DIEN DAN Y HOC
Chuyen dk trong thang
DIEU TRI TE BAO GOC TLT THAN TlT TUY XU'ONG
CHO BENH NHAN SAU NHOI MAU CQTEM: HIEN TAI VATU'ONG LAI
Nguyen Lan Viet*, Pham Manh Hung*
TOM T A T
Phuang phap dieu tri te bao gdc dang dupe biet den nhu la sir lua chpn cd hieu qua cho nhiing benh nhan (BN) nhdi mau co tim (NMCT) cap vd suy tim. Vdi nhieu thir nghiem sir dung te bao goc tic tiiy xuong da vd dang dupe tien hanh, nhung loi ich, han che vd tdc dvmg phu tiem dn cita phuong phap dieu tri mang tinh each mang nay ciing dang duoc lam ro vd hda hen md dudng cho nhirng nghien cini lam sang vd img diing trong tuang lai.
Hien tai, hdu hit cdc thir nghiem lam sdng trong linh vuc nay deu sic dung te bao gdc tic tiiy xuong. Cdc tieu chi chinh cua cdc thic nghiem nay da sd Id an toan vd khd thi, cdc tieu chi phit cho thay hieu qua cua phuang plidp dieu Pi nay trong sira chiia ca tim sau NMCT. Can thiep vdi te bao gdc tic tiiy xuong cd ngudn gdc tir cdc te bao tuy xuong ndi sinh hoat hda vdi yeu td tdng tnrdng kich thich san xuat bach cau, hay gap la tiem te bao gdc ttr thdn tir tiiy xuong bdng each tiem vao trong ddng mach vanh hoac tiem true tiep vao ca tim. Nhirng loi ich lam sdng duoc ghi nhan la cdi thien sice co hdp ca tim vd ngdn chan qua trinh tdi cau tii'ic dm tinh thdt trdi, ke cd lam co nhd kich thude viing nhdi mau vd cdi thien tudi mau co tim d nhicng viing nay. Nhiing lgn ich lam sdng nay duoc ghi chep trong thdi gian ngdn hay trung han va dupe ghi nhan Pong cdc nghien ciru dim te bao gdc tic tuy xuong vao trong ddng mach vanh hay tiem tncc tiep vao ca tim. Cdc nhd khoa hpc gidi thich nhiing hieu qua nay Id do cdc dnh hudng gidn tiep ciia cdy te bao kit hpp vdi cdc yeu td; sir kit hap ti bao, tdi cau true thdt Pai hoac do cdc phdn img ciia cdc te bao tim gdc ndi sinh. Tuy nhien, cdc chimg cic vi tdi tao tim tao bdi ti bao gdc cdy vao cdc ti bao ca tim hay cdc ddng ti bao ca tim khde la cdn chua thuc sir dupe chimg minh day dii hoac cdn thiiu cdc dd lieu. Di lam sdng td nguy ca-lai ich cua phuang phdp diiu tii thu vi nay, cdc nghiin cuv trong tuang lai cdn tap trung vao viec xac dinh loai ti bao li tudng Pong mdi lien quan giira liiu lupng vd thdi gian cho viec siia chiia sau NMCT, phdt Piin cdc ki thuat chuyin giao ti bao, chi ra duoc nhiing ddng te bao nao la tdi uu nhdt ciing nhu biet dupe sd phdn ciia cdc ti duoc ghip la sdng sdt vd phdt huy duoc chicc ndng cdn thiet.
\. MO DAU
NMCT cap la mot the nang cua benh li mach vanh.
0 cac nude phat trien, suy tim sau NMCT la nguyen nhan chinh gay ra tir vong va tan phe. Ddi vdi cac nude dang phat trien (tiong do cd Viet Nam) NMCT cung gia tang nhanh chdng va dang trd thanh mpt tiong nhiing nguyen nhan gay tir vong hang dau [1]. Ti le tir vong sau 5 nam la 50-70% o nhiing BN da cd trieu chimg. Ddi vcii BN suy tim giai doan cudi, lira chpn de ciru sdng BN hieu qua nhat la ghep tim. Tuy nhien,
* Vien Tim Mach Viet Nam
su lira chpn nay lai rat khd khan d nhieu viing tien the gidi do cdn thieu ngudi hien tim. Chinh vi vay can mdt phuang phap dieu Ui mdi de cd the cai thien tien lupng va chat lupng cua nhirng BN sau NMCT d p . Dieu tii te bao gdc dang la lira chpn cd bieu qua cho nhirng BN suy tim sau NMCT d p [3,4]. Cac phat hien gin day cho thay cac te bao ca tim cd the tai sinh, dieu nay da thap len ngpn lira by vpng trong dieu tri suy tim sau NMCT [3]. Sau dd, cac nghien cim can lam sang va cac thu nghiem lam sang budc dau ciing cho cac ket qua iing hp phat hien tren [4, 5, 6]. Tai Viet Nam, viec nghien cim ling dung te bao gdc da cd nhirng budc di
4 I Y HOC LAM SANG S6 59 (Thang 12/2010)
Chuyen d§ trong thang
ban dau. Mdt nghien cim ciia Vien Tim mach di theo budng nay cung dang dupe tien hanh va da cd nhimg ghi nhan ban dau hira hen.
Van de dat ra la hieu qua cua phuong phap nay den dau va each tiep can nao mang lai hieu qua nhat.
Trong ndi dung bai viet nay chiing tdi mudn tdng ket lai nhiing thanh tuu bien cd trong ITnh vuc nay va nhirng hudng nghien cihi tuong lai.
II. MOT SO THLT NGHIEM LAM SANG VE DIEU TR| TE BAO GOC CHO BENH NHAN SAU NHOI MAU CO TIM CAP
Nhieu nghien ciru da va dang duoc tien hanh tai
nhidu nude nhu Diie, Bi, Dan Mach, Na Uy, Trung Qudc, My... Trong cac nghien ciru nay, ddi tupng dupe lay tiong cac nghien cim nay thudng la cae BN bi NMCT ed sdng ST eiia dien tam dd (DTD) chenh len va dupe can thiep mach vanh qua da, dat stent thanh cdng. Mpt sd nghien ciiu thuc bien tien nhiing BN da dupe phau thuat cau ndi thanh cdng. Cac BN thudng ed suy that trai vdi phan sd tdng mau tir 30-45% (binh thudng: 50-70%) va cd rdi loan van dpng viing co tim lien quan tdi NMCT gan day. Nhieu nghien ciiu tiong sd cac nghien ciru nay la mil ddi va BN duoc lay ngau nhien vao nhdm dieu trj te bao gdc va nhdm kiem soat (hau het cac trudng bap la gia dupe).
Bang 1 Thii' nghiem
(nu-o-c) FlRSTLINE-AMI'^l (Dire)
STEMMF''!
(Dan Mach) G-CSF-STEMli"i (Dire)
BOOSTi"'"!
(Diic) REPAIR-AMI (Dire)
TOPCARE-AMl (Dire)
ASTAMli'i (Nauy) Chenetali^l (Tmng qudc)
. Tom tdt mpt so thii nghi BN/chirng
15/15 39/39 22/22 30/30 102/102
29 50/50 34/35
Loai TB va lieu MNC CD34- MNC CD34- MNC CD34^
MNC 2.5X10"
MNC 2.4X10«
MNC 2.4X10^
MNC 8.7X10'
MSC 48-68X10'«
em lam sdng Thoi gian sau NMCT
1-6 1-6 1-5 6 4 3-7 5-8 18
sir dung te bdo goc tir tuy xuong
Duong ghep TB Cd djnh bang
G-CSF Cd dinh bang
G-CSF Cd dinh bang
G-CSF Bom vao DMV Bom vao DMV Bam vao DMV Bam vao DMV Bom vao DMV
Theo ddi (thang)
4&12 6 3 6 4 - 1 2
4-12 3 & 6 3 & 6
Ket qua t CO bop
tLVEF Khdng tac dung Khdng tac dung
t LVEF (+) 1 van dpng viing
t LVEF (++) t LVEF (++)
TLVEF t LVEF (+++) Ghi chu: t LVEF(-H): < 5%, ] LVEF(-H+): 5%~10%, t LVEF(+++): 10%~15%.
Cac nghien ciru td ra an toan trong thdi gian so sanh vdi nhdm dupe quan li. Cae loi ich lam sang theo ddi la 1,5 nam ma khdng cd tac dung ngoai y thu dupe la cai thien chirc nang eo bdp eiia eo tim nao dang chu y nhu bao cao trude dd, nhu tai hep va lam cham qua trinh tai edu tnic that trai. Loi ich dpng mach vanh [3-10] va rdi loan nhip [10] sau khi lam sang dupe bao cao d hon nira eac thir nghiem
S6 59 (Thang 12/2010) Y HOC LAM SANG I 5
Chuyen de trong thang
va hau bet la d cac nghien cim sir dung each tiem te bao gdc trong long dpng mach vanh/trong co tim, trong khi hieu qua eua G-CSF cdn it nhat quan. Ket qua tdt nhat cd the .xuat hien trong khoang 4-6 thang sau dieu tri. Trong 2 nghien ciiu, cho thay hieu qua se giam dan sau 12 den 18 thang sau eay ghep te bao gdc. Ndi chung, loi ich lam sang cdn chua dupe chimg minh mpt each rd net va trong mdt sd nghien eim, loi ich nay chua ben vimg theo thdi gian.
Nhimg mau thuan tiong ket qua tir eac thu nghiem gan day cho thay cd sir lien ket vdi mot vai yeu td, bao gdm: ti le ngudi trudng thanh tham gia thap, hieu qua van ehuyen te bao thap (ket thiic chi cd vai phan tram te bao di den viing nhdi mau), cd it su biet hda, va cudi cimg la do te bao ghep cd kha nang sdng sdt kem, kha nang hda nhap kem. Cae can bien (marginal) va ddi khi xuat hien nhtmg Ipi ieh lam sang dupe mang y nghla thdng ke hon la y nghia thue te \ e lam sang. Hieu qua nhu vay da dupe coi la hieu qua phu khdng lien quan true tiep vdi ngudn gde tim maeh cua cay ghep te bao. Cho den nay, cdn qua it bang chimg cho thay su biet hda eua eay ghep te bao gde tiiy xuong vao bat ky ddng te bao tim trong CO the sdng. Cd bang chimg tieh liiy do nhimg loi ich lam sang de mdi sd hieu qua, bao gdm: hieu qua can tiet, hieu qua tai tao mach, hieu qua ket hpp te bao, bieu qua co hpc thu ddng, va phan img ndi sinh cac te bao gdc tim (CSC).
III. H U d N G NGHIEN ClTU TU^ONG LAI Hien nay. cae nha khoa hpc dang tap trung vao 2 hudng nghien cim chinh:
Thu nhat: bieu dupe co che true tiep trong eay ghep te bao tren toan bd qua rim. Ndi mdt each khoa hpc. dd la each giai quyet eac \ an de nhu: sd phan eua eac te bao cay ghep Uong co the \ a tucmg tac vdi CO tim cua BN.
Thir hai: nghien ciru viec danh gia hieu qua eua lieu phap dieu tri te bao gdc trong tim mach trong
benh canh lam sang bdi sir nhan bidt va theo ddi bieu qua te bao vdi eac phuong phap chan doan hinh anh khac nhau.
1. Nghien ciru co che ciia each dieu trj te bao goc Co tim sau NMCT la mdi trudng tdng hpp, noi ma te bao gdc tim mach cd the tham gia vao viec sira chira tim. Cay ghep te bao gdc tir tiiy xuong cd the hoat hda te bao gde tim npi sinh giup ebo qua trinh sira chiia eo tim sau NMCT. Vi vay, tien eo che phirc tap eua lieu phap dieu tri te bao gdc ed the mang lai tinh mdi la eac muc tieu dieu tri tdi uu cho tai tao eo tim va mach mau. Vi du, hdn dich eua cac phan tu nhd, nhu yeu td tang trudng hay eytokin, cd the phat tiien dupe tiem va gay anh hudng tien co tim ed hoac khdng cd te bao eay ghep.
2. Nhan biet loai te bao nao la tot nhat
Viec lira chpn loai te bao thich hpp cd the lam tang hieu qua dieu tri. Bang 2 liet ke cae ngudn te bao gdc the su dung de sira chira tim. Nhin chung, te bao gdc tu than se \ an la loai te bao phii hop nhat do tinh an toan (giam kha nang phat trien thanh ung thu)
\ a tinh hda hop \ e mien djch. Trong eac ddng te bao gde ty than tir tuy xuong thi ddng bach cau don nhan phan doan td ra cd hieu qua bon. Cac ddng te bao gde trung md, te bao tuy xuong C-kit+ va te bao CD 133+ da dupe kiem chimg. Trong sd cae ddng te bao nay thi ddng te bao gdc tmng md dupe chiing minh tiem nang day hiia hen trong biet hda thanh cae loai te bao tim khac nhau trong dng nghiem va la ngudn te bao gdc kha thi, hieu qua cho viec dieu tri nhiing BN sau NMCT. Te bao gde phdi toan nang (multipotent)
\'a da nang (pluripotent) dupe tim thay d nhieu md te bao bao gdm ca tuy xucmg. Cac nghien ciiu gan day cho thay, cac te bao soma. Vi du nhu nguyen bao soi cd the dao ngupc chuong trinh trd thanh te bao gdc da nang cam (induced pluripotent stem (IPS) cells) ed tinh chat gan gidng hoac khdng the phan biet ndi khi so \ di ddng td bao gde phdi thai ve tinh chat va chirc
6 I Y HOC LAM SANG sd 59 (Thang 12/2010)
Chuyen de trong thang
4-
nang. Trong tuong lai, td bao gde da nang earn ed the thu dupe trong phdng thi nghiem va eac td bao nay se duoc cung cap cho lieu phap didu tri id bao gde.
Trong phan ldn cac trudng hpp, viec lay mpt sd lupng ldn cae te bao dac bieu yeu cau sd luong cue ldn tit tiiy xuong cua BN hoac ex vivo nhan sd luong
td bao bang each nudi cay can cd thdi gian va cd the lam m4t di eo bdi giai doan cira sd de biet hda ciia td bao. van de nay ed the vupt qua dupe bang each tiem te bao gdc true tiep vao co tim, each nay se yeu cau sd lupng te bao it hon nhung lai thu dupe hieu qua cao hon.
Bdng 2. Cdc loai te bdo chinh v&i phuong phdp te bdo goc dieu tri benh tim mach
Nguon Te bao gde tuy xuong
TBspi TB CO tim Bao thai
TenTB MSC""*
CLC<") C-kit+ cells'5'^5^'
EPC(CD133+)
(17.36)
ELC'O'"'
ipS(58,59)
CSC
ESQ60,62)
Kha nang biet hoa Multipotent (CM) Multipotent (CM) Multipotent (CM +
EC + SMC + FB) Monopotent (EC) Pluripotent (CM + EC + SMC + FB) Pluripotent (CM + EC + SMC + FB) Multipotent (CM +
EC + SMC + FB) Pluripotent (CM + EC + SMC + FB)
Ghep tu- than Cd Cd Cd Cd Cd Cd Cd Cd
Nguy CO gay ung thu
Khdng Khdng Khdng Khdng Khdng Cd Khdng Khdng
Dao thai mien djch
Khdng Khdng Khdng Khdng Khdng Khdng Khdng Khdng
Van de dao diic Khdng Khdng Khdng Khdng Khdng Khdng Khdng Khdng 3. Phat trien toi uu hoa phuong thiic van chuyen
va ghep te bao
Ve nguyen tac, mudn dieu trj bieu qua cho md te bao bi tdn thuong yeu eau dua eac te bao gdc den eang gan md bi tdn thuong eang tdt de tranh khuech tan vao cae md va co quan khac. Bd sung cai tien hieu qua cua lieu phap te bao cd the dat dupe thdng qua tdi uu hda viec phan phdi te bao. Hien tai, te bao gde dupe dua vao tim bang each tiem qua ddng mach vanh hoac tiem qua ndi mac dupe ap dung tiong cac nghien ciiu tien lam sang va cac thu nghiem tren con ngudi. Trong dd, tiem qua dpng mach vanh la phuong phap dupe sir dung phd bidn nhSt trong cac nghien cuu lam sang. Tuong tu nhu can thiep ddng mach vanh qua da, te bao gdc dupe bom vao ddng
mach vanh qua mdt catheter vdi bdng ap lire thap bom bit dau gan d nhanh ddng maeh vanh de tranh eac te bao gdc trdi ngupc trd lai. Mac du, duoc coi la mpt phuong phap an toan nhung bom te bao gde vao ddng maeh vanh eiing cd nhirng nguy ca tiem an.
Thii nhat, eac bao cao ebo thay cd sir gia tang ti le tai hep dpng mach vanh sau khi can thiep va mpt ti le cao hon cd giam luu lugng mach vanh. Thir hai, cd mpt sd lupng dang ke cae te bao gdc cu trii d nhiing CO quan khdng phai la eo quan dich.
Them nira, cd rat nhieu te bao gde khdng the den dupe vdi viing eo tim da bi nhdi mau. Phuong phap tiem te bao gdc qua dudng npi mac vao viing md eo tim tdn thuong nhd bang each tiem qua catheter duoc chi dan bdi he thdng ban do tim ludn tir tiong budng
So 59 (Thang 12/2010) Y HOC LAM SANG |
Chuyen d§ trong thang
that. Phuong phap nay dupe coi la an toan va da dugc thir nghiem tren md hinh ddng vat va mpt sd ddi tugng con ngudi. Tdm lai, viing co tim hi tdn thuong dugc khu tni bang he thdng ban do dien bpc tim, vi du nhu he thdng NOGA. Sau dd, cac te bao gdc tiem qua catheter d vi til dudng bien xung quanh vi til bj NMCT dudi su ehi dan ciia he thdng ban do. Tiem te bao gdc qua ndi mac cd the lam tang hieu qua do can sd lugng te bao it hon. Tuy nhien, eac thir nghiem lam sang ve phuong phap ndi tren cdn dang dugc tien hanh.
4. Cac thir nghiem lam sang trong tuong lai Dua tren te bao gdc, lieu phap te bao ed the cung cap cac Ipi ich lam sang dang ke nhu cae te bao gdc tuy xuong ludn cd the san xuat nhieu eytokin tai chd, do dd lam tang hieu qua siia chiia va lam lanh CO tim eiia cae yeu td can tiet (paracrine). Cae thir nghiem lam sang trong tuong lai ed the tap trung vao cac khia canh sau:
/. Dua ra eac ehi dinh tdi uu eiia lieu phap te bao gdc tu than.
2. Xac dinh dupe lieu tdi uu va thdi gian cua lieu phap te bao. Lieu tdi uu van chua duge xac dinh rd rang, trong khi thdi gian tdt nhat ciia lieu phap te bao ed the khdng bj gidi ban trong tuan dau tien ciia NMCT cap (bang 1). Hien tai, cd nhieu nghien cim lieu phap te bao ket hgp vdi bac cau ndi ehii vanh dang dugc tien hanh.
3. Giai thich va kham pha co che eiia lieu phap te bao. Nhirng cau hdi ehu chdt nhu lieu cae tac ddng ed Igi cua te bao gde duge tao ra bdi eo che can tiet hon la do tai sinh co tim, edn dang dgi cau tra loi. BOOST 11, mdt nghien ciru tien ciiu ndi tiep nghien ciiu BOOST I, nham lam sang td mdt sd van de bang each cay te bao binh thudng (tiic la te bao cd kha nang sinh sdi nay nd va ed the tiet ra eac yeu td can tiet) va eac te bao duge chieu xa (tire la cae te bao khdng the sinh sdi nay nd nhung van cd the tiet ra eac yeu td can tiet) trong nhimg benh nhan khac nhau va so sanh tac dung eua chung.
4. Tao ra cae td bao ed kha nang di ddng va lam td tdi uu. Phuang phap ghep td bao gdc qua dudng ndi mac tir tiong budng tim tao ra kha nang nham dung CO quan dich. Cae phuong phap phu tig, hoac phdi hgp vdi ghep te bao gdc edn dang dugc thir nghiem de chiing minh phuang phap nao la tdi uu. Vi du, nhu thu nghiem CELLWAVE nham xac dinh xem tioide khi dieu tri vdi viec su dung chup sieu am dan dudng vdi nang lupng thap sdng sde (ulfrasonography - guided low-energy shock waves) ed the lam tang miic dp eytokin tiong tim, muc dich lam tang kha nang lam td cua cae te bao duge tiem vao.
5. Quan li va tao hanh lang phap li cho nghien ciiu va ung dung te bao goc trong lam sang de dam bao chat luong kiem scat va an toan
Mac dii, ket qua cdn chua chac chan, cae nghien cim va phat trien tiong ling dung te bao gdc tien toan the gidi dang phat trien rat nhanh tien tdi eac img dung lam sang. Hien tai, cd gan 50 cudc thir nghiem lam sang da duge dang ky tien tiang web CliniealTrials.gov. Tmdc khi ap dung mot each an toan cho BN, cae te bao gdc tir tuy xuong can phai duge each li va xir li tiong phdng thi nghiem. Trong khi tao ra cac ddng bach eau don nhan tir te bao gdc tiiy xuong chi mat cd vai gid, thi thdi gian chuan bi cho ddng te bao gdc tmng md, ddng bach cau don nhan phan doan cd the mat den 3 tuan (til phan lap den nhan sd luong va biet hda). Nhu vay, ap dung cae te bao gde ed ngudn gdc tir tiiy xuong cho BN la mdt qua trinh phiic tap bat dau tir phdng md, sau dd di chuyen den phdng thi nghiem va cudi eiing tid lai phdng md hoac don vi tim mach can thiep. Trong thuc hanh lam sang ngay nay, qua trinh nay phai tuan thii tieu chuan thuc hanh san xuat tdt (GMP) de lam giam nii ro ddi vdi BN. Theo do, lieu phap te bao tinng tam cd kha nang se dugc GMP cdng nhan, tiong dd nhan vien se dugc dao tao theo cac chuan eiia GMP de hp ed the boat ddng trong cac eo sd cu the (phdng sach va cae eo sd nudi eay te bao trong phdng thi nghiem).
Tuong Ur, viec tidn hanh lieu phap te bao gdc tao huyet
8 I Y HOC L A M S A N G S6 59 (Thang 12/2010)
Chuyen d§ trong thang
dupe thdng qua tai nhidu benh vien Uen loan the gidi.
Thao tac vdi cae te bao nhan vien y te ed the vd tinh tiep xiic vdi te bao con ngudi vdi nhieu mdi nguy hiem va nhiem ban. Van dd quan tam nhat la nhiem ki sinh triing, ngudn gde tir nguyen lieu lay hi ddng vat (nhu bao thai be hoac huyet thanh bd) thudng dugc su dung trong nudi eay te bao. Van de nay ed the dugc khac phuc bang each sir dung mdi tmong huyet thanh tu do sEn ed (vdi eac yeu td tang tmdng bd sung). Trong khi chd dpi, huyet thanh tu than ed the thay the cho huyet thanh ddng vat. Cudi eiing, ttudc khi dugc dung cho BN, cae te bao phai dugc kiem tra tinh nhiem khuan vao cac thdi diem khac nhau, vdi nhimg protocol rieng biet (VD: Nhudm Gram)
IV. KET LUAN
Nhirng mong mdi eiia lieu phap te bao gde la de tai tao eau tnic va chiic nang co tim thdng qua qua trinh tai tao CO tim va tai tao mach, de cai thien tien lugng va chat lupng cupc sdng cho ngudi benh tim maeh. Tuy vay, bieu qua va nhimg mong mdi nay van dang duge chimg minh thdng qua cac nghien ciiu va bien nay lieu phap nay van chua dugc khuyen cao trong thue hanh thudng quy tien lam sang. Can cd nhiing nghien eiiu CO ban sau hon vdi nhung hieu biet rd hon ve co che
ciia lieu phap te bao gdc trong eac benh canh lam sang khac nhau va phai dugc chimg minh thdng qua cac thir nghiem lam sang vdi thiet ke chat che, cae te bao se duge theo ddi va ehup hinh, ben canh dd cac bien phap danh gia gian tiep thdng qua cae chan doan binh anh nhu danh gia chirc nang cac budng tim ciing ddng vai tid rat quan tipng. Cdn kha nhieu thach thiic va cau hdi can giai dap cho lieu phap nay nhu: chi dinh (ddi tugng BN) nao la tdi uu, thdi gian sau NMCT, loai te bao nao, sd lugng te bao, dudng ghep, chat dan (vector) va nguy CO lau dai (ung thu)...?
Chiing ta lac quan va tin tudng vao tiem nang to ldn ciia lieu phap te bao gdc tiong dieu in cac benh tim maeh. Tuy nhien, chi cho tdi khi cd cac bang chimg, nghien eim xac dang ung hg hieu qua phuong phap dieu tri te bao gdc ehiing ta mdi cd the ap dung vao trong dieu tri thudng quy trong thuc hanh lam sang. Do vay, chiing ta nen tiep tue tap trung cac nghien eiiu, nang cao kien thiic va gdp phan chuyen dich tir hieu biet den thuc hanh de lam sang td nhung van de edn phiic tap va cdn ban cai cua phuong phap dieu tij te bao gdc tiong benh li tim mach. Tuong lai tuoi sang dang d phia trude, nhung con dudng di tdi tuong lai khdng chi ed tham do va hoa hdng.
TAI LIEU THAM KHAO
1. Nguyin Ldn Viet, Pham Viet Tuan, Pham Manh Himg, Vdn Dice Hanh. 'Nghien ciru md hinh benh tim mach tai Vien Tim Mach" - Benh Viin Bach Mai tic 2003-2007. Tap chi Tim mach hpc Viet Nam, 51, 2010.
2. Braunwald E. Shattuck "Lecture- cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities ".
NEnglJMed 1997; 337: 1360-9.
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SUMMARY
STEM CELL THERAPY FOR PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: PRESENT AND FUTURE
Stem cell-based cell therapy has emerged as a potentially therapeutic option for patients with acute myocardial infarction (AMI) and heart failure. With the completion of a number of tiials using bone marrow (BM)-denved adult stem cells, critical examination of the overall clinical benefits, limitations and potential side effects of this revohitionaiy treatment will pave the wayforfuture clinical research. At present clinical trials have been conducted almost exclusively using BM stem cells. The primaiy endpoints of these trials are mainly safet\' and feasibility.with secondary endpoints in the efficacy of post-myocardial infarction (MI) cardiac repair Intervention with BM-derived cells was mainly carried out by endogenously-mobilised BM cells with granulocyte-colony stimulating factor, and more frequently, by intracoronaiy infusion or direct intramyocardial injection of autologous BM cells. Wliile these studies have been proven safe and feasible without notable side effects, mixed outcomes in terms of clinical benefits have been reported. The major clinical benefits obsened are improved cardiac
contractile function and suppressed left venPieular negative remodelling, including reduced infarct size and improved cardiac peifusion of infarct zone. Moderate and transient clinical benefits have been mostly obsei'ved in studies with intracoronary infusion or direct intramyocardial injection of BM cells. These effects are widely considered to be indirect effects of implanted cells in association with paracrine factors, cell fusion, passive venPieular remodelling, or the responses of endogenous caidiac stem cells. In contrast, evidence of cardiac regeneration characterised by differentiation of implanted stem cells into cardiomyocytes and other cardiac cell lineages, is weak or lacking. To elucidate a clear risk-benefit of this exciting therapy, future studies on the mechanisms of cardiac cell therapy will need to focus on confirming the ideal cell types in relation to dosage and timing for post-M cardiac repair, developing more effective cell delivery techniques, and devising innovative cell ti'acking modalities that could unveil the fates of implanted cells such as survival, engraftment and functionality.
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