Sử dụng 5 - Azacytidine để biệt hoá tế bào gốc trung mô théo hướng cơ tim

TCNCYH 69 (4) - 2010

SU DUNG 5 - AZACYTIDINE DE BIET HOA

TE BAO GOC TRUNG MO THEO HUOfNG CO TIM •/- • » :

Tran Thj Thanh HUdng, Tran Van Khanh, Nguyen Thi Ha, D6 Doan Loi, Ta Thanh Van

,..., . TrUdng Dai iigc Y hia Ndi

Te bao ca tim thudc loai biet hda cao do vay viee tu tai tao trong cac trudng hap benh li nhoi mau ca tim

gay hoai tif te bao la rat han che. Lieu phap sd dung te bao gdc da biet hda nhSm tai tao md tim tdn thuang

dang gay duac nhieu su chu y. Muc tieu: (1) Ap dung quy trinh sd dung 5 - azacytidine de biet hda te bao

gdc trung md tiiy xuang theo hudng tao thanh te bao ca tim, (2) Danh gia kit qua ciia qui trinh biet hda te

bao gdc trung md tuy xuang ngudi theo hudng te bao ca tim bang 5 - azacytidine. Doi taang va phaang

phap nghien ciiu: te bao gdc trung md tuy xuang nguai (MSC); biet hda MSC bang 5 - azacytidine lOpM/24

gid, thai gian thu hoach mau sau biet hda la 3 - 4 tuan; danh gia ket qua biet hda te bao dUa vao: sU bieu

hien cac gen va protein dac trUng, sU hinh thanh cac cau true vi the ciia MSC. Ket qua: (1) 5 - azacytidine

lam thay doi MSC tuy xuang ngUdi theo hudng hinh thanh te bao ca tim sau 3 tuan biet hda,(2) Su biet hda

IvtSC theo hudng te bao ca tim dugc danh gia thanh cdng d 3 mUc: cac te bao sau biet hda cd su tang cudng

bieu hien cac gen MEF2A,MEF 2C, MEF2D va GATA4, trong bao tUang cd Desmin - mot loai protein thudc

cau true khung te bao ca, sU hinh thanh he thdng ta trung gian tren hinh anh sieu cau true te bao.

TiJf khoa: te bao gdc trung mo, 5 - azacytidine

I. DAT VAN DE

Theo quan niem cd dien, cac te^ bao cd tim

thupc loai biet hda cao va khdng khi nang phan

ehia, hinh thanh cac te bao mdi (giai doan GO).

Do vay, khi md tim bi tdn thUOng hoai td do nhdi

mau, cac te' bad cdn lai khdng cd kha nang phuc

hdi sd lifdng te bao da mat, thay the vao dd la sd

hinh thanh cac md see. Hau qua cudi cung la suy

chdc nang tim gdc. Nhdng nam gin day, lieu

phap te bao ndi len nhu mpt chien lupc diiu trj

mdi, day hda hen trong dng dung diiu trj benh If

nhdi mau cd tim, dd la sd dung nhiiu loai te bao

gdc cd ngudn gdc khac nhau nham tai tao te bao

CO tim bj tdn thifdng. Van de dat ra la loai te bao

gdc nao va phifdng phap biet hda ra sao dem lai

hieu qua cao nha't cho lieu phap nay. Cac loai te

bao gd'c vdi cac dac tfnh khac nhau da ddpc

nghien cdu v i kha nang tai tao md tim, bao gditi:

cac te' bao g6'c toan nang - pluripotent (ngudn gd'c

bao thai), te' bao gdc da nang - multipotent (cac te'

bao gdc trung m6 - MSC), va cac te bae gdc dac

hieu cua m6 tim [8]. Cd nhiiu mde dp biet hda

cua te' bao cd tim bat ngudn td cac loai te bao

gdc. Cac nghien cdu diiu kien biet hda invitro va

invivo dupc thUc hien da thu difpc ket qua kha

quan. Invitro, ket qua biet hda ddpc danh gia d

cac mde dp va bang nhieu kT thuat khac nhau. Dd

la sU bieu hien cac gen va protein dac trUng, sU

hinh thanh cac cau true sieu vi the cua te bao cP

va te bao cd tim: td ed (sarcomere), cac loai vi td

(microfilament), vi dng (microtubule), td trung gian

(intermediate filament) thupc khung te bao... va

cudi cdng la kha nang co bop tU dpng cua te bao

[9]. De tiep tuc cac nghien eUu dng dung va

nghien cdu ed ban v i MSC tai trifdng Dai hoc Y

Ha Npi, de tai nay difpc thUc hien vdi muc tieu:

1. Ap dung quy trinh sd dung 5 - azacytidine

de biet hoa MSC tiiy xaong ngadi theo hadng

tao thanh te bao ca tim. •*v *

2. Danh gia mde do thanh cong ciia qui trinh

biet hoa MSC tiiy xaang ngadi theo hadng te

bao ca tim bang 5 - azacytidine. -•:'•,•,

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