíîé õèðóðãè÷åñêîé
òàêòèêè. Ñîñòîÿíèÿ ïîñëå ðåçåêöèè ëåéêîïëàêèè, ïëîñêîêëåòî÷íîãî ðàêà, à òàêæå àòðîôèè ñëèçèñòîé îáîëî÷êè
àëüâåîëÿðíîãî ãðåáíÿ, ñîïðîâîæäàþùèåñÿ ïîòåðåé èëè
ïîðàæåíèåì åå ó÷àñòêà íà ïëîùàäè áîëåå 1 ñì2, òðåáóþò
âîññòàíîâëåíèÿ äåôåêòà.  íàñòîÿùåå âðåìÿ õèðóðãè÷åñêàÿ òàêòèêà ñâîäèòñÿ ê ïåðåìåùåíèþ ñâîáîäíûõ ëîñêóòîâ.
Îäíàêî íå âñåãäà îïåðàöèÿ ìîæåò áûòü óñïåøíà. Ýòî ñëó÷àåòñÿ ëèáî â ñâÿçè ñ ðàçâèòèåì îñëîæíåíèé (íåêðîç
òðàíñïëàíòàòà), èëè êîãäà äåôåêò íå ïîçâîëÿåò âûïîëíèòü
îïåðàòèâíîå âìåøàòåëüñòâî, íå íàíåñÿ óùåðá òêàíÿì â
ìåñòå çàáîðà [1, 2]. Àëüòåðíàòèâîé àóòîòðàíñïëàíòàöèè
èëè ïëàñòèêè ñëèçèñòîé îáîëî÷êè ìîãóò áûòü èìïëàíòàöèè
áèîëîãè÷åñêè àêòèâíûõ ìàòåðèàëîâ â çîíó äåôåêòà ñ ïîñëåäóþùèì îæèäàíèåì ýïèòåëèçàöèè ñêàôôîëäà ñ êðàåâûõ çîí ðàíû.  êëèíè÷åñêîé ïðàêòèêå ñòîìàòîëîãîâ, äåðìàòîëîãîâ è õèðóðãîâ â ÑØÀ øèðîêî èñïîëüçóåòñÿ
äåöåëëþëèðîâàííàÿ, ñïåöèàëüíî î÷èùåííàÿ îò àíòèãåíîâ,
÷åëîâå÷åñêàÿ äåðìà AlloDerm, êîòîðàÿ ïðåäíàçíà÷åíà äëÿ
ñòèìóëÿöèè ïðîöåññîâ çàæèâëåíèÿ ñëèçèñòûõ îáîëî÷åê è
êîæè [3, 4]. Êðîìå òîãî, ïîìèìî ñêàôôîëäîâ äëÿ âîññòàíîâëåíèÿ êîæè â øèðîêóþ ïðàêòèêó áûëè âíåäðåíû è êëåòî÷íûå
àëëîòðàíñïëàíòàòû, ÿðêèì ïðèìåðîì êîòîðûõ ìîæåò ñëóæèòü Apligraf. ßâëÿÿñü æèâûìè ýêâèâàëåíòàìè êîæè, îíè
çàðåêîìåíäîâàëè ñåáÿ õîðîøî êàê â ýñòåòè÷åñêîé ìåäèöèíå, òàê è â êîìáóñòèîëîãèè [5, 6]. Èñïîëüçîâàíèå êëåòî÷íûõ òåõíîëîãèé â õèðóðãè÷åñêîé ñòîìàòîëîãèè êàæåòñÿ
ñàìî ñîáîé ðàçóìåþùèìñÿ äåëîì.
Êëåòî÷íàÿ òðàíñïëàíòîëîãèÿ è òêàíåâàÿ èíæåíåðèÿ Òîì II, ¹ 4, 2007
Èññëåäîâàòåëüñêàÿ ãðóïïà Óíèâåðñèòåòà Êîáý (ßïîíèÿ)
ïðîäåìîíñòðèðîâàëà âîçìîæíîñòü èñïîëüçîâàíèÿ àóòîòðàíñïëàíòàòîâ äëÿ âîññòàíîâëåíèÿ äåôåêòîâ ñëèçèñòîé îáîëî÷êè ïîëîñòè ðòà ó ïÿòíàäöàòè ïàöèåíòîâ ñ ëåéêîïëàêèåé,
ïëîñêîêëåòî÷íûì ðàêîì ïîëîñòè ðòà è àòðîôèåé ñëèçèñòîé
îáîëî÷êè â îáëàñòè àëüâåîëÿðíîãî ãðåáíÿ. Êëåòî÷íûé ìàòåðèàë ïîëó÷àëè ïóòåì áèîïñèè, êåðàòèíîöèòû âûäåëÿëè,
êóëüòèâèðîâàëè è íàíîñèëè íà AlloDerm. Ñðåäíèé ðàçìåð
äåôåêòîâ ñîñòàâëÿë ïîðÿäêà 6 ñì2. Ýïèòåëèçàöèÿ íàñòóïàëà â ñðåäíåì ÷åðåç 28 äíåé, ÷òî, ïî íàáëþäåíèÿì àâòîðîâ,
áûñòðåå è ýôôåêòèâíåå, ÷åì ïðîñòî èìïëàíòàöèÿ AlloDerm.
Êðîìå êëèíè÷åñêèõ äàííûõ ýôôåêòèâíîñòü ìåòîäà áûëà
ïîäòâåðæäåíà áèîïñèåé. Ðåçóëüòàòû ãèñòîëîãè÷åñêîãî èññëåäîâàíèÿ ïðîäåìîíñòðèðîâàëè íàëè÷èå ðàçâèòîãî ýïèòåëèàëüíîãî ñëîÿ ó ïàöèåíòîâ ïîñëå àóòîòðàíñïëàíòàöèè, òîãäà êàê ýïèòåëèàëüíîé âûñòèëêè íà ïîâåðõíîñòè áåñêëåòî÷íîé
ìàòðèöû AlloDerm âûÿâëåíî íå áûëî. Â êîíöå ñðîêà íàáëþäåíèÿ (1 ìåñ.) òàêæå áûëà âûÿâëåíà ìèíèìàëüíàÿ êîíòðàêòóðà ó
ïàöèåíòîâ ïîñëå àóòîòðàíñïëàíòàöèè.
Òàêèì îáðàçîì, äàííîå íàáëþäåíèå ñâèäåòåëüñòâóåò î êëèíè÷åñêîé ýôôåêòèâíîñòè ìåòîäà òðàíñïëàíòàöèè àóòîãåííûõ
êåðàòèíîöèòîâ íà áåñêëåòî÷íîé äåðìàëüíîé ìàòðèöå AlloDerm
â ñðàâíåíèè ñ èìïëàíòàöèåé òîé æå ìàòðèöû íîñèòåëÿ, íî
áåç êëåòîê. Îäíàêî â èññëåäîâàíèè îñòàëñÿ íåðàñêðûòûì
âîïðîñ: áåçîïàñíî ëè èñïîëüçîâàòü ïîäîáíûå êëåòî÷íûå
òðàíñïëàíòàòû ó îíêîëîãè÷åñêèõ ïàöèåíòîâ. Âíåäðåíèå â
êëèíè÷åñêóþ ïðàêòèêó äàííîãî ìåòîäà â ßïîíèè ñèëüíî îãðàíè÷åííî â ñâÿçè ñ îòñóòñòâèåì ðàçðåøåíèÿ íà èñïîëüçîâàíèå ìàòðèöû AlloDerm, î ÷åì è çàÿâèëè àâòîðû.
Íîâîñòè êëåòî÷íûõ òåõíîëîãèé
ËÈÒÅÐÀÒÓÐÀ:
1. Ëóöêàÿ È.Ê. Çàáîëåâàíèÿ ñëèçèñòîé îáîëî÷êè ïîëîñòè ðòà. Ì.: Ìåä.
ëèò.; 2006: 239-41.
2. Ïîæàðèöêàÿ Ì.Ì., Áî÷àðîâà Î.À., ×åêàëèíà Ò.Ë., Âîðîíèí Â.Ô., Êíÿæåâ
Â.À. Ñîâðåìåííûå àñïåêòû ïàòîãåíåçà è ëå÷åíèÿ ëåéêîïëàêèè ñëèçèñòîé
îáîëî÷êè ïîëîñòè ðòà. ÃÎÓ ÂÓÍÌÖ 2006: 31-3.
3. Falanga V, Saap L.J, Ozonoff A. Wound bed score and its correlation
with healing of chronic wounds. Dermatol. Ther. 2006; 19(6): 383-90.
4. Felipe M., Andrade P., Grisi M. et al. Comparison of two surgical
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procedures for use of the acellular dermal matrix graft in the treatment of gingival
recessions: a randomized controlled clinical study. J. Periodontol. 2007; 78(7):
1209-17.
5. Hotta T., Yokoo S., Terashi H., Komori T. Clinical and histopathological
analysis of healing process of intraoral reconstruction with ex vivo produced oral
mucosa equivalent. Kobe J. Med. Sci. 2007; 53(1-2): 1-14.
6. Pham C., Greenwood J., Cleland H., Woodruff P., Maddern G.
Bioengineered skin substitutes for the management of burns: A systematic review.
Burns. 2007; 33(8): 946-57.
Ïîäãîòîâèë À.Â. Âîëêîâ
Ïî ìàòåðèàëàì: Hotta T., Yokoo S., Terashi H., Komori T. Clinical and Histopathological Analysis of Healing Process of Intraoral
Reconstruction with ex vivo Produced Oral Mucosa Equivalent. Kobe J. Med. Sci. 2007; 53: 1-14
Òðàíñïëàíòàöèÿ ÌÌÑÊ æèðîâîé òêàíè êàê ñïîñîá áîðüáû
ñ ðåàêöèåé «òðàíñïëàíòàò ïðîòèâ õîçÿèíà» ó äåòåé
Îñíîâíîé ïðîáëåìîé ñîâðåìåííîé òðàíñïëàíòîëîãèè íàðÿäó ñî ñëîæíîñòüþ ïîäáîðà äîíîðà ÿâëÿåòñÿ ðàçâèòèå ðåàêöèè «òðàíñïëàíòàò ïðîòèâ õîçÿèíà» (ÐÒÏÕ) ïîñëå óñïåøíîé
òðàíñïëàíòàöèè. Äàííîå îñëîæíåíèå ìîæåò ïðèâåñòè ê òÿæåëûì îñëîæíåíèÿì è ñìåðòè ðåöèïèåíòà. Íà ñîâðåìåííîì
ýòàïå áîðüáû ñ ýòèì ñèíäðîìîì äîñòàòî÷íî ýôôåêòèâíî
èñïîëüçóþò öèòîñòàòèêè, ãëþêîêîðòèêîèäû, à òàê æå àíòèëåéêîöèòàðíóþ ñûâîðîòêó [1, 2]. Îäíàêî íå ó âñåõ ïàöèåíòîâ óäàåòñÿ äåðæàòü ðàçâèòèå äàííîãî îñëîæíåíèÿ ïîä êîíòðîëåì.
 ïîñëåäíåå âðåìÿ ñòàëî èçâåñòíî îá èììóíîìîäóëèðóþùåì äåéñòâèè ìóëüòèïîòåíòíûõ ìåçåíõèìàëüíûõ ñòðîìàëüíûõ êëåòîê (ÌÌÑÊ) êîñòíîãî ìîçãà ïîñëå òðàíñïëàíòàöèè èõ
ïàöèåíòàì ñ àóòîèììóííûìè çàáîëåâàíèÿìè [3, 5]. ÌÌÑÊ
æèðîâîé òêàíè è ôèáðîáëàñòîïîäîáíûå êëåòêè èç äðóãèõ
èñòî÷íèêîâ îêàçûâàþò ñõîäíîå äåéñòâèå íà èììóííûé ñòàòóñ îðãàíèçìà [4]. Èììóíîêîððåêöèÿ ìóëüòèïîòåííûìè
ñòðîìàëüíûìè êëåòêàìè íåêîñòíîìîçãîâîãî ïðîèñõîæäåíèÿ
äëÿ êîíòðîëÿ íàä ÐÒÏÕ ïðåäñòàâëÿåòñÿ ïåðñïåêòèâíûì íàïðàâëåíèåì â ñîâðåìåííîé òðàíñïëàíòîëîãèè, ïîñêîëüêó ïðîâåäåííàÿ èììóíîàáëÿöèÿ íå ïîçâîëÿåò ïîëó÷èòü àóòîÌÌÑÊ
èç êîñòíîãî ìîçãà ïàöèåíòà, ò.ê. îí ïîðàæåí îíêîëîãè÷åñêèì
ïðîöåññîì.
 ïîñëåäíåì íîìåðå æóðíàëà Pediatr. Transplantation
áûëî îïóáëèêîâàíî êëèíè÷åñêîå íàáëþäåíèå òðàíñïëàíòàöèè àóòîãåííûõ ÌÌÑÊ æèðîâîé òêàíè ïîäðîñòêàì ñ ÿâëåíèÿìè ÐÒÏÕ â âèäå òÿæåëîãî ýíòåðîêîëèòà. Ìàëü÷èêó 15 ëåò
áûëà âûïîëíåíà àëëîãåííàÿ òðàíñïëàíòàöèÿ ïóïîâèííîé
êðîâè â ñâÿçè ñ õðîíè÷åñêèì ìèåëîëåéêîçîì â ðåçóëüòàòå
íàñëåäñòâåííîé ïàòîëîãèè – òðàíñëîêàöèè t(9;22)(q34;q11)
(ôèëàäåëüôèéñêàÿ õðîìîñîìà). Ìàðêåðîì õðîíè÷åñêîãî
ìèåëîëåéêîçà ÿâëÿåòñÿ ðåöèïðîêíàÿ òðàíñëîêàöèÿ
t(9;22)(q34;q11), êîòîðóþ îáíàðóæèâàþò ó 90-95% áîëüíûõ.
 ðåçóëüòàòå ýòîé òðàíñëîêàöèè ìåæäó äëèííûìè ïëå÷àìè
9-é è 22-é õðîìîñîì ïðîèñõîäèò óêîðî÷åíèå äëèííîãî ïëå÷à 22-é õðîìîñîìû. Èìåííî îíà îòâåòñòâåííà çà ðàçâèòèå
õðîíè÷åñêîãî ìèåëîëåéêîçà.
Ïîñëå ðåíòãåíîòåðàïèè è õèìèîòåðàïåâòè÷åñêîé èììóíîàáëÿöèè áûëà âûïîëíåíà àëëîãåííàÿ òðàíñïëàíòàöèÿ ïóïîâèííîé êðîâè. Îäíàêî ñïóñòÿ íåêîòîðîå âðåìÿ ó ïàöèåíòà
ðàçâèëàñü ÐÒÏÕ. Ñòàíäàðòíàÿ òåðàïèÿ íå áûëà óñïåøíîé.
Äëÿ êîððåêöèè èììóííîãî êîíôëèêòà áûëà âûïîëíåíà àóòîòðàíñïëàíòàöèÿ ÌÌÑÊ æèðîâîé òêàíè ïàöèåíòà. Íà ôîíå ïîëó÷àåìîé ñòàíäàðòíîé òåðàïèè ÿâëåíèÿ ÐÒÏÕ ñíèçèëèñü è
ìèíèìèçèðîâàëèñü, ÷òî áûëî ïîäòâåðæäåíî áèîïñèåé ñëèçèñòîé îáîëî÷êè òîëñòîé êèøêè.
Âòîðîå íàáëþäåíèå èììóíîêîððåãèðóþùåãî ñâîéñòâà
ÌÌÑÊ æèðîâîé òêàíè áûëî ó äåâî÷êè 12 ëåò ïîñëå òðàíñïëàíòàöèè àëëîãåííûõ ãåìîïîýòè÷åñêèõ êëåòîê ïåðèôåðè÷åñêîé
êðîâè. Èììóíîàáëÿöèÿ îñóùåñòâëÿëàñü õèìèîòåðàïåâòè÷åñêèìè ïðåïàðàòàìè. Òàêæå, íåñìîòðÿ íà èììóíîñóïðåññèâíóþ òåðàïèþ, íå óäàëîñü èçáåæàòü ÐÒÏÕ ñ ïðåîáëàäàíèåì
ïîðàæåíèÿ òêàíè ïå÷åíè. Òðàíñïëàíòàöèÿ ÌÌÑÊ æèðîâîé
òêàíè ïîçâîëèëà ìèíèìèçèðîâàòü ðàçâèâøååñÿ îñëîæíåíèå
â òå÷åíèå áëèæàéøèõ òðåõ íåäåëü.
Òàêèì îáðàçîì, àâòîðû äåëàþò çàêëþ÷åíèå îá ýôôåêòèâíîñòè àóòîòðàíñïëàíòàöèè ÌÌÑÊ æèðîâîé òêàíè ó ïàöèåíòîâ
ñ ÐÒÏÕ è ïîñëåäóþùåì ñíèæåíèè äîç ãëþêîêîðòèêîèäîâ è
öèòîñòàòèêîâ, ÷òî áëàãîïðèÿòíî ñêàçûâàåòñÿ íà ïðèæèâëåíèè
àëëîòðàíñïëàíòàòîâ ãåìîïîýòè÷åñêèõ êëåòîê ó äåòåé â óñëîâèÿõ íåâîçìîæíîñòè ïîëó÷åíèÿ ÌÌÑÊ èç êîñòíîãî ìîçãà.
ËÈÒÅÐÀÒÓÐÀ:
1. Bacigalupo A., van Lint M., Frassoni F. et al. High dose bolus
methylprednisolone for the treatment of acute graft versus host disease. Blut.
1983; 46(3): 125-32.
2. Blaise D., Bay J., Faucher C. et al. Treatment of steroid-resistant acute
graft-versus-host disease with anti-thymocyte globulin. Bone Marrow
Transplant. 2001; 27: 1059–64.
3. Chen X., Armstrong M., Li G. Mesenchymal stem cells in
immunoregulation. Immunol. Cell Biol. 2006; 84(5): 413-21.
4. Haniffa M., Wang X., Holtick U. et al. Adult human fibroblasts are potent
immunoregulatory cells and functionally equivalent to mesenchymal stem cells.
J. Immunol. 2007; 179(3): 1595-604.
5. Lazarus H., Haynesworth S., Gerson S., Rosenthal N., Caplan A.. Ex vivo
expansion and subsequent infusion of human bone marrow-derived stromal
progenitor cells (mesenchymal progenitor cells): Implications for therapeutic use.
Bone Marrow Transplant. 1995; 16: 557–64.
Ïîäãîòîâèë À.Â. Âîëêîâ
Ïî ìàòåðèàëàì: Fang B., Song Y., Lin Q. et al. Human adipose tissue-derived mesenchymal stromal cells as salvage therapy for
treatment of severe refractory acute graft-vs.-host disease in two children. Pediatric Transplantation 2007; 11: 814-17
Êëåòî÷íàÿ òðàíñïëàíòîëîãèÿ è òêàíåâàÿ èíæåíåðèÿ Òîì II, ¹ 4, 2007