Дата: 2008-02-28 19:03
????????? ????????????????? (????????????? ?????).
?.?. ???????, ????????????? ?.?., ???????? ?.?.


Cellular cardiomyoplasty. The article reviews the current data about cellular cardiomyoplasty as a new therapeutic strategies of cardiac insufficiency. Animal experiments show the possibility to aug-ment the contractile function of diseased by intracardiac transplantation of different type donor cells: cardiomiocytes, skeletal myoblasts, smooth muscle cells, gene-modified cells and bone marrow cells. The possible mechanisms and path ways of improving of cardiac function after cellular cardiomyoplasty are discussed.

???????? ??????, ?????????? ??????????? ?????? ? ????????? ????????????????? - ????? ??????????????? ????????? ??????? ????????? ???????????????. ???????????? ?? ???????? ???????? ??????????? ?????????? ?????????????? ??????? ??????????? ???????? ??? ???????????????? ?????????????? ????????? ????? ????????? ??????: ??????????????, ????????? ??????????, ?????????????? ??????, ???-???????????????? ?????? ? ?????? ???????? ?????. ????????????? ????????? ????????? ????????? ??????? ?????? ????? ????????? ?????????????????.

????????
????????
? ??????? ? ?????????????? ???????????? ????????
????????? ?????????????????: ?????????? ?????? ? ?????????? ?????????? ??? ? ????????????? ?? ????????
???????? ????????? ?????????????????
??????????.
??????????
????????

????????? ??????????????? (??) ???????? ????? ?? ??????? ??????? ??????????????? ???? ???????????? ???????? ????? [1,19].

??? ??????? ?? ? ????????? ????? ?????????? ??????? ?????? ????????????? ?????????? ? ????????????????? ???????, ????? ??? ?????????? ????????????, ?????????????????, ????????????? ??????, ?????????????? ??????, ???????????????? ? ??. ????? ???, ??????? ???????? ? ?????????????????? ?? ? ???????????? ????????? ?????????, ?????? ??????? ?????????? ????????????? ? ?????????? ????????????? ?????, ????????? ? ??????????? ??????? ????????? ??.

???????? ?????????????, ???????????? ? ????????? ???????? ??????? ?????? ?? ?????? ??????? ???????? ???????????, ?? ? ????????? ??????? ?????? ???????????. ???, ??? ?????? ??? ??????? ????????? ??????? ??????? ???????????? ?????????????? (??) ??????? ??????????? ?????? ????????????? ??????, ??? ??????? ????????? ???? ?????????? ??????????????? ??????????? ?????????????????? ??????????? ????????? ????????????? ???????????, ??? ??????? ?????????? ????? ?????????? ?????? ???????????????????, ????????? ??????? ???????????? ??? ??????? ???????????? ??????? ? ?.?. [9,11].

????? ??? ??????????? ????????? ?????????? ? ??????????? ???????? ?????????????? ? ????????????????. ????? ?? ?????? ????? ???????? ?????????? ??????? ? ?????????????? ? ?????????????? ???????????? ????????.

????????
????????
? ??????? ? ?????????????? ???????????? ????????
????????? ?????????????????: ?????????? ?????? ? ?????????? ?????????? ??? ? ????????????? ?? ????????
???????? ????????? ?????????????????
??????????.
??????????
? ??????? ? ?????????????? ???????????? ????????

????????? ?????????????? ???????? ? ???????? (?) (??????? ????????, ?????????????? ????????????? ?????????????? ? ??.) ?????????????? ??? ??????????? ??????????????????????? ???????????? - "????????????????". ??????????????? ???????? (??) ???????????? ????? ??????? ???????????????? ????????????? ???????????????????????? ????????? ????? ?????? ? ?????????? ?? ???????????.

????? ?????? ??????? ????????????? ?? - ?????? ??????? ????????. ??? ???????? ???????? (??) ???????? ??????????????? ??????????? ??? ??????????????? ???????, ??? ? ???????? ?. ?????????? ???? ?????????? ????????????? ? ???????????? ??????????, ? ???????????? ??????? ???????????????? ? ????? ????????????, ???????????????? ? ????? ???????? ????????????????. ??????????????? ??????????? ????????? ? ????????? ??????????, ?????????? ?????????? ????? ???????????????, ???????????????. [1,5,19].

?????????? ?????????????? ??????????? ?????????????? (???) ???????? ????????????? ????? ????? ?????????????? ??????: ??? ?? ?????????????, ????????? ??????? ????????? ????? ?????????? ??? ?? ???????, ? ???????? ?? ???? ???????????? ?????? ?????? (????????????) [27]. ?????????, ??? ???? ???????? ??????????? ????????? ?????, ?? ??? ?????????? ? ??????????? ?? ?? ?????????????? ????????, ????? ??????????? ???????????? ????????? ?? ? ??????? ?????????? ??????? ??? ??? [13].

????? ???, ? ??????? ????? ?????????? ???? ??????? ??????????? ???????? ?????? ?.?. ????????? ? ?????. [7,8]. ??? ?????? ????????, ??? ? ????? ??????? ? ??? ???????? ?????????????? ? ??????????? ?????????? ?? ???????? ???? ?????????? ??????, ??????? ?????????????? ?????????????????? ??? ??????????????????????? ?????????. ???? ?????????????? ?????, ??? ??????? ???????????????? ???????? ????? ??? ???????? ????????? ??????? ????? ??????????? ????????, ??? ? ????????. ????????????? "??????????" ???????? ???????. ????? ?.?. ?????????? ???? ????????, ??? ? ????????, ?????????? ??????????????? ????????, ?????????????? ?????????? ?????????? ??? ????????? ??????????? ?, ??????????? ????????? ???? ? ?????? ????????????? [6].

?? ?????? ?.?. ????????? (1982) [12], ??? ?? ????? ???????????????, ??? ??? ?????? ??????????????? ???????? ?????????????? ?????? ? ??? ??????? ??????????? ??? ?????????? ??? ??????; ?????? ??????? ??? ?????????? ??? ?????????? ????????? ???????? ?????????? (????????? ?????????????????). ??-?? ?????????? ??????? ??? ?????????? ???? ?????????, ? ?????????, ??? ?? ???????????? ??????? ? ??? ?????? ?? ???? ?????? ???????????, ? ??????????? ????????????? ????????????? ???????????? ???. ????? ????, ? ????? ? ?? ??????? ?????????, ???????? ??????????? ??????? ????????? ????, ??????? ???????? ????????? ????????? ? ????? ??????? ????????? ? ????????????? ???????. ????? ???, ? ?????????? ???? ?????????????? ????????? ??? ? ?????????? ?? ????? 10%, ??????? ????? ???????? ? ???????????? ???? (??????????? 3?-???????). ?????? ???????? [25], ??? ?????? ???, ??????????????? ???????????, ?????, ????????????? ? ???????? ? ?????????????? ??????? ?, ?????????????, ?? ????? ????????? ?????? ? ?????????? ??. ?.?. ???????? (1979) ???????, ??? ?????????? ???????? ?????, ?????????? ? ?????? ?.?. ?????????, ??????? ?? ? ???????????? ????????????, ? ? ??????????????? ????????? ???? ??????? ?. ? ??????? ????????????? ?? ?????? ??????????????? ??????????? [13] ?????? ????????? ? ???????, ? ??????? ??? ??????????? ??????????? ?? ??????????????? ???????? ? ?????????, ? ????????????????? ??????? ??????, ??????? ????? ??????????. ? ???? ??????? ??????? ???????, ??? ??????? ??????? ??? ? ? ??????????? ?? ?? ???? ?? ????????????, ? ??????????? ??????????????? ????????????????? ???????.

? ????????????? ????????? ??? [55] ????????, ??? ??????????? ???????????? ????? ??????????? ???????? ?????? ????????? ???????????, ???? ????????????????? ? ?????????????? ????????? ?????. ??????, ????????? ?????????? ?????????????? ???????????? ? ???? ??????????? ??????? ????????????????? ????????? ?????????????? ?????.

????????? ????? ???????????? ??? ? ???????????? ???????? ? ??? ??????????????? Kajstura et al. (199 [25] ????? ????????? ????????????? ??????? ??? ? ?????????, ?????????? ?????????????? ??????, ? ? ??????? ? ????????????? ???????????????. ???????, ??????????? ????? ????????, ????????, ??? ???? ? 45-??????? ????????? ???????? ????????????? 5.8?109 ???? ??? ? ????? ????????? (??), ? ???????????? ?????? ??? ?????????? 14 ?? 106, ?? 81.2?103 ???? ??? ???????????? ????????? ? ????????? ??????. ???????????? ?????? ?????? ?????? 1 ????, ??????, ????? 0.71?109 ???? ??? ????????? ????? ? ?????????? ? ?? ??? ? ??. ??? ??? ??????????? 1-, 2- ? 4-??????? ??? ? ?? ?????????? 2/1/1 [2], ?? ????????????? ??????? ??? ????? ????????? 0.4?109 ? ???. ?? ?????? ??? ?? ??????? [25], ???????????? ?????? ??? ? ?????????????? ?????? (??????????????) ???????? ? 10 ??? ????, ??? ? ?????????? ????????, ?????????????, ???????????? ??? ?????? ?????? ???? ? ?????????????-????????????????? ????????? ??????????????? ?.

??????????? ??????? ?????? ??????? ??????????????, ????????? ? ?????????? ??????????? ???????? ? ????????????????? ????? ???. ???? ?????????? ??????? ?? ????? ?????????????? ????????? ?????? ??? ??? ?? (???????? ????? ??????? ???????? ??????), ??????? ????????, ??? ????????? ?????????? ????????? ??? ????? ???????????? ? ??????????????? ??????????? ??? ????? ????????? ???????????? ?????????????? ?????? ????????? ?????.

????????
????????
? ??????? ? ?????????????? ???????????? ????????
????????? ?????????????????: ?????????? ?????? ? ?????????? ?????????? ??? ? ????????????? ?? ????????
???????? ????????? ?????????????????
??????????.
??????????
????????? ?????????????????: ?????????? ?????? ? ?????????? ?????????? ??? ? ????????????? ?? ????????

????????? ?????????????? ???????? ????? ?????? ??????????? ?? ????????? ? ?????????? ?????? ?????? (??????) [11]:

?????????????? ????????? ??????? ????????? ?????????????? ???????? ?????????? ?? ??????? ??????????????? ????????? ??????, ??????? ? ?????? ??????? ??????????? ? ??????? ????????? ??????????. ??????????? ????????? ?????? ????? ????? ????????????????? ????????? ??????? ????????? ??????????????????, ??? ?? ??????? ????????? ??????? ?????????????????????? ?????????? [14];
????????? ????????? ???????? ? ????????? ?????? ????? ??????? ????????? ????? ? ????????????, ?????????? ??????????? ? ??????????????? ? ????????????? ????? ??????? (????????? ?????? ??????????? ??????? ????? ? ???????????);
???????? ?????? ????? ???????????? ?? ????? ? ??????????? ?????????;
????????????? ? ????????? ?????? ? ????? ????? ????????? ???????? ?????? ? ????????? ???????????;
????????? ????????? ?????????????? ??????????? ????, ??? ????????? ??????. ????????? ?????? ? ? ????? ??????????? ??? ????????? ?????????????? ???????? ????????????? ??? ???????? ?????? ????? ??, ??? ????????? ?????????????? ??????? ??????, ????????? ????????? ??????????????? ?? ????? ?? (?????????? ??????? ??????????, ?????????????? ?????????, ????????? ??????????????? ??????????, ?????????????? ?????????? ??????? ???????), ??? ??????? ????????????? ?????????????? ? ?????? ?????.

??? ???? ????????, ??? ?????????????? ??????? ? ????? ???? ?????????? ????? ?????????? ?????????? ?????????????? ????????? ????????? ? ? ?/??? ????? ????????? ??????????????? ??????? ??? ?????????? ?? ???? ?????????? ? ??? ????????? ??????????????? ???????????. ??? ???? ????? ?????????? ????????? ? ??????? ???, ?????????????? ??????, ???-???????????????? ?????? (???????????, ????????? ?????????), ???????? ???????????????? ?????????? ???????????? ????? ?????????? ????? ??? (????????????? ????????????) ? ?????????? ?????? ??????????????????? ?????? ????????? ??????? [11,31,40]. ??? ??? ????????? ???????? ???????? ??????????????? ???????? ???????? ??, ???????? ?? ??? ??????????? ? ? ???????? ????? ???????? ??????? ????????? ?????, ?? ??? ????????? ?????????? ? ??????????? ????? ?????????? ???????? "????????? ?????????????????".

????????? ?????? ???????????? ????? ????????????? ????? ??????????? ????????????????? ???????????? ?? ?? ? ? ?????? ????????? ?????????. ?????? ? ???? ??????? ????????? ??? ???????? ???????: 1) ???????????? ?? ???????????? ?????? ? ??? ??? ???????? ????????? ?; 2) ?????????? ?? ??????? ????????? ????? ????? ??????????????.

??????????????? ????????? ???????????? ?????? ? ???????? ??????????? ????? ?????????????? ??????

????????? ???.

????????, ??? ??? ?????????????????? ????????????? ??????????????????? ?????????? ? ??????? ?????????? ??????, ? ??????? ??????? ??????? fascia adherens (???? ???????????? ??????????), ??????? ????????, ?????????. ????????? ? fascia adherens ????????? ???????????? ???????, ???????? ??? ????? ?????, ? ??????? ????????? ????????? ???? ?????????? ????????????? ?????????. ??????????????????? ?????????? ????? ??? - ?????? ????????????????? ?????????? ?, ?? ???? ??????? ????????? ????? ????????? ??? ?????? ?????. ???? ?? ?????????? ????????, ???????????? ? ? ????? ????????? ? ???? ????????? ????? ??????, ? ??????? ?????????????? ??????????????????? ?????????? ??? ?????? ? ??????????.

???, Klug et al (1995) [30] ????? 10 ?????? ????? ????????? ????????? ??? ????????? ????????? ???? ??????????? ?????????? ?????? ????? ??? ??????? ? ?????????? ??? ? ? ?????, ?????????? ?????????????? ???????? ??????????.

Leor et al (1996) [34], ?????????????? ?????????? ????????? ????? ?????? ?????? ?? ????????? ?????? ????? ??, ?????, ??? ?????? ?????????? ?? 65 ????, ????????? ????????? ??????? ? ?? ?????????????????? ? ?????? ???. ? ??????? 1996-97 ??. [37,38,39], ??????????? ????????? ????????? ??? ? ??? ????????????? ????, ???? ??????????, ??? ???????? ??? in vitro ?????, ???????? ???????????????? ????? ? ?? ????????, ? ?? ???????. ??? ????????? ?????????????? ????????? ? ???? ????????? ????????????? ??????????, ??????????? ????????? ? f. adherens. ??? ?????????, ????????? ? ????????? ??????????? in vitro. ????????? ???? ?????? ???? ?????????? ? ???????????????? ? ? ??? ???? ????? ????. ????? ????????? ??? ????????? ? ??????? 8 [37] ? 24 [39] ?????? ??? ????????? ? ? ? ? ??????? 3-? ??????? ??? ?? ??? ???? [38]. ???? ????????, ??? ???????????? ??? ????????? ???????????????? ?????: ?????????? ?????????? ????? ??????, ??????????????? ?????????????? ????? ? ??????????, ????? ????????????????? ???????? ??????????? ????????? ? f. adherens, ?????????? ??????????, ??????????? ??????? ????????? ??????????????? ?????. ???????? ?? ?????????? ????????????, ? ?????????? ????? ????? ?? (24 ??????) ?????? ???????????? ?????? ????????? ???????? ???????????? ?????????? (????????????? ????????????, ?????????? ???????? ?????????????) [39]. ????????????? ?????? ???????, ??? ?? ???? ????? ???????? ??? ???????? ????????? ??? (???????? 92% ??????), ??? 5-??????? (?????????????) ??? (50%), ? ??????, ?????????? ?? 22-??????? (???????) ? 32-??????? (????????) ???????? ?????? ?? ???????? ? ?????? ????? ?? [38]. ????????? ???? ??? ??????????? Reinecke et al. [51], ??????? ??????????, ??? ???????? ??? ?? ???????? ??? ?????????.

??????, ????? ??????? ???????????? [53] ????????, ??? ?? ?????????? ???????? ??????????? ??? ? ???????????????? ? ????? ???? ? ??????????? ?? ? ???????? ????? ? ??????? 5 ?????? (???? ????????????). ???????????? ?????? ?????????????? ??????? ??????????????? ??: ?????????????? ?????????????? ??? ????????? ? ????????? ?????, ?????????? ??????? ??? ??????. ????? ???????? ???? ??????????? ??????? ???????????? ????????? ???, ?????????? ? ??????? ??????????? ???????????? ????, ?? ??????????? ????????????????? ? ? ??? ???? ????? ???? [36]. ????? ???????????? ????????? ??? ???? ???????? ???????? ?????????? ?????????? ??????????????? ? ??????????? ?????????????? ????????????? ??? ????????? ???????????????? ??????? ?, ???? ???????? ?????? ?? ?????????? ?? ??????????? ???????? ? ???????????? ???????. ????? 5 ?????? ????? ?? ???? ?????????????????? ??????????? ???????????? ?????? ? ?????????? ? ?????????????, ? ????? ???????? ?????????? ??????????? ???????. ???????? ?? ??, ??? ? ????????? ????????? ?? ???? ?????????????? ??????, ????????????? ???????? ???????????? ?????????? ? ?????????????. ????????? ?????????? ???????????, ?????? ???????? ???????, ????? ?? ??????????????????? ??? ??????????? ? ??????? ?. ??? ????????? ????????? ??????????? ? ?????????? ??? ? ????? ? ???? ????? 7 ???? ????? ?? [33] ????? 3 ?????? ???? ???????????, ??? ??? ? ?????????? ?????????? ?????????? ??????????? ?????????????? ????? ? ??????????? ??????????? ????? ???????.

????????????????? ?????? Matsushita et al (1999) ???????? ? ?????? [43], ??? ?? ?????? ??????? ?? (48 ?????), ??????????? ??? ? ?????????????? ???????? ????????? ???????????? ??????, ???????? ???????? ?????????; ??????? ???????? ??? ???? ????????. ? ???????? ??? ? ??????? ?????????? ??????? ? ?????????? ?????????, ????????, b1-?????????. ????? 3-? ????, ??????? ???????? ? f. adherens (??????? ???????????? ???????) ??????? ????????????? ??????? ??? ????????? ??????? ????????? ????? ????????? ???. ? ?????????? ????? (60-90 ???) ?????????? ?????????? ?????????? ?????????, ??? ??? ?? ????????? ????? ?????, ? ? ????? ?????? ??????????. ????? ???????, ???????? ?????????????????? ??????????? ???????????? ??? ???????? ??????????????, ????????, ??? ??? ?????????????? ??????? ????????? ??????????? ? ??????????? ????? ???????????? ?????????. ?? ?? ?????? ??????? ????????????? ????????? ????????? ????? ????????????? ??? ? ???????? ?????????? ? ???? ??????? ?????????????????? ?? [44]. ??? ???? ???? ????????, ??? ??? ????????????? ??????, ???????????? ? ?????????????? ????? ?, ????? 4 ??? ???????????? ?????????? ? ?????????? ??????? ???????? ???? ? ?????? ? ? ??? ???????. ?????? Reinecke et al (1999) [51] ?????? ???????????????, ??? ????? 2-8 ?????? ????? ????????? ??? ? ????? ??????????? ??????????????????? ?????? ???? ???????? ?? ? ?????????? ?????????????? ??? ???????? ??????. ????????? ???????? ???????????? ?????? ? ? ??????? ????? ????? ?????? ? 40% ??????. ????? ???????, ????????? ??? ? ???????? ????? ? ??????? ?????, ????? ???????? ??????????????? ??????????? ??????????? (????? ????? 1 ???.), ???????? ? ???????? ???????????? ?????? ?? ?????????? ?; ?????? ?? ??????????? ???????????????????? ???????? ????? ?????????????????? ??? ? ??? ?????????? ????? ???????? ???? ??? ?? ???? ????????.

??? ?????? ????????? ????????????, ??? ????? ????????? ??? ? ? ???????????? ???????????? ?????????????? ?? ? ????????? ???????? ?????????? ? ???????????????. ? ???? ???????? ??????????? ??????????? ??????????? ????????? ????????? ????? ??? ?????? ? ??????????. ??? ????????? ?? ??? ? ????? ???????? ??????????????????? ?????? ? ???????? ????? ?? ????????? ????????? ?? ??????????? ??????? ???????????? ?????? ? ??????? ? ??????????. ??????? ? ?????????? ??? ? ??????????? ???? ?? ????? ??????? ????? ????????????? ? ????????? ??????????? ????????? ????????? ????? ??? ?????? ? ??????????.

????????? ????????? ??????????

????????? ????????? ?? ???????? ????????? ??????????? ? ???? ??????????? ??????, ??? ?????????? ???????????? ????? ???????????? ?????????????????? ???????????, ?? ?????????? ??? ?????????? 4-8% [66]. ??????????? ??????, ??????? ?????????? ????????, ???????? ??????????????? ? ?????????????????? ? ?????? ????????? ???????, ???????????? ????????? ??????? ??????????? ????????? ???????????. ? ????? ? ????????????? ???????????? ????? ????????? ???? ???????????? ???????????. ? ??????? ?? ????????? ???????? ??????, ??????? ????????? ????? ???????????? ??????????? ???? ?? ?????.

?????? ?????? ?? ????????? ????????? ?????????? ? ? ????????? ? 1993, ????? ? ???????? ????????????? ???? ???????????? ??????????? ????????? ????? ????????? ??????? ??????????, ?????? ??????? ???? ?????????? ? ???????? ? ????? [29]. ??????????? ?????? ??????????? ? ??????? 3-? ???????. ???????????????????? ? ????? ????? ???? ???????? ??????? ?????????????????? ???????? ???????? (?????????? ????????? ???????? ??????? ???? ???????), ??????????? ??????????? ?? ???????? ??????? ????????? ????? ???????? ????????????? ? ???????. ???????? ?????????? ???????? ???????? ???????, ??? ?????????? ??? ???????????? ????????? ??????? ???? ??????? 2 ?????? ??????????? ?????????. ????? ???????, ? ??????????????????? ?????????? ????? 3 ?????? ???? ??????? ??????????????, ???????? ??? ?????????????????? ???????? ????????.

Chiu et al (1995) [20] ????????? ????????? ??????????? ?????? ? ???????????? ? ?????. ??? ????????? ?????????????, ??? ????????? ????????? ????? ?????????????????? ? ??????? ????????? ????? ? ????? ??????? ??????????????? ???????????? ?. ??????????? ?????? ???? ???????? ?? ????????? ?????, ??????????????, ???????? 3?-????????? ? ???????? ? ???????????????? ?. ????? 18 ?????? ??????? ????????? ????? ? ???????? ???????? ????? ??????????? ????????? ?????????? ??????. ???? ???????? ??????????? ?????????? ?????? ????? ????????????? ???????? ? ??????? ?????????? ????????????? ???? ? ???, ???????? ??????? ? ???????? ????????? ?????. ??? ?????????? ????????? ??????? ?????????, ??? ??????????? ?????? ???????????? ??????????????? ? ???????????????? ???????? ?????? ? ??????????????? ??????????????. ???????????? Yoon et al (1995) [69] ???????????? ??? ??????????????? ??????; ????? ????, ??? ???? ??????? ????????? ???????? ????? ??? ? ???????????.

Murry et al (1996) [46] ?????????? ? ???????????????? ? ????????? ?? ????????? ???? ????????????? ????. ?????? ??????? ????? ????? ??????? ??????????? ???????? ????????? ??????, ?????? ??? ? ??? ???????????? ???????? ?????. ???? ???????????, ??? ????? 3 ??????:

???????????? ????????? ????????????? ? ?? 3 ???? ???????? ??????????? ???????????? ???????? ????????, ??????? ???????????????? ? ??????? ?????? ??????? ???????? ???????;
? ???????????????? ????? ? ?????????? ????????? ???????? ????????? ???????? ???????;
???????????????? ????? ????? ??????????? ??????????? ????????? ??????;
ex vivo ????? ??????????? ???????? ?????????? ????? ???????????? ???????.

? ??????? ?? ????????????? ????? [20,69], ? ???????????? Murry et al (1996) [46] ???? ? ?????? ???????? ?????? ?? ????????, ??????????? ??????????? ?? ??????????? ??????? ?????????? ??????, ????? ???? ??????????? ?? ? ???????? ??????. ???????????? ?????? ??????????????? ?????, ????????????? ??? ????????? ???? ? ?? ???????????? ????????????????????? ???????? ??????? a????? ???????. ?? ???? ?????? ?? ??????? ????????? ??????????????? ???????? ????????????? ???? ? ??????? ???. Taylor et al (199 [63] ????????, ??? ???????????? ???????????? ???????? ????????? ???????????????? ? ??????????? ???????, ?????????? ???????? ??????, ??????? ????????????? ?????? ?????????????? ?? ? ????????? ??????. ? ?? ?? ????? ??? ?????? ????????, ??? ??????? ??????????? ???? ? ?????? ???????????, ????????????? ?????????? ?????.

?? ????????? ?????? Reinecke et al (2000) [50], ???????????? ????????? ?????????, ???????????? ? ?, ????????????? ???????????? ?????????? N-cadherin ? connexin43 (????????? ?????????? f. adherens ? ??????? ????????? ??????????????), ?? ??? ??????????????? ??? ?????? ??? ????????. ? ??????? ?? ?????? Chui et al., Yoon et al. [20,69], ??? ?????? ?? ?????????? ? ????????????? ?????? ? ????????? ?????????: ????????????? ????????? ????? ??????????? ???????????? ??????? ??? ?????????? ??????, ??????????????? ???????? ???????, ????????????? ??? ????????? ?????, ?? ??????????????? ????????? a?????? ? ?????? ????????? ???????????? ?????????, ????? ?????????????? ????????, ????????????? ??? ????????? ????. ??????, ??? ??????? ???? ???????????? ???????????? ????????? ????? ?????????? ????????? ? ??? in vitro. ?????? ????????????, ??? ??? ???????? ?? ????? ????????????? ????? ????????? ??-?? ?????????????? ???????? ?????????? N-cadherin ? connexin43 ?? ??????????? ??????????????????? ????????? ????????.

????? ???????, ??????????? ???????????? ?? ????????? ???? ?????????? ???????? ?? ??????: ???????????????? ?? ????????? ? ???????? ?????????? ? ??? ? ?????????? ?? ??? ???? ???????? ????? ??? ?????????? ? ??????????? ??????.

????????? ?????? ???????? ????? ? ??????????? ????????????? ????????? ?????? ??????? ??????? ???? (???) ???????? ?????????????, ? ???????? ? ??? ?????, ???????? ????????? ??????. ????? ??? ???????? ??????????????? ????????? ??????, ????????? ??????????????? ? ?????????????????? ? ???????? ?????, ? ?????????????? ????????? ?????? (???), ??????? ????? ????????? ? ?????????????? ?????: ????, ????, ?????, ??????, ?????????, ??????? ????? [48,49].

????????, ??? ????????? ?????????????? ?????? ???????? ???????????? ? ?????????? ??????????????. ???, ? 1995 ???? Salvatori et al (1995) [55] ????????, ??? ??????????? ????? 10T1/2, ?????????????? ? ??????????? ????? C2C12 ??? ?????????? ??????????? ??????, ???????????????? ? ???????? ???????? (1-10% ?? ???? ?????????). ????? ?? ???????????, ????? ??? ?????????????????? ? ??????? ???????? (????????, ? ???????? ??????????????). ????????? ?????????????? ???????????? ????? 10T1/2 ??????????? ? in vivo ????? ???????? ?? ? ?????????????? ?????. ???????????? Ferrari et al (199 ????????????, ??? ?????????????? ?????? ?????, ????????? ? ????????? ?????, ????? ??????????? ? ???????? ?? ??????????? ? ??????????? ????????? ?????????????????? ???????? ??????? [22].

Makino et al (1999) [42] ???????? ??????????????? ????????? ????? ?? ??????? ?????? ?????? ???????? ?????, ? ??????? ????? ????????? 5-???????????? in vitro ???? ???????????? ???????? ??????????????? ? ???. ????????????? ????????? ????????? ~30%. ?????????? ?????? ??????????????? ????????? ????????????? ??? ??? ?????, ????? ??????? ????????? ???????????? ???. ?????????????????? ????? ??????? ??? ???? ??????? ????? ????? ??????????? ???????, ??????????? ???????? ????????, ????????? ???????????, ????? ???-???????? ???????????????, ??????? ???????? ?????????, ?????????? ????????????? ????, ????????????? ??????? ????????? ? ???????????. ???????? ???????? ???????????? ?????????? ????????, ???????????? ??????? ? ???????????? ???.

??????????????????? ? ??????? 7 ???? ? ?????, ?????????? 5-??????????, ???????????? ?????? ??? ???? ?????????? ? ???????? ????? ????? ?????????????????? ??, ?????????? ???????????????? ? ???? [65,66]. ????? ?? ? ????????? ??????? ??? in vivo ???????????????? ????????-????????????? ???????? I. ?????????? ?????????? ? ??????? ??????? ????? ????????? ??????????? ?? ????????? ? ?????????. ?? ?????????? ????????? ????? ? ???????????? ?????????. ?????????? ? ????????????? ?????????? ????????? ???????????? ???????.

Wang ? ?????. (2000) [67] ????????? ????????, ??? ?????????????? ? ? ??????? ???????????? ??????? ? ??????? ??? ??????????????? ??????????????? ???. ? ?? ????????????? ???????? ??? ????? ??????????????? ? ???????? ??????????? ??????????????? ????????? ?????? ???? ?????????? ? ? ? ?????????????????? ? ???, ???????????? ??????? ????????.

??? ?????, ? ??????? ?? ??????????, ???, ?????????? ????? ?????????? ?????????????????, ???????????? ????? ???????????? ??????????????? ???????????????.

????????????? ????????? ?????? (???) ????? ????? ??????? ?????????? ????????? ???, ?????????? ??? ????????? ? ?????? [28,67]. ??? - ????????????? ??????, ????????? ??????????? ? ????? ??? ?????. ??? ?????????? ?? ?????? ??????? ???????????? (??????????? ??????). ? ?????? Klug et al. (1996) [28] ????????????? ??? ???? ??????????? ?????????????? ??? ????, ????? ? ????????? ????? ?????????? ??????????????? ???? ?? ???????????????. ???? ???????????? ????? ???, ??????? ??? ????????? ??????? ???? ???????. ????????????????????? ? ????????????????? ???????????? ????????, ??? ?????????? ????? ???????? ??? ???? ?????? ???????????????? (99% ?????? ????????? ??????, ???????????, ?????????? ?????) ? ??????????? ????????????? ? ??????? ???????? ?????, ???????????? ? ??????? 7 ?????? ????? ?? ???????????.

????????? ?????????????? ??????

Li et al (1999) [35] ???????????? ? ?????? ? ???? ??????? ???????? ???????? ?????????????? ??????, ?????????? ?? ??????? ????????? ????. ?? ?? ??????, ????? 4 ?????? ??? ?????? ?????????????? ? ?; ??? ?????????????? ????? ??????????? ??????? ? ???? ?????, ?????????? ???????? ?????, ? ????? ??????????? ????????? ??.

Yoo et al (2000) [68] ???????????? ???????????? ?????????????? ?????? ? ?????? ??????? ? ?????????????? ????????????? ???????????????. ?????? ?? ?????????? ????? ?????????? ???????????? ????????? ?????? ? ?, ??????, ??? ???? ??????????, ??? ????? ???????????? ???????? ?????????????? ?????? ???????????????? ?? 25-35% ??????? ?? ? ???????????? ????????? ????? ??????.

????? ???????, ???? ????????? ????????, ??? ?????????????? ??????, ?????? ??????????????????? ? ??? ?????????? ??????????????? ??????????, ?? ????? ?????????????? ? ???????? ?????? ???, ?? ????? ??????? ???????????? ??.

????????? ???-???????????????? ??????

Soonpaa et al. (1994) [59] ???? ?????? ?? ??????, ??? ??????? ? ??????????? ?? ? ? ????????? ??? ?? ??????????? ????????. ??? ???? ???????????? ????????? ???, ?????? ? ??????????? ?????, ??????? ?????????????? ??? ??????? ???? ?????????? ??????? ? ????????? ???, ?????????? b-????????????? (?????). ? ? ???? ???? ???????? ??????????? ??????????????????? ?????? ? ??????? 2-? ??????? ????? ????????? ? ??????????? ?????????? ??????, ??????????? ???????? ????????? ??? ? ??? ???????. ???????????? ??? ???? ?????? ????????????????: ??????????? ??????????? ?????????, ??????? ?????????????? ???????????? ???????? ? ???????????, ???? ???????? ??????????, b-?????????????-?????????? ??????. ????????? ???????????? - ?????????????? ???????? ??? ????????, ?? ??? ??? ?????????? ??????? ?????????????? ?????????? ??????????????? ???????????? ??????. ??????????????? ????????? ????? ???????????? ??????????? ????????? ?????, ????? ?? ??????? ???????? MyoD. Tam et al (1995) [62] ????????????? ????????? ??????????? ????????????? ???? ????? MyoD ? ??????? ?????????????? ??????? ? ????????? ?????????????? ???????????? ? ?????? ????????? ????? in vitro. ????? 10 ???? ????? ??????????? ?????????? ???????? MyoD ???? ?????????????????? ??? ? 95% ??????.

? ?????? [45] ????? ???? ????????, ??? ????????? ??????????? ????? ???? ??????????????? ????????????? ???????? ? MyoD. ? ?????????? ?????????? ??????????????? ?????? ??????????? ??? ???????? ?? ? ???? ?????????????? ????? ? ????? ?????????????????? ?? ??????????? ??????? ?????? ????????? ?????.

???????????? Toma et al (1999) [64] ???????????????, ??? ???????????? ???, ????????????????? ????? MyoD ? ??????? ??????????????? ???????????, ????? ????????? ? ????????? MyoD, ???????, ????????????????? ???????, ????????? I ? a-???????? (????????? ????? ??????????????? ? ????????????? ?????? ????? ???????????, ?????? ?????????? ????? - connexin43 -?????????? ?? ????). ???????????????? ?????? ???? ???????? ? ?????? ??????????? ?????????????. ??? ??????????? ?? ?????????????? ?????????? ????????? ???????? ????????????? ???????, ?? ?? ? ??????? ?????????. ??? ?????????? ??????????, ??? ??? ????? ???? ?????????? ???????????????? ? ??????? ?????????????????? ????? ????? ?????????????? ?????????? ???? MyoD. ?????????? ???? ????????? ???????? ??????? ???? ??????? ???????????????, ?? ?????? ???????, ? ???, ??? ??? ?????? ????? ???? ???????? ????????? ??????? ???.

??????????????? ?????? - ????????? ???????????? ?????? ???????? ?????, ???????? ??????????????? ??????? ?? ????? ?? ???????????. ??????? ?????? ? ?????-???? ????? ????????????????? ?????, ??????? ? ????? ??????? ?????? ? ?????????????????? ???, ?? ????? ????????? ?? ??????????? ???????. ?????? ????? ????????? ???????? ????????? ??????, ????????????????? ????????????? ?????????????, ?????????????? ?? ?????? ?????????, ???????????? ??????? ?.

?????????????? ????????? ?????? ????? ????????? ????????????????? ?? ?????? ??????????? ?????????????? ?????? ?????????? ?????????????? ?????????? ?????? ?????????? ?????????? ????? ????????? ? ? ????????? ????? ??????. ?????? ?? ? ????? ???????????? ??? ?????????? ?? ?????????????????? ??? ????????? ?????????????? ?????????? ???????????? ??????, ???? ???? ?? ??????????? ? ???????? [16,28,38] ?/??? ???????????? ???????? ? ? ?????????? [43,44,69].

???, ?? ?????? Taylor et al (199 [63], ????????? ??????????????? ?? ???????? ?????????????? ??????? ??????, ?? ????????? ?????????? ??????? ?????. ? ?????????? ????????????? ??????? ? ??? ?? ?????????? ????? ??. ??????????? ????????? ????????? Atkins et al (1999) [17], Huteheson et al (199 [24]: ????? 3 ?????? ????? ???????? ?????????? ????????? ?????????? ? ??????????????? ???? ? ???????? ???? ???????? ????????? ? ?????????????, ? ?????????????? ??????? ??. ??????? ????????????? ?????????? ????????? ?????????? ? ????????????, ??? ????????????? ??????????, ??? ?? ????? ????? ?????? ???????? ?????????????? ???????? ?. ????????????? ??????????, ?? ?? ??????, ????? ???????????????, ??? ??? ??? ?????? ?????????????? ????? ??????????? ????????? ?????????????? ??????? ????????, ???????????? ??????? ????????? ?. ??? ????????????? ???????????? ????????? ????????? ????, ??? ????????? ????????? ????? ???????? ????? ? ???????? ????? ????????? ??????? ? ?????????? ??????????????? ?????.

????????, ??? ???????????? ????????? ?? ????? ??????????????? ??????????? ? ?????????? ?????????????? ???????. ?????????? ??? ? ???? ?????????? ?????? [45]:

????????? ????? ?? ???????? ????????????; ????????? ????? ????? ????? ???????? ????????????????? ?????????? ???????? ? ???????? ???????????? ??????, ??????? ?? ???? ?????????? ????????????? ?????????? ?????? ??? ????? ??????????? ???????; ????????? ?? ???????? ??????? ????????? ? ???????? ? ??????? [20,29,46,63]. ???????????? ??????????? ?? ??????? ??????????? ??????????? ??? ??????? ????????? ???????? ????? ? ? ????????????, ? ? ????????????? ??????? ?:

???, ??????????? ? ???? ????????, ????????? ????? ?????????? ????? [43,44], ? ??? ????? ???????? ?? ????????????? ??????????? ??????????? ???????? ? ??????? ?????????? ??????; ???? ?????????? ?????????? ????? ????? ??????????? ? ??? ? ???????? [50] ? ????? ?? ?????????? ? ? [69]; ??????? ???????? ????????? ??? ????????????? ?????? ????????? ????? ? ???????? ?????????????????? ? ????????? ?????? ?????????? [50]; ??????? ???????? ??????? ???????????? ?????????? ????? ?????????????????? ? ?????????? ? ????????? ????????? ???????? ???????. ??????? ????????????? ?????? [46], ??? ???????????????? ????? ????? ????????? ??? ?????? ??????. ??? ?? ????????? ??? ? ???????????? ??????? [37] ???? ?????????? ????? ????????? ???????? ?????????? ???????? ? ??, ???????? ?????? ?????????????? ?????? ?? ????????? ? ???????????? ????????. ????????? ??? ????????????? ??????????? ??????? ???????? ? ????? ?????????? ??????? ?? ?????? ??? (?? ???? ?????????? ???????? ???????????????? ???????) [56]. ?? ???????? ???????????? ??? ????????? ????????, ??????????? ?? ? ????????????????? ?????? ?? ????????? ? ????????? [53].

???????? ?.?. (1999) [16] ????? ??????????, ??? ??? ?? ????????? ??? ? ? ???? ????? ????????? ?????????? ??????? ?????????? ??????????? ???????????? ???, ??? ???????? ???????????? ??????????? ???????????????? ??? ? ????????????? ?????? ????????? ?????????.

????????? ???????????? ?????? ???, ???????????? 5-????????????, ????????? ? ?????????? ???????? ?????????????? ???????? ? ????????? ???????????? ????????????? ? ???????????? ??????????? ????? [66]. ?? ???????????? ?????????????? ?????? ? ??????? ? ?????????????? ??????????????? [68] ????? ???????????? ?????????????? ?? ???????????? ? ???????? ???????????? ?. ????? ???????????? ?????????????? ?????? ? ???????? ??????????, ?? ?????? ???????, ????????????, ??-?? ????????????????? ?? ???????????? ? ? ????? ??. ????????????? ??????? ????????? ?????????????? ??????? ? ? ??????????? ??????? ?????? ??, ??????? ???????????? ???????????? ?????????, ? ????????? ????????????? ??????? - ? ????????? ???????????, ? ?????????? ????????, ????????, ?????????? ???????????? ???????? ??.

????????? ?????????????? ?????? ????? ???????? ??????? ??????, ??? ??? ? ?????????????, ? ?????????????? ???????? ? ?????? ?? ???? ???????, ??? ? ???????? [35].

????????? ???????????? ????? ????? ?????????????????? ?? ? ???? ? ????? ??????????? ????? 1 ????? [4,5,56], ?? ?????? ??????????? ?? ????????? ????? ?????? ?? ??????? ? ??????? ??????????? ?? ???? ????????????? ???????????? ????????? ??. ? ?? ?? ????? ??? ???????? ? ???, ??? ????????????? ????????? ??????? ?????????? ??? ????? ?????? ?? ??????????, ?? ??????????? ? ????????? ????? ????????? ????????????????????? ?????. ?????? ? ???? ?????? ????????????? ??????? ???????????????? ????????? ??????????? ?????? ?????? ??? ????????? ????????? ?????????, ? ????????, ???????? ????????? ????????????????? ????????? ??????? ?? ??????????? ????????? ??????? ?. ??????? ???????????? ?????????????? ?????????????? ?????? ?????? ???? ??????????????? ????????.

????????
????????
? ??????? ? ?????????????? ???????????? ????????
????????? ?????????????????: ?????????? ?????? ? ?????????? ?????????? ??? ? ????????????? ?? ????????
???????? ????????? ?????????????????
??????????.
??????????
???????? ????????? ?????????????????

? ????????? ??? ?????????? ?? ?? ????? ???????????? ?????? ?? ??????, ????? ?? ??? ?????? ????? ???????????? ??? ????? ???????????? ?????????????? ??????? ?. ???????????? ????? ??????? ????????? ?????? ??????? ????? [24,54]. ? ?????? [54] ?????? ?????????? ? ? ??? ???? ??????: ????????? ???, ??????????? ? ?????????????? ??????. ???????????? ??????????? ?????????????? ???????????? ?????? ???????? ?????, ?? ???? ????????? ???????? ?????????? ??????? ?? ??????? ??????????????? ??, ?? ??????? ?????? ???????? ?????????????. ????? ????, ???? ?????? [24], ??? ????????? ????????????????? ?????????? ????? ????? ???????????? ????????? ?????????????? ?????????? ??. ????? ???????????? ??????? ?????????????? ??????????? ??? ??????? ????? ????????? ??? ? ?????????????? ??????, ??????, ????? ????????? ??? ????????? ??????? ? ???? ????? ????????????, ??? ??? ?? ?????????????? ??????. ?????????? ???????? ?????? ????????? ????????????? ???????????? ????????? ?????????? ? ???????????? ???????????? ???, ????? ??? ?????????????? ?????? ????? ???? ???????? ??? ??????????? ?.

? ????????????? ?? ????????? ?????????? ????????? ? ? ??????? ???????????? ???????? ??????? ??????????? ??????????? ? ????????? ????? ????? ??, ? ??? ?????????? ????????? ????????? ????????? ????????.

????????, ??? ???????????? ? ? ?????? ???????? ????????? ??????????? ????????: ???????? ???????, ???????? ? ??. ???????? ??? ???????? ????????? (? ??? ????? ? ?????????) ??????, ???????? ??????? ?? ??????????? ??????? ?????????? ? ?????? ???????? ???????????? ????????? ? ????? ??????????? [10,11,14,34]. ? ?? ?? ?????, ??????????????, ? ??????? ???????? ????????? ??????, ????? ????????? ??????? ?? ?? ????????. ???, ??? ??? ???????? ?????????????? ??????????? ? ??????? ??? [20,67], ?????? ????????? ? ??????? ????? ????????????? ???? ?? ????????????. ????????????? ??????? ? ???????? ????? ?????????????????? ? ??????? ??????? ???????? ? ????? ?? ??????????? ??????: ????????? (???????, ????????????? ??????????????? ????????) ????????????? ?????? ??????????? ?????????? ????? ?????????? ??? ? ????????????? ????? [23]. ????? ????, ????????????? ???????? ?????? ??????????? ???????? (????? ?????, ????????????????? ???????, ???????? ??????? ? ??.), ???????, ??? ???? ???????? [32], ? ???????? ???????? ??? ??????????? ?????? ?????, ?????????? ????????????????.

???????????? ?????? (????????? ??? ? ?????????????? ????????) ??????????? ?????????? [34,35], ??????? ??????????? ? ????? ? ?????? ????????????? [36-39,65,66]. ????? ???, ????? ???????? ???????????????? ??????????? ??????? ???? ???????? ????? ??????? [63].

???????????? ??????? ?????? ?? ??????????????? ? ???????? ??????????? ??? ?????????????, ?????????? ???????????? ?? ?????? ??. ?? ?? ??????, ?????????? ???????????? ???????? ?????: ?? ?????????? ????? ????????, ??????? ??????????????? ?? ? ????????, ?????? ?????? ??????????? ???????; ????????? ????????????? ?????????? (??? ????????????? ????????? ???????? ?????) [25,37-39,53,65,66] ? ??????? ????? [35]. ????????? ?? ?????????????? ????? ???????????? ????????? ??. ?? ? ????? ???????????? ?? ???? ????????, ??? ???????????? ?????? ???????? ????? ???????? ?????.

???????????? ?????? ? ??????????? ????? ??????????? ?????????? ?????? ???????????????? ?????, ??????? ??????????????? ? ? ??????? ? ????????? ???????. ? ????? ??????? ????????? ????????, ?????????? ???????? ?????? [63], ? ?????? ???????? ????????? ??????? ????????? ????????? ?????? ? ? ?????????? [50,67], ?? ???????? ??????? ? ??????? ?????????? ?? ??????????????? ????????? ????????? ?????? ?????????? ?? ????????; ???????? ???? ??????????? ????????? ????????????? ???????????. ??? ????????? ??????? ???????????? ?????? ? ??????? ?? ?????? ??????????? ????????? ???????:
?????? ?????? ????????? ?????????????? ?????????;
????? ???????? ?????? ?????????????? ?????????? ????? ? ???????? ?????????? ??? ?????????? ??????????? ??????????? ? ???????????? ??????? ?? ??? ???????; ?????? ????????????? ??????? ??????????;
???????????? ?????? ?????? ?????????????? ????????? ????????????? ??????? (????????? ?????????????? ????? ? ???????????? ??????????? ???????? ?????????????).

??????? ?????????? ????????? ????????? ????? ???????? ??????? ????????? ?????? ? [2,3]. ????? ???, ?? ?????? Murry et al. (1996) [46], ???????? ??????? ???????????? ?????? ????? ????????? ??????????? ?????????????? ??????????????? ????? ???????? (??????????) ??? ??????, ???????? ?? ?? ??????????, ????? ????????? ??????????? ? ???????????? ??????? ? ???????? ??????????. ????????, ??? ????? ??? ?????????? ????????? ??? ???????????? ???????????? ????????????????, ??? ???????? ??????? ?????? ??? ????????????? ?????????????? ???????????? ??????. ??????, ? ???????????? [44] ???? ??????????, ??? ??????????? ???????????? ??? ???? ??????????? ???????????? ??? ??????????.

????? ?????? ???????????, ?????????? ??????????????, ??? ???????????? ?? ?????, ?????? ????????????, ?????? ?? ??????, ??? ??? ? ????? ???????? ??????????? ??????????? ??????? ??????????????, ??????? ??????????? ?????. ???, ????? ????????? ????????? ????????????? ??? ? ???????????????? ???????? ? ????? 18 ????? ???????? ?? 45% ????????????????? ??????. ??? ?????????? ?????? ? ???????? ???????? ???????? ????????, ???? ????????? 3-10 ???. ??????, ? ??? ????????? 10-25 ???. ??? ?? ?????????? ????? ?? ????????????? [70]. ?????? ????? ??????? ????? ? ???????? ???? ????????????? ?????????. ??? ??????? ???????? ??????????????? ??????????? ?????? ????????????? [61] ?????????? ???????? ?????????? ???????????? "??????????" ????? ??: ????? ??????????? ??????? ?????????? ? ????????. ?????? ????????????? ? ??????, ??? ?????? ????????? ????? ???????????????.

?? ???? ???????? ?????? ????????? ??????????????? ???????? ??????????????????? ??????, ?????? ???????? ? ???, ??? ? ?????????? ????????? ????? ???????: 1) ?????????????? ???????? ?????????????? ?????????; 2) ????????? ????????? ??????????????? ??; 3) ?????????????? ??????????????? ????? ???????; 4) ????????? ?????????????? ??????? ?; 5) ????????? ?????????????? ??????? ??????.

????????
????????
? ??????? ? ?????????????? ???????????? ????????
????????? ?????????????????: ?????????? ?????? ? ?????????? ?????????? ??? ? ????????????? ?? ????????
???????? ????????? ?????????????????
??????????.
??????????
??????????.

? ????????? ????? ??????????? ????????? ????????????????? ????? ?? ?????? ????????? ????????? ? ? ?????????? ?????????. ???????? ??? ????? ????? ?????????? ??????????? ? ????? in vitro ? in vivo. ? ?? ?? ????? ????????? ?????? (? ?????????, ????????? ???) ????? ??????? ????????? ? ????? ??? ? ????????, ??? ? ? ????????? ?????????? ?? ????????? ?? ????????? ???, ??????? ??? ???? ? ?????????? ????? ??????????? ????????, ????????? ??????????? ??? ? ??. ????? ???, ????????????? ?????????? ????????? ??? ? ??????????? ???????? ?????????? ?? ????????? ???????????? ? ??-?? ????????????? ???????????? ???????????????, ??????? ? ???? ?? ?? ??????????? ??????????? ??????????? ????????????? ?????????.

??? ???????????? ?????????? ???????????????? ???????????? ????????, ? ???????? ???????? ????? ???? ???????????? ????????? ????????? ? ??? ???????? ?????, ? ????? ??????????????????? ??????. ??????????? ?????????? ?????? ????? ??????????? ???????? ??????? ? ???????????? ???????, ????????, ? ???????????? ??? ???, ? ????? ??????????????? ??????????? ???????? ???????, ? ????????, ??????? ????? ???????? ??????? ??? ???????? ??????????.

????? ?????????? ????????? ???????????? ?????? ??. ??? ????? ???????????? ?????????????? ????????????? ??????? ?????? ?????????? ???????? ??????, ??????? ???????? ?????????? ?????????? ? ????????? ? ??????????. ?????? ???????? ????? ????? ??????????????????? ???????????? ???????????, ????????? ?????????, ??????? ????? ??????????????? ??????????? ??? ??? ???????? ????????; ? ????? ???, ? ??????? ????? ???????????? ??????????????? ? ???.

????????? ?????? ? ? ????? ???????????? ??? ??????????? ????? ???? ??, ????????? ???????????? ??????? ????????????????? ????? ??????, ????????? ?????????????? ?. ???????????? ??? ???? ????? ?????? ?????? ?????? ????? ????????? ???????? ???????????? ???????? ???????? ? ????????? ??????? ??????? ?. ???????????? ?????????????? ??????, ????????? ????????? ????????????? ???? ????????. ??? ??? ?? ????? ????? ??????????????? ????????? ???? ?????????????? ?????? ??????, ?????????????? ?? ????????? ?????????, ??????????? ???????, ??????????? ??????????, ?????????? ???????????? ? ? ??????????????? ??? ??????.

?????????? ?????? ? ?????????? ??????????????? ??????????? ??? ???????????? ????????? ????????? ????????????? ???????? ???????????? ????? ??????????? ??? ????????? ????????? ???????? ? ?, ????????, ??? ??????? ?????? ??? ??? ???????????? ??????????? ?????????????? ????????.

???? ???????? ?????? ???????????? ?????????? ????????? ?. ??? ???????? ????????? (??) ?????? ????????????? ??????? ??????????? ??????????????? ? ???? ??????????? ?/??? ? ??????????? ????. ??? ????????? ????????? ????????? ????????? ????? (??????????????) ????? ????????, ??????, ?? ????? ????? ??????????. ? ????? ??????? ???????????? ???????????????? ???? ????????, ??????????? ?????????? ?????? ? ? ????? ?????????? [60].

???? ????????? ?????? ?????????? ?? ?????????????. ??????????? ?????? ? "??????" ???? ???????, ????? ????????? ?? ?????????? ??????? ??????????, ?????????? ???????????, ?????????????? ????????? ???? ??????? ? ? ???? ?? ????????? ?????????????? ?????????? ????????? ??????. ????????? ?????? ? ?????? ????? ??????? ??????????? ???????????? ?.

????? ???????, ? ????????? ????? ????????? ???????????????? ??????????????? ???????????? ?????????????? ??? ???????????? ???????? ?? ?, ??????????, ? ????????? ??????? ?????? ??????????? ? ??????????? ???????? ??? ????????? ???????? ? ??????? ? ?? ?????????? ?????? (??, ??????? ??????, ????????????? ?????????????? ? ??.).

????????
????????
? ??????? ? ?????????????? ???????????? ????????
????????? ?????????????????: ?????????? ?????? ? ?????????? ?????????? ??? ? ????????????? ?? ????????
???????? ????????? ?????????????????
??????????.
??????????
??????????

???? ???, ???????? ???, ??????? ??. ????????????? ??????????? ?? ????????? ???????????????. ?., 1995, 90?.
???????? ??. ??????????? ? ????????: ?????????????? ?????? ??????. ????? 1995; 119:454-459.
?????? ??. ????????????????? ?????????? ????????? ????? ? ???????? ??????????? ? ????????? ??? ????????????????? ???????? ????????. ??????? ???? 1989, 16 ?.
???????? ??. ???????????? ??????? ???????? ? ??? ????????? ??? ???????????? ??????. ??????????? 2000; 40:78-92.
?????????? ??. ?????????????? ???????? ? ??????????????? ??????. ???????????: ?????, 1981.- 324 ?.
???????? ??. ????????? ???????? ??????????? ????? ??????. ??? ???? ???? 1995; 115:198-212.
???????? ??. ??????? ??????????? ??????????????? ??????? ? ??????. ????? ??? 2000; 70:597-603.
???????? ??, ???????? ??, ???????? ??, ???? ??. ?????????? ??????????? ????? ??????. ?.: ?????, 1965.- 396 ?.
???????? ???????????????? ? ????????????? ???????. ????????? ??????? ??????? ?????? ??? ????. ?. 1994. - 142 ?.
????? ??. ?????????????? ??????: ????? ?????????? ? ????????. ????? 1998; 126(?????????? 1):14-28.
????? ??, ????? ??. ??????????? ????????? ????????. ?., ????: ?????, 1998. - 200 ?.
???????? ??. ????????????? ? ????????? ???????????, ??????????????? ? ???????????. ?. ?????, 1982.-288 ?.
???????? ??. ??????????? ? ?? ??????????? ????????. ?., ????????, 1979.- 284 ?.
????? ??. ?????????????? ????????? ?????? ? ??????: ????????? ? ???????. ????????? ????????????????? ???????? ? ???????? 1998; 126(?????????? 1): 3-13.
????? ??, ????????? ??, ???????? ?? ? ??. ???????????????? ??????? ?????????????? ????????? ??????. ????????? ????????????????? ???????? ? ???????? 1998; 126(?????????? 1): 178-181.
???????? ??. ????????????????? ??????????? ??????????? ??????????? ????????????? ?????????????? ? ??????????? ??????? ?????????????? ????????. ?????????? ???????? 1999; 25(4):109-17.
Atkins BZ, Huteheson KA, Hueman MT et al. Reversing Post-MI Dysfunction: Improved Myocardial Performance after Autologous Skeletal Myoblast Transfer to Infarcted Rabbit Heart. Circulation 1999; 100(suppl I):I-838.
Auer J, Berent R, Schleicher K et al. Stellenwert der Gentherapie in der kardiovaskularen Medizin. Herz 2000; 25:635-642.
Cleland JFG, McGowan J. Heart Failure due to Ischaemic Heart Disease: Epidemiology, Pathophysiology and Progression. J Cardiovasc Pharmacol 1999; 33(suppl. 3):S17-S29.
Chiu RC, Zibaitis A, Kao RL. Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg, 1995; 60:12-18.
Cossu G, Mavili F. Myogenic stem cells for the therapy of primary myopathies: wishful thinking or therapeutic perspective?. J Clin Invest 2000; 105:1669-1674.
Ferrari G, Angelis GCD, Coletta M et al. Muscle Regeneration by Bone Marrow-Derived Myogenic Progenitors. Science 1998; 279:1528-1530.
Gourdie RG, Wei Y, Kim D et al. Endothelininduced conversion of embryonic heart muscle cells into impulseconducting Purkinje fibers. Proc Natl Acad Sci USA 1998; 95:6815-6818.
Hutcheson KA, Atkins BZ, Hopkins MB et al. Comparing Cell Types for Cellular Cardiomyoplasty: Analysis of Improved Diastolic Properties with Autologous Skeletal Myoblasts and Fibroblasts. Circulation 1999; 100(suppl I):I-118.
Kajstura J, Leri A, Finato N et al. Myocyte proliferation in endstage cardiac failure in humans. Proc Natl Acad Sci USA 1998; 95:8801-8805.
Kessler PD, Byrne BJ. Myoblast cell grafting into heart muscle: cellular biology and potential applications. Annu Rev Physiol 1999; 61:219-242.
Kim WH, Joo CU, Ku JH et ak. Cell cycle regulators during human atrial development. Korean J Intern Med 1998; 13(2):77-82.
Klug MG, Soonpaa MH, Koh GY et al. Genetically Selected Cardiomyocytes from Differentiating Embryonic Stem Cells Form Stable Intracardiac Grafts. J Clin Invest 1996; 98:216-224.
Koh GY, Klug MG, Soonpaa MH et al. Differentiation and long-term survival of C2C12 myoblast grafts in heart. J Clin Invest 1993; 92(3):1548-54.
Koh GY, Soonpaa MH, Klug MG et al. Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs. J Clin Invest 1995; 96(4):2034-42.
Koh GY, Soonpaa MH, Klug MG et al. Strategies for myocardial repair. J Interv Cardiol 1995; 8(4):387-93.
Kubin T, Ando H, Scholz D et al. Microvascular endothelial cells remodel cultured adult cardiomyocytes and increase their survival. Am J Physiol 1999; 276 (Heart Circ. Physiol. 45):H2179-H2187.
Leor J, Aboulafia-Etzion S, Dar A et al. Bioengineered Grafts to Repair the Infarcted Myocardium. A New Approach to Repair the Infarcted Myocardium?. Circulation 2000; 102:[suppl III] III-56-III-61.
Leor J, Patterson M, Qumones MJ et al. Transplantation of Fetal Myocardial Tissue Into the Infarcted Myocardium of Rat A Potential Method for Repair of Infarcted Myocardium?. Circulation 1996; 94[suppl II]:II-332-II-336.
Li RK, Jia ZQ, Weisel RD et al. Smooth Muscle Cell Transplantation into Myocardial Scar Tissue Improves Heart Function. J Mol Cell Cardiol 1999; 31:513-522.
Li RK, Jia ZQ, Weisel RD et al. Survival and Function of Bioengineered Cardiac Grafts. Circulation 1999; 100[suppl II]:II-63-II-69.
Li RK, Jia ZQ, Weisel RD et al. Cardiomyocyte transplantation improves heart function. Ann Thorac Surg 1996; 62(3):654-60.
Li RK, Mickle DAG, Weisel RD et al. In Vivo Survival and Function of Transplanted Rat Cardiomyocytes. Circ Res 1996; 78 (2):283-8.
Li RK, Mickle DAG, Weisel RD et al. Natural history of fetal rat cardiomyocytes transplanted into adult rat myocardial scar tissue. Circulation 1997; 96(suppl II):II-179-II-187.
Li RK, Yau TM, Sakai T et al. Cell therapy to repair broken hearts. Can J Cardiol 1998; 14(5):735-44.
Liechty KW, MacKenzie TC, Shaaban AF et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 2000;6(11): 1282-6.
Makino S, Fukuda K, Miyoshi S et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 1999; 103:697-705.
Matsushita T, Oyamada M, Fujimoto K et al. Remodeling of Cell-Cell and Cell-Extracellular Matrix Interactions at the Border Zone of Rat Myocardial Infarcts. Circ Res 1999; 85:1046-1055.
Matsushita T, Oyamada M, Kurata H et al. Formation of Cell Junctions Between Grafted and Host Cardiomyocytes at the Border Zone of Rat Myocardial Infarction. Circulation 1999; 100[suppl II]:II-262-II-268.
Murry CE, Kay MA, Bartosek T et al. Muscle Differentiation during Repair of Myocardial Necrosis in Rats via Gene Transfer with MyoD. J Clin Invest 1996; 98:2209-2217.
Murry CE, Wiseman RW, Schwartz SM et al. Skeletal Myoblast Transplantation for Repair of Myocardial Necrosis. J Clin Invest 1996; 98:2512-2523.
Patterson MJ, Kopyov O, Kloner AR. Basic Fibroblast Growth Factor and Differentiation of Fetal Cardiac Myocytes. A Potential Improvement for Fetal Cell Transplant Therapy. Circulation 1999; 100(suppl I):I-164.
Pittenger MF, Mackay AM, Beck SC et al. Multilineage potential of adult human mesenchimal stem cells. Science 1999; 284:143-147.
Prockop DJ. Marrow stromal cells as stem cells for non hematopoietic tissues. Science 1997;276:71-4.
Reinecke H, MacDonald GH, Hauschka SD et al. Electromechanical Coupling between Skeletal and Cardiac Muscle: Implications for Infarct Repair. J Cell Biol 2000; 149:731-740.
Reinecke H, Zhang M, Bartosek T et al. Survival, Integration and Differentiation of Cardiomyocyte Grafts A Study in Normal and Injured Rat Hearts. Circulation 1999; 100:193-202.
Reinlib L, Field L . Cell Transplantation as Future Therapy for Cardiovascular Disease. Circulation 2000; 101(1:e182-e187 .
Sakai T, Li RK, Weisel RD. Autologous Heart Cell Transplantation Improves Cardiac Function After Myocardial Injury. Ann Thorac Surg 1999; 68:2074 -81.
Sakai T, Li RK, Weisel RD et al. Fetal cell transplantation: a comparison of three cell types. J Thorac Cardiovasc Surg 1999; 118:715-25.
Salvatori G, Lattanzi L, Coletta M et al. Myogenic conversion of mammalian fibroblasts induced by differentiating muscle cells. J Cell Sci 1995; 108:2733-2739.
Scorsin M, Hagege A, Marotte F et al. Does Transplantation of Cardiomyocytes Improve Function of Infarcted Myocardium?. Circulation 1997; 96[suppl II]:II-188-II-193.
Scorsin M, Hagege A, Vilquin JT et al. Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function. J Thorac Cardiovasc Surg 2000; 119:1169-1175.
Soonpaa MH, Daud AI, Koh GY et al. Potential approaches for myocardial regeneration. Ann N Y Acad Sci 1995; 752:446-54.
Soonpaa MH, Koh GY, Klug MG et al. Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium. Science 1994; 264(5155):98-101.
Suzuki K, Brand NJ, Morrison KJ et al. Development of a Novel Method for Cell Transplantation via Coronary Artery. Circulation 1999; 100(suppl I):I-164.
Suzuki K, Smolenski RT, Jayakumar J et al. Heat Shock Treatment Enhances Graft Cell Survival in Cell Transplantation to the Heart. Circulation 2000; 102[suppl III]:III-216-III-221.
Tam SK, Gu W, Nadal-Ginard B. Molecular cardiomyoplasty: potential cardiac gene therapy for chronic heart failure. J Thorac Cardiovasc Surg 1995; 109:918-923.
Taylor DA, Atkins BZ, Hungspreugs P et al. Regenerating functional myocardium: Improved performance after skeletal myoblast transplantation. Nature Medicine 1998; 4:929-933.
Toma C, Byrne BJ, Golob J et al. Efficient Myogenic Conversion of Human Mesenchymal Stem Cells with Forced Expression of MyoD. Circulation 1999; 100(suppl I):I-164.
Tomita S, Li RK, Jia ZQ et al. Bone Marrow Cells Transplanted in a Cardiac Scar Induced Cardiomyogenesis and Angiogenesis and Improved Damaged Heart Function. Circulation 1999; 100(suppl I):I-91-I-92.
Tomita S, Li RK, Weisel RD et al. Autologous transplantation of bone marrow cell inproves damaged heart function. Circulation 1999; 100(suppl II):II-247-II-256.
Wang JS, Shum-Tim D, Galipeau J et al. Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages. J Thorac Cardiovasc Surg 2000; 120:999-1006.
Yoo KJ, Li RK, Weisel RD et al. Autologous Smooth Muscle Cell Transplantation Improved Heart Function in Dilated Cardiomyopathy. Ann Thorac Surg 2000; 70:859 -65.
Yoon PD, Kao RL, Magovern GJ. Myocardial regeneration: transplanting satellite cells into damaged myocardium. Tex Heart Inst J 1995; 22:119-25.
Zhang M, Murry CE. Death of Grafted Cardiomyoctyes Limits Formation of New Myocardium in Injured Hearts. Circulation 1999; 100(suppl I):I-837

Наверх страницы