NGHIGN C L / U - T R R O D O I
TE BAO GOC: XU THE VA DjNH HUdNG ONG DUNG
TS N G U Y I N BIJfC THAI TO cac Ihanh ttfu lo Ifln ve tg' bao g8'c (TBG), nhSng nam gan flay da hinh thanh mot cong nghe mSi trong y hgc vfii rS't nhilu tiem nang iJng dung quan trong va gia trj kinh te'ifln lao. Mac du dang co nhieu rao can va han che', song ldi td'c tilf cong nghe TBG vin dddc dd doan la se sanh ngang vdl cac nganh dien tiif, internet, cong nghe phSn mem, vdi doanh thu hang tram ty USD. Bai viet phan tfch sd phat trien cua cdng nghe TBG, tiem nang va gidi han hien tai cua TBG, cung nhdng gdi y ve dng dgng, phat trien cong nghe nay tai Viet Nam.
Tir khoa: te'bao gd'c.
6TEM CELL: TDEND AND ODIESTATION OF
APPUCATION 5j?Tna-y Advances in stem cell research worldwide in the recent years have established a paradigm shift in medical research with a-great potential of Important applications as well as economic values. Although there remain various technical limitation and restricted regulation, the expected outcomes from stem cell applications are huge and comparable to other hi-tech industries including electronics, internet, softwares with the revenue ot multibillion USDs.
This article analyses the market potentials and recent progresses of stem cell research as well as its limitations; subsequently, the author suggests strategic plans for its development and application in Vietnam.
Keyword: stem celL
TBG: Iru cot thiif 4 c u a y t e
Ta nhdng dng dung khiem tdn dung TBG mau ngoai vi, cudng I rdn va tuy xadng trong nhieng nam 60-70 cija the ky trade, sd hinh I thanh va phat tnen cua cong nghe sinh hoc gom te bao hoc, sinh hpc phan ti^, di truyen hgc da thuc day cac nghien cdu TBG dat dapc cac thanh tau ngoan muc. TBG phdi dau tien cua James Thompson da dadc cdng bo nam 1998, va trade dd mpt nam, TBG ung tha da ddpc nhan dien. Tiep theo la cac TBG trddng thanh dddc nghien cdu cho j tri iieu benh tim mach, tieu dddng, than kinh (2000); TBG trung mo l (mesenchymal stem cell - MSG) da dddc thi!f nghiem lam sang cho I nhieu benh (2008); TBG cam bien IPS (induced pluripolent stem cell)
"; dddc kham pha nam 2006 va dogt giai Nobel nam 2012 vdi tiem nang I trj lieu ca the va nhieu dng dung quan trong khac. Hang loat TBG mdi I cung da ddpc phat hien td nhieu nguon vdi tiem nang trj cac benh man tfnh hiem ngheo. Trong cdng nghe nudi cay tang phu, TBG da
•-• dddc dung tao thanh cdng qua tim ngadi trong dpng vat (heo); cong I nghe in 3D cung dddc dung tao cac dong TBG thanh tang phi!i nhU I gan, vong mac (2013). Cac kham pha mdi ve TBG dang diln bien lien ' tuc hang ngay va rat sinh ddng d nhieu ndi tren the gidi.
Nhdng tien bg neu tren va tiem nang dng dung tri lieu ldn lao cua TBG da tao cho cong nghe nay mdt vi the rat dac thu trong he thong y te ngay nay. Theo cac chuyen gia, trj lieu TBG trong tddng lai se 1^
phan thiet yeu cua nganh Te bao tri lieu cua nen y te the gidi. Theo dd, TBG dang hinh thanh cong nghe tri lieu cot tru thd 4 va cung la cdt try CUOI cung, vi cdng nghe TBG cd kha nang bd sung va hoan thidn 3 cong nghe y te nen tang dd la: hoa dapc, sinh dapc va thiet bj y t l . Ve ky thuat, cdng nghe TBG siir dung te bao nen rat khac biet vdi 3 cdng nghe tren, ke ca cong nghe sinh dapc ma nen tang la sinh hpc phan td. Muc tieu cua TBG di xa hpn cac tri lieu khac, phapng ph^p TBG nham tn lieu tnet de td kha nang thay the cac te bdo ha hdng
38 TapcNKHOAHQf CONG NGHE VIET NAM
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thay vi siia chOa chung trong nhiing phddng phap trj lieu truyin thdng.
Dfng dung va gia tri kinh te cna cong nghe TBG
Vdi nhflng tien trien ve khoa hpc ky thuat cua TBG nhd da neu, hidn cd r^t nhieu hogt dpng va hadng d i u ta. Trong dd cd nhflng hddng tieu bieu sau: thay ddi hoan toan td bao hd hdng, mang lai dilu trj toan didn; bd khuyet chdc nang hd hdng cua t l bao d l giam thieu benh ly; tgo cd quan, tgng phD; phong va chdng ung thd; sdng Ipc va nghidn cdu thudc; djch vu ngan hang TBG; tham my; bao vd cd t h i khdi mdi tradng ddc hgi; mien dich tri lieu;
chuyen tai gen cho trj lieu; cay ghep ddng hoac dj dgng; hd trp sinh skn; nhdn ban ddng vat; tao dgng vat ohuyin gen; d i u an sinh hpc.
Hien tgi, vide dng dung va kinh doanh TBG khdng ddng deu tren the gidi. Theo nghien cdu cua Transparency Market Research, thj tradng TBG todn c l u dat khoang 25 ty USD vao nam 2011 va se tang len mdc tren 100 ty USD vao nam 2018.
Tdc dO tang tradng mgnh me nay chu yeu xuat phat td sy bung nd oac djch vy trj benh bang TBG tai dia phapng hoac qua cac chUdng trinh du Ijch y te (medical tourism) thadng dat trung tam d cac qud'c gia dang phdt triln.
Tuy vay, 6 My va chau Au, doanh thu td cac djch vy trj lidu TBG odn gidi hgn do nhieu rao ckn phap ly. Phin Idn nhflng san pham kinh doanh TBG danh cho nghidn odu nha da'u an sinh hpc va mot sd djch vy tgo cac ddng TBG cho nghien cdu. V l trj lieu, ldi tdc kinh doanh chinh la td cac Scin pham cho trj lieu ngoai da ho§c cho xddng khdp. 6 chau Au, con sd nay la trdn 800 trieu USD nam 2011 va dy bao dgt 1,5 ty USD nam 2016; cac sdn pham tgo td TBG d chau A va nhflng nddc khac cung cdn gidi han vd tadng dddng nhd chau Au (hinh 1).
Hinh 1 in gii kinh tff TBG tr6n thg gidi vi diJ doin tdi nim 2016
Nghien cdu thadng khdng ddpc coi la nganh kinh doanh, nhang trong nhieu tradng hdp, sd phat then cdc cdng nghe tiem ndng nha TBG cd the mang Igi nhflng ldi nhuan ddng ke cho cac trddng dgi hpc hoac vidn nghien cau. Trong sd hPn 3 ty USD dau tu oho nghien cdu TBG d tieu bang California (My), Dai hoc California da thu ve hang tram trieu USD ldi nhuan, tieu bang California cung thu dddc mot sd tien thue Idn. 6 mdi trddng hep hdn, cdc phdng thi nghiem TBG cd the nhan ddpc nhdng hpp ddng cho djch vu hoac san pham tfl cac hang dddc ldn, vi qua sa dau ta nay hg se giam thieu ddpc chi phi nghien cdu.
Quan niem ve an toan cho trj lieu TBG cua cdc nddc dang phat then thudng ddn gian vd lieu phap TBG dapc coi nha te bao mau, djch tuy, hoac tgng phu cd t h i dapc truyen ghep ta ngadi manh khoe cho ngadi benh. Truyen TBG cd the thac hien qua dich vy y te (medical service) d cac benh vien, va qua cdch lam nay hp da tranh ne dddc mot sd rao can phap ly. Phddng phap ghep TBG ta than thdng dyng d nhflng nddc dang phat triln da tao ra cdng nghe du hch y te hang nhieu trieu USD. Nhieu benh vien va trung tam y te dau td vao cdc tien nghi ha tang cd sd va cd khd nang thu hut benh nhan Xii ck nhflng nddc phdt trien. Vl phan Idn khdng cd nhflng nghien cflu khoa hgc d cac trung tam ndy, nen thadng cd nhieu tranh cai ve ket qud trj lieu; cac td chdc qude te nha ISSCR (International Society for Stem Cell Research) Id ngudn thdng tin hflu fch de Chung ta ddi chieu.
Trai lai, My va cdc nddc phdt trien cd mdt dinh nghTa rat chat che ve TBG vd xep vao danh muc
"Ddpc pham" (Drug). Nhin chung d cac nddc nay, dng dung trj lieu dung TBG cdn nhieu gidi ban; TBG cudng ron vd tuy xddng td nhieu nam nay vSn la ngudn TBG chinh cho cao tri lieu ghep dong dang hay dj dgng. Trong cac TBG trddng thanh, TBG trung md (MSC) ed rat nhieu tiem nang, an toan trong nhflng thd nghiem lam sang va mot so dapc cap phep san xuat ang dung tren thi tradng. Tieu bieu Id Prochymal cua Osiris Therapeutics Inc., My. Day la san pham TBG dau tien tren the gidi dapc Cd quan y te' quoc gia Canada va New Zealand cap giay phep dung cho bie'n chdng trong trddng hpp ghep tang phu (_thadng dapc gpi Id GvHD), do khd nSng dc che mien djch, chdng viem. Cac thd nghiem cho kha nang tai tao ciJa Prochymal de chQa cac b$nh nhd tim mach, nghen hd hap mgn tinh (COPD), chda dgt ket qua mong muon. Prochymal da dapc
CA17 ^™,oni^ TapcHKHOAHQC 39 So17nam2014 _i,,_.T_„_,_i._ . . A J -
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NGHIGN COU-TRHO BOI
Osiris chuyen giao cho hang Mesoblast nam 2013 vdi tri gia 100 trieu USD. Mdt so san pham TBG khac dddc cap ptiep gdm: Hemacoid, LaViv (My), CartiStem, Cellgram, HeartiCeliGram {Hdn Quoc).
Vi TBG ddpc dmh nghTa ia ddpc pham, nen san xuat va SLf dyng TBG phai tuan thu theo quy dmh nghiem ngat cua Cd quan y te va thdc pham My (FDA), trade khi cd the thadng mgi hod. Theo dd, cdc TBG can qua it nhat 3 giai doan thd nghiem, gdm pha 1 (thir dp an toan cua thudc tren so it ddi tddng - khodng dadi 10 ngadi), pha 2 (thd dp an todn va hieu nang tren ddi tddng vai chyc den vai tram) va pha 3 (thfl nghiem an toan va hieu nang tren sd ddi tddng benh nhan Idn va da dgng, cd t h i vai nghin ngddi). Thdi gian cija cdc thd nghiem nay cd the td 7-10 nam. Tren thac te, TBG can ddpc kiem tra chat che hdn cac ddpo pham cd ngudn gd'c hod hpc vi ban chat sinh hpc phdc tgp cua TBG va kha nang sinh tdn lau dai trong cd the (khdng bj chuyen hoa va dao thai nha hoa dapc). Chfnh sd chda hoan toan kiem soat ddpc ban tinh phac tap cCia TBG la nguyen nhan cija sa than trong neu tren.
Tuy nhien, dang hinh thanh mdt sd td chac da qude gia nha International Cell Medicine Society (ICMS) tranh dau oho mdt cd che phap ly de cd the dng dung TBG cho mot sd tri lieu can thid't. G i n day nha't, tieu bang Calorado ban hanh luat "Cho dung thudc thd nghiem" (Right to Try) dang md ra mpt canh cda cho viec sis dung TBG de tn lieu nhOng benh nhan mac cac benh hiem ngheo ma cac tri lieu khac khdng hieu nghiem. Cd the trong tddng lai cac lugt Id y te se kiem soat TBG theo nhflng nguyen t i c linh dpng va da dang dda tren dac tinh sinh hpc cCia te bao, thay vi dda tren mo hinh thd nghiem thudc nhd hien nay khdng dung tieu chuan cho TBG va gdy sd tri hoan.
NhiTng gidi h a n ciia TBG
Truyen thdng thadng "tung hd" ve cac ke't qua
"tdt dep" cua TBG khi TBG ddpc dung trj lieu oho rat nhieu benh ly,tflddn gian nha tham my ngoai da cho den cdo benh hiem ngheo nha ung tha, tieu dddng, nghen hd hap, than kinh... (cd khoang 70 loai benh cd the dapc trj bang TBG). Song cac thdng tin ndy cung mang Igi nhieu thlc mac, vi tren thac te nhflng dng dung TBG thadng khdng dapc cap giay phep, hoac bi dinh cht va cam doan. Nhflng gidi hgn dng dyng cija TBG tuy thudc vao rat nhieu ly do, trong dd cd cac ly do chinh:
- Thay ddi ban chat sinh hpc cua TBG trong tien
trinh nudi cay va biet hod 6 phdng thf nghidm. Mpt sd te bao cd the sinh khang nguydn khang lai benh nhan, va quan trgng hdn la mgt sd cd dot biln gen vdi tiem nang gay ung thd.
- Ve mat ky thuat, quan the TBG khi dadc biet hoa thadng khdng ddng nhat. Trong trddng hpp biet hoa TBG phdi, si/ lay nhilm cua TBG phdi cd the tao ung budu trong ky chij.
- Bao quan khd khan vi dd ben cda TBG hoac te bao biet hod thddng tha'p, ngoai ra khd nang lay nhiem vi, sieu vi cao hdn cac san pham hoa hoac sinh dddc.
V l mat san xuat TBG, dgc bidt TBG trddng thanh, cd ton phf rat cao va thddng gidi hgn trong viec tao sd lapng can thiet cho nhieu logi benh.
- Ve mat sii dung, khac vdi cdc loai thudc, rit kho mang TBG den dich trj lieu va theo ddi diln biln, chuyen hoa chat.
Hien cd ra't nhieu loai TBG khac nhau, dddc lay trdc tiep ta cac cd quan cCia ngadi. 6 mdi cd quan cd vung d (nitch) TBG va dd Id TBG trddng thanh mang ten tgng phij nha TBG tim, tuy, thin kinh...
Hoac tfl phdng thf nghiem, TBG phdi dddc liy til phdi bao (blastocyte) nudi cay trong hd trp sinh sdn;
vdi tien bp cua khoa hpc, ky thuat TBG da ddpc tgo thdnh do chuyen nhan (SCNT), hoac cac gen bilt hoa de tgo TBG iPS (hinh 2 va 3).
" ^ • - .
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Hinh 2: mdt sd nguon TBG tLf ngUdi
Hinh 3: cic ngudn TBG to phdng thi nghiim
TBG phdi: cd tfnh van nang, tao ra dddc mpi logi te bao, nhdng da cd nhieu trd ngai trong vide dng dung trj lieu, gdm ca khia egnh ky thuat va dao ddc.
Geron Id hang dau tien d My dddc phep dung TBG phdi cho chan thddng cot sd'ng nam 2009, nhdng da bo eudc 2 ndm sau dd vi bdn tinh phdc tgp cua te bao phdi. TBG phdi cung thddng dddc dung de nghien cdu chfla tri nhflng benh cua nao bd vl TBG than kinh rat hiem va khd phdn lap, tuy nhidn dng dung TBG phdi cd ty le gay ung thd cao (5% khi
40 T « ? P f ^ K « 9 ' i H f ^ So 17 nam 2014
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dddc thii nghidm 6 chupt). Da cd tradng hpp cdu be ngddi Israel dddc tiem TBG phdi vao nao nam 2001 de trj chdng benh di truyen, 4 nam sau, khi kilm tra, cac bac sT thupc Trung tam Y te Sheba d Tel Aviv da phat hien khdi u trong nao va trong tCiy sdng. Tuy nhien vi tiem nang Idn lao, TBG phdi hien ddpc nghien cflu sdu rpng d nhieu trung tam dgi hpc uy tin.
TBG ciim bi^n IPS: TBG cam biln iPS (induced pluripotent stem ceil) dang md ra mdt hddng di mdi cho cdng nghe TBG vdi nhilu ky vgng Idn lao. iPS ddpc tgo tfl cac te bao binh thadng nha da cua ngadi benh qua phUdng phap ehuyen gen nham tri lieu ea t h i . Tuy nhien, chda the tien lieu ddpc mdc dp kha thi cho nhflng flng dung ci!ia iPS vi cdn nhieu van d l can khac phue, dgo biet ve tinh an toan va hieu nang. IPS ddpc biet hoa bang gen, trong dd hai gen cMyc va Klf4 cd khd ndng gay ung tha cho khoang 20% sd chudt thfl nghiem, ngoai ra cae sieu vi dung chuyin hoa gen cung cd khd nang iam thay ddi bd gen cija te bao vdi nhflng ohflo nang khong ladng ddpc (hinh 4). Mpt sd nghien cflu nhlm tranh tac ddng gay ung thd cua iPS gdm: dung protein tai td hpp de biet hoa thay eho cae virus hoac khdng ddng cMyc, klf4; iPS cd the dddc tao thanh bang gen khdng ung thd F0XH1; IPS biet hoa thanh megakaryocyte (tao tieu cau) khdng cd khd nang gdy ung tha vi cac t l bao nay khong cd nhan. Cac nghien cflu gan day cho thay, iPS khdng thdc sa cd tfnh toan nang nhd TBG phoi, khi so sanh tfnh methyl hoa bp gen cua IPS cho thay iPS cd khac bidt nhilu hdn so vdi TBG phdi. IPS hieu qud hPn khi ddpc tdi biet hoa thanh te bao nguyen thuj", thay vi cac ddng td' bao khac. Ngoai ra, te bao biet hoa td IPS cd tudi thp thap hdn t l bdo binh thadng.
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Hinh 4: quy trinh t$o TBG iPS td tS bio da (2 yiu t6 c-Myc vi Klf4 li chit tgo ddng ti bio ung thU)
Ngoai th lieu cd the, nhdm cua Yamanaka ky vpng cd the tgo IPS cd flng dyng cho mdt sd ldn bdnh nhdn qua chgn Ipc ddng te bao cd he bieu thi he khang nguyen (HLA) thap nhat nham tranh dao thai miln djch. Phddng phap tgo iPS cung ddpc nghien cflu thanh cdng tgo cac te bao mdu thanh te bdo cdm flng mau (IHSC - induced hematopoetic stem cell), va se mang lai flng dung rat quan trpng de dap flng nhu eau thieu ngudn tiep lieu mau cho cap cdu, cac benh ung tha, thilu mau do xa trj va nhieu nguyen do khac. Nhat Ban va nhilu trung tam nghien cflu cua the gidi dang dau td rat Idn (hang tram trieu USD) vao cdc chadng trinh nghien cflu IPS vdi mye tieu khae phuc nhflng khd khan va khai thdc tiem nang cua iPS de nhanh chdng dda vao flng dung, trj lidu.
TBG tuy xuang, TBG cuong ron: eung nhd TBG tuy xddng, TBG cudng rdn cd dp an toan cao, viec danh gia he khang nguyen ddn gian hdn TBG tuy xddng, nen la ngudn dddc da chudng. Tuy nhien, hieu nang trj lieu cija TBG cudng rdn gidi ban vi tfnh biet hoa khdng cao, nhOng benh di truyen cCia ngddi eho chaa bieu hien nen thadng khdng dapc biet.
TBG trudng thknh: dd cd nhilu ky vpng cho flng dung vi cd dp an toan hdn TBG phdi vd da cd mdt so tien bp ddng ke. Biet hoa TBG tim da cd ddpc nhOng thfl nghiem ldm sang an toan, hieu nang cao eho viee hdi phuc benh nhdi mau cd tim. Tuy nhien, cdn rat nhieu trd nggi ddi vdi TBG tuy cho benh dai thao dddng va TBG than kinh cho cae benh ve tdn thadng nao bd hoac mat tri nhd d tudi gia. Phan Idn cdc TBG nay khi biet hoa khdng tgo ddpc tap t h i t l bao thuan chung va cd tinh on djnh cao d l ditng trj lieu nhd tieu chuan cua dapc pham.
Cac loai TBG khdc nha TBG md md {ADSC- adipocyte stem cell), TBG trung md td ra ft khuyet diem hdn va dang ddpc nghien cflu dng dung rdng rai (xem phan dadi). TBG ung thd (dapc xem la te bao cdt Idi gay cac benh ung tha va di can, cd tinh khang thudc cao) hien dang ddpc nghien cflu ehuyen sau de hieu biet ve ung thfl va tim kiem eac phddng phap tri lieu mdi.
Tim mot htfofng di cho Viet Nam
Vdi tiem nang dng dung Idn lao cua TBG cho nganh y te vacdng nghe dapc pham, cac nadc trdn the' gidi da nhanh chdng lap nhflng chiln lapc mui nhpn cho viec nghien cflu va tnen khai TBG, 6 My, tuy chfnh phCi lien bang cdn nhflng rang budc v l lugt le, nhflng da danh cho cdc tilu bang nhilu ty do triln khai TBG. Nhat Bdn la nadc thadng mua
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Igi ban quyin hoac lien k i t dau ta vdi My va chdu Au d l phat trien cac ket qua nghidn cflu thanh san pham thfldng mai, nhang hp da hoan toan thay ddi chiln lapc oho TBG, khi Yamanaka tgo thanh cdng TBG iPS. Chfnh phd Nhat Ban da ddu ta gan nda ty USD xay dyng Trung tam Nghien cflu IPS nham thuc day nhanh cdng nghe ndy tdi dng dyng. Cac nddc Han Qude, Trung Qud'c cung khdng bd 16 eudc dua nhieu Ipi fch nay.
Nhflng diln tien sdi ndi ve phat then TBG dang tao cho cpng ddng TBG Viet Nam nhilu cP hpi va nhflng thii thach. Cho den nay, hau het cac ddng TBG khdng dddc sfl dung trj lieu ma ehi dddc dung rat gidi hgn trong cac thfl nghiem iam sang, dae bidt la TBG phdi, TBG thupc logi chuyen nhan (SCNT) hoac chuyen gen (IPS). Cdc dong TBG trddng tharih biet hoa d mdi tradng thi nghiem cung bj ra't nhieu hgn ohe. Tuy nhien, ta mdt sd san pham TBG dapc cap phep vd trj lieu thanh cdng g i n day, da mang lgi nhflng cd hpi mdi cho viec phat trien cdng nghe TBG 6 nhieu ndi. 6 Viet Nam, trong thdi gian 2-3 nam qua, mdt sd cd sd nghien cflu TBG da thdm dd va tdng bfldo trien khai eae flng dung TBG eho trj lieu dda theo cdng nghe mdi. Phdng thi nghidm TBG thupc Trddng Dgi hpc Khoa hpc Tfl nhien (Dgi hpc Qud'c gia TP Hd Chi Minh) dang tgo dddc mdt so ky thugt tieu chuan nhd tao ddng TBG trung md, TBG md md oho eae flng dyng trj lieu vd TBG ung tha cho nghien cau chuyen sau. Ngoai ra, ciJng da cd khuynh hadng cdc chuyen gia TBG trd ve tfl nfldo ngodi nhfl TS Nguyen Van Thuan tfl Han Qud'c (hien lam viec tgi Trung tam Hd trp sinh san - IVF, Dai hoc Tan tao). Tfl lau, flng dung TBG mdu eudng rdn da ddpc trien khai rat sdm (vao nhflng nam 90) tgi nhieu od sd nha Trung tam huyet hpe, vien bong, vien nhi, benh vien nhan khoa va quan y. Gan day, song song vdi nghien cdu va chuyen giao cdng nghe, mdt sd cdng ty TBG da hinh thdnh nha Mekophar, GeneWorld, FBM (TP Hd Chf Minh);
Cdng ty Cdng nghe sinh hpo Tri Phadc (Hd Ndi).
Vide cac nhdm chuyen gia TBG d TP Hd Chi Minh gan ddy djnh ky td chflc cac budi thao luan ve TBG la mpt sinh hoat khoa hpc cd y nghTa va can dapc khuyen khfoh md rdng.
Vi nhilu van de cua TBG ma khoa hpc ngay nay ohfla dapc hoan todn thdng sudt, Viet Nam nen du tien oho cdc flng dyng cd dp an toan eao, cd tinh thdc tien, tdn phi gidi han, trong dd cd cdc hadng sau:
Trien khai tri lieu TBG bing phUdng phap tt/ thBn, tri/c tiep va khdng can thiep: phapng phap nay dung
TBG cua benh nhan, truyen trUc tiep va khdng bigt hoa hay nudi cay trong phdng thi nghidm, ndn co dd an todn cao. Phan Idn phddng phap TBG tfl thdn diiing TBG md md va nhflng thao tac cd bdn ndn chi phi thdp.
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Hinh 5: cac giai doan in lidu dung TBG md md S W F 1^ p h a n k&t t y c u a m o m e g 6 m T B G vS n h i e u loai tS b a o k h ^ c cCing c ^ c ySu t o t a n g trLfSng
S V F
Hinh 6: SVF ii sin phim TBG (phin chfnh ii TBG trung md - MSC) va tap chit lay tCr md md binh nhin Hinh 5 va 6 md ta cac bade ky thuat thu nhdn TBG tfl md md dung cho trj lieu. Tuy dPn gian, nhdng flng dyng TBG mo md ddi hdi cac phddng phdp xul ly linh ddng va than trpng. Theo dd, md can dddc loai bd hodn toan de tranh gay nghen mgch mdu, hoac nghen phdi do sd Iflpng ldn TBG dfldc truyin.
Tuy trddng hdp cd the dung protein TBG (stem cell extract) thay eho TBG hoac dung TBG tang sinh (stem cell expansion) de dgt ket qud tdi du. Vi TBG cd tfnh kich thich tang tradng mgnh eac te bao, bgnh nhan dang chfla trj ung thfl can dydc td v i n danh gia ky ladng trade khi thac hien. Tren thflc t l , hi$u nang cilia TBG md md thd'p va tae dyng cham, cdc thude cytokines kich thfch va tac dpng vao he miln djch, chd'ng viem cd the giup gia tdng hidu nang cOa TBG. Ngoai ra, k i t hpp vdi phfldng phap chfla trj khac, ke cd Ddng y, cung ddpc mdt sd ndi flng dyng va dgt hieu qud trj lidu cao hdn. Hien nay, phddng phap td than dddc dung dieu trj clio mdt sd b^nh gdm khdp gdi, nghen phdi man tinh (COPD), vilm ruot, thodi hoa than kinh.
42 , TapcHKHOAHM So 17 nam 2014 CONG NGHE VIET NlUir
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Qua quan sat va danh gia, chung tdi nhgn thay phddng phap dung TBG ta than an toan va da cd nhflng ket qud kha quan giup giam thieu benh hoac cd trfldng hpp ldnh benh. VI chaa cd tieu chuan (nha FDA) cho cac tn lieu dung TBG hien nay, cdc ket qua se thay ddi tuy theo phddng phap va kinh nghiem thyc hanh cfla nhdm trj lieu. Cho nen trong ke hogeh thdc hien, viec hpp tdc vdi nhflng trung tam cd tieu chuan khoa hpc eao va thanh tfeh tdt la yeu td rat quan trpng va can thilt.
Lfng dijng TBG sang loc duac lieu (Drug Screening):
flng dyng TBG thfl nghiem tiln iam sang dang la mdt cd hdi mdi cho kinh doanh. Thfl nghiem thudc chiem gan 70% chi tieu nghien cflu thudc d cac cdng ty dapc ldn. 6 Viet Nam, thfl nghiem dpe tinh va hieu ndng thudc dung TBG la mdt thj tradng cdn bo ngd va cd tilm ndng ldn cho khoa hpc vd kinh t l . Cdc ddng TBG phdi va IPS la ngudn quan trgng de chung ta thyc hien oao chadng trinh danh gia tim kiem dapc pham Xis cac ngudn trong nadc hay lam djch vu tfl cac cdng ty da qude gia. Vdi ngudn ddpc thao rat phong phu d Viet Nam, TBG dang tgo mot OP hdi de chung ta ddnh gia va tim kilm nhilu boat chat tn lieu gia tri.
Trong dd, ehung ta can ed kha ndng: nudi cay va duy tri mot sd Iflpng Idn TBG bang oaoh khai trien cdng nghd sdn xult cac protein tang sinh d l gidm chi phf, vi cac protein nay cd tdn phi rat cao theo gid ngoai nhap; tim kiem ddpc thdo cd tao dyng tang sinh TBG se la mdt kham phd cd gia trj Idn v l tri lieu oung nha kinh t l ; thie't lap he thd'ng ta dpng cd kha nang dd tim va danh gia tac dung mot sd Idpng Idn dddc thao hoac hod chat tren TBG. Ty Id tim dddc thudc cd tac dyng thadng la rat thap nen can cd he thdng^ty ddng de sang loc hang ngan dapo oha'tva mdu pham trong cac thfl nghiem. Qua kinh nghiem lam vide d mdt sd trung tam nghien cflu trong nddc, chung tdi nhan thay dilu nay hoan toan kha thi, neu chung ta kit hpp cac nhdm ehuyen ngdnh ve ky thuat cd khf, ty ddng de cung thao hien.
Tgo t^ng phu (Tissue Englnering): ndm 2012, TS Hire Nakauchi cua Dgi hpe Tokyo da edng bd thanh tyu tgo dapc qua tim ngadi tfl viec dung TBG ngadi dapc bidt hoa thanh tim trong heo, md ra mot bade tiln ddn vide san xuat tim ngadi va nhieu tang phu khac. Trade dd, viee tgo qud tim tfl TBG cd kha nang CO bdp trdn gia the cung la bfldc dot pha cho cdng ngh$ TBG tgo tgng phu. Cdng nghe nay dang dapc phdt triln rit nhanh nham tao ddpc cac cd quan tang phu cua ngddi tfl da, vdng mgc, van tim, xfldng, sun, bO ph$n hd hap, thin kinh... Cac san pham nay se la mdt li/c Iflpng kinh t l quan trpng dfla tren cdng nghe
TBG va dang dddc dau td manh me vi cd gid trj cao cho phapng phap y hoc tai tao cua t h i gidi trong the ky XXI.
V l ky thudt, cd nhflng mfle dp khac nhau tuy loai TBG va tang phij dfldc tdi tao. Cdng nghe tdi tao tgng phu thadng can phdi hpp cua nhieu vat lieu va ky thuat khac nhau, gdm khoa hpc vat lieu gia the, thilt ke md hinh, cdng nghe gen va te bao... Tren thdc te, nhflng san pham ddn thuan nha da, vdng mgc thudc ky thugt 2D, d l thanh cdng hdn va od kha nang flng dyng cao. Cdc san pham nay dflpc tao ra qua viec biet hoa TBG va cay md tren gid the hai chilu. Trong dieu kien nay, cac te bao tang trddng va tae dpng vdi nhau tao thanh san pham mdng nha da va vdng mac. Trong trfldng hpp nhd tim, than, rang, sfl phat triln va ket hpp cua te bao phflc tgp va te nhj hdn.
Ngoai gia the ba chilu (3D), cdn can nhflng yeu td cytokine chuyen biet de biet hoa va nhflng xuc tac hadng din te bao (ohemotaxin) di ddng tren gia t h i tao cau true 3D cho tgng phu. Gan day, cdng nghe in 3D da giup tao dflpc mdt sd cP quan nhfl gan va than. Mgt trd ngai Idn cho viec tao tang phu trong phdng thi nghiem la ngudn cung c i p mdu de cac tang phu od 6ii oxygen va cha't dinh dddng phat triln.
Vi gidi han ky thuat va ohi phf, cdng nghe 2D ddpc ooi la thfch hpp vdi nhu cau khai tnen TBG trong muc tieu tgo san pham sinh hpc d Viet Nam.
Tim kiem TBG mdi: ve bdn chat, quan the TBG trong chung ta chfnh la nhflng dapc lieu rat phong phu va da dang cd the dfldc vi nhd mdt rang ddpc thdo.
Nhflng ky thuat kiem dinh va danh gia cac ngudn TBG dd cd the giup chung ta khdm pha ra nhflng ddng TBG quy hiem vdi chdc nang trj lieu chuydn biet. Cac nha nghien cdu hien ludn nd lac tim kiem nhflng ddng TBG cd tinh an toan va hflu hieu hdn cac ddng hien tai. Tfl cuong rdn, ngoai "TBG mau", mgt sd ddng TBG mdi da dadc tim ra cd flng dung da nang nhfl "TBG cua mang cudng rdn" tri bdng bdi TS Phan Toan Thang (Dai hgc Singapore, 2005);
gan day mdt loai TBG cudng rdn toan nang dflpc kham pha cd the dfldc biet hoa thanh te bao tang cd kha nang trj benh tieu dddng (2012). Tfl tuy xUdng, mdt loai TBG mdi, da nang dddc gpi la "MultiStem"
(Athersis Inc.), cd kha nang nhan bdn vd hgn va khdng bj he miln djch dao thai. Mot kham phd khac tim ra "TBG rat nhd vdi dac tinh gidng TBG phdi"
(very small like ES cell) la mdt ddng TBG cd tilm nang tao nhieu loai te bao tr; lieu nhfl TBG phdi, Mdi ddng TBG mdi nay deu cd bdn quyen sd hflu tri tue vd dflpc cac nha kinh doanh lap hang, nghien cdu de mang lai nhflng ang dung thiet thyc. Tuy theo chac
Sfi 17 nam 2014 Tap cN KHOA HQC CONG NGHE VIET N^VfW
NGHIGN CDU-TRRO DOI
nang cac ddng TBG, trj gia cua hang cd the Id hang chyc hoac hang tram trieu USD.
Ket inan
Nhflng tien bd nhanh ehdng vd sinh hoat khoa hpc sdi ndi eua nghien cflu TBG tren the gidi hien nay dang tgo oho Viet Nam nhflng cd hpi phat trien cong nghd TBG vd ddng thdi cung dat ra nhflng thfl thach trong chpn Ifla mpt hadng di ed tinh khai pha, tieu chuan vd ben vflng. Vdi kien thfle vd ky thugt hien dai, chung ta ed the tham dfl vao ddng tien then cua the gidi qua nhflng hpp tac d l mang Igi nhflng flng dung quan trpng va thie't thdc cua TBG eho vide phyc vu y te Viet Nam. Tren binh dien vTmd, de phat trien thanh cong nhieu san pham kinh te va chat Iflpng cua cdng nghe TBG, sfl lien ket da nganh va hpp tac chat ehe gifla eae trung tam nghien cflu, ky nghe trong nfldo rat can dfldc ke hoach hoa va trien khai.
Nhin xa hdn, ngoai cd hdi v l dng dung va kmh te ma nhflng t i l n bd cua TBG mang lai, theo y kien cua Chung tdi, cP hpi v l nghien cflu sang tao oung rat can dflpc Iflu tam va co vu, dao biet la cho the he oac nha khoa hpc tre. Nhieu kham pha quan trpng oua the' gidi da hinh thanh tfl tfl duy sang tgo cua ea nhan.
V l cdng nghe sinh hpc, phflpng phap nhan ban gen da khai sinh ky nguyen Biotech do Herbert Boyer, UCSF, 1972; PCR cua Kary Mullis, 1983; TBG IPS cua Shinya Yamanaka, Kyoto, 2006. Nhflng ngfldi ndy da thanh edng tfl tu duy sang tao, chd khdng phai ta nhflng may mdc hien dai hay nhflng tai khoan nghien cflu Idn. Cd khi hp da lam viee trong dieu kien rat khd khan va di ngflpc dfl luan, nhang hp da ty lan md tim ra nhflng giai dap mang tinh cdch mang ky thuat cho t h i gidi. 6 nhieu phdng thi nghiem tren the gidi. nhflng k i t qua mdi dang dfldc thfle hien hang ngay tfl sfl sdng tao. Hien nay, d mdt sd nPi trong nadc, cac phdng thf nghiem khdng thie'u nhflng thiet bj hien dgi, nhflng chung ta thadng khdng dat va'n d l tfl duy sang tao mdt each dung mfle. Mong rang ngoai nhflng ke hoaeh dau tfl flng dung trj lieu va kinh doanh san xuat dfla tren cdng nghe TBG, chung ta se de cao va chu tam cho nghien cflu sang tao vdi mye tieu dat nhflng tien bd ddt pha eho cdng nghe TBG d VietNam ^
Tai ii^u tham lihao
with unlimited potential. Regenerative Medicine. May 2011, Vol. 6, No. 3, Pages 265-272.
2. http://www.researchandmarkets.com/research/3fkh92/steni_
celljherapy.
3. Okano H., Yamanaka S., iPS cell technologies: significance and applications to CNS regeneration and disease. Moi Brain. 2014 Mar31;7:22.
4 Riddell J1, Gazit R l , Garrison BSI, Quo G2, Saadatpour A3, Mandal PK1, Ebrna V^1, Volchkov PI, Yuan GC3, Orkin SH4, ROSSI DJ5. Reprogramming committedmunne blood cells to induced hematopoietic stem cells with defined factors.Cell. 2014 Apr24;157(3):549-64.
5. Mauroudi M., Zarogoulidis P., Porpodis K., Kioumis I., Lampaki S., Yarmus L., Malecki R., Zarogoulidis K., Malecki M., Stem cells' guided gene therapy ol cancer: New frontier in personalized and targeted therapy. J Cancer Res Ther (Manch). 2014;2(1}:22-33.
6. Hong Ma, Robert Moray. Ryan C. O'Neil, Yupeng He. Brittany Daughtry. Matthew 0, Schultz, Manoj Hariharan, Joseph R Nery, Rosa Castanon, Karen Sabatini, Rathi D Thiagarajan, Masahito Tachibana, Eunju Kang, Rebecca Tippner-Hedges, Riffat Ahmed.
Nuria Marti Gutierrez, Crystal Van Dyken, Alim Polat. Atsushi Sugawara, Michelle Sparman, Sumita Gokhale, Paula Amato, Don P.Vi/olf, Joseph R. Ecker, Louise C. Laurent et al Abnormalities in human pluripotent cells due to reprogramming mechanisms. Nature (2014)doi:10.1038/nature13551.
7 http.//www.isscr org/visitor-types/public/stem-cell-faq.
8. Chan T.M., Harn H J., Lin H.P., Chiu S.C, Lin P.C , Wang H.I., Ho L l „ Chuu CP., Chfou T W., Hsiefi A C, Chen Y.W., Ho W.Y, Lin S.Z , The Use of ADSCs as a Treatment for Chronic Stroke.
Cell Transplant. 2014;23(4):541-7.
9. Pham P.v., Vu N.B,, Pham V.M., Truong N.H., Pham T.L, Dang L.T„ Nguyen T.T., Bui A.N , Phan N.K , Good manufacturing practice-compliant isolation and culture of human umbilical cord blood-derived mesenchymal stem cells. J TransI Med. 2014 Feb 24,12:56.
10. Kurzweil R . Grossman T., Fantastic voyage: live long enough to live forever The science behind radical life extension questions and answers. Stud Health Technol Inform. 2009;149:187-94
11 Matsunari H 1., Nagashima H., Watanabe M., Umeyama K , Nakano K , Nagaya M., Kobayashi T.. Yamaguchi T., Sumazaki R., Herzenberg L.A., Nakauchi H , Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs.
ProcNatlAcadSciUSA. 2013Mar 19;110{12):4557-62.
12 Sekino Y., Sato K., Kanda Y,, Ishida S., Kokuritsu lyakuhin Shokuhin Eisei Kenkyusho Hokoku Developing and standardizing experimental protocols using human iPS-derived cells to predict adverse drug reactions in pre-clinical safety studies. Kokuritsu lyakuhin Shokuhin Eisei Kenkyusho Hokoku. (Japanese) 2013;(131):25-34.
13 http;//www.nature.com/news/stem-cells-taking-a-stand- against-pseudoscience-1.15408
14 http://www stemcellpioneers.com/showthread.php?8124- Neuralstem-to-use-Golorado-s-Right-to-Try-Law-to-Treat-ALS- patients.
1. Chris Mason, David A Bnndley, Emily J Culme-Seymour &
Natasha L Davie Cell therapy industry: billion dollar global business
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