Tam sim no Advances of Stem Cell-based Therapy Form Diseases

Abstract

Kab mob raumyog ib qho teeb meem kev noj qab haus huv thoob plaws ntiaj teb. Multidrug therapy siv nyob rau hauv niaj hnub kev kho mob raukab mob raumtsuas tuaj yeem ncua kev kis kab mob. Tsis muaj cov tshuaj no lossis kev kho mob tuaj yeem thim rov qab mus rau tus kab mob kawg. Yog li ntawd, tshawb nrhiav cov kev kho tshiab los txhim kho cov neeg mob lub neej zoo thiab tejzaum nws kho, rov qab, lossis txo cov kab mob raum yog qhov tseem ceeb. Stem cells muaj kev cog lus muaj peev xwm ua ib hom tshuaj kho dua tshiab raukab mob raumvim lawv qhov kev txwv tsis pub dhau thiab lawv lub peev xwm los sib txawv rau hauv lub raum hlwb hauv vitro. Mounting pov thawj los ntawm kev tswj hwm cov qia hlwb hauv kev sim kab mob raum qauv qhia tias qia cell-raws li kev kho mob muaj kev kho mob los yog kev tiv thaiv kab mob kom txo qis raum kev puas tsuaj thaum txhim kho kev ua haujlwm thiab cov qauv ntawm ob lub glomerular thiab tubular compartments. Qhov kev tshuaj xyuas no piav qhia txog cov kab mob ntawm cov kab mob tam sim no los ntawm kev kho mobkab mob raum,suav nrog ntau qhov chaw ntawm tes, tsiaj qauv, thiab kev tshawb fawb hauv vitro. Cov teeb meem ntawm kev nce qib los ntawm cov ntaub ntawv pov thawj-ntawm-txoj cai hauv chav kuaj mus rau kev siv tshuaj kho mob dav dav thiab cov txiaj ntsig ntawm tib neeg kev soj ntsuam tau tshaj tawm txog niaj hnub no kuj tseem ceeb. Kev vam meej ntawm kev kho mob ntawm tes tuaj yeem nthuav dav cov tshuaj kho dua tshiab yav tom ntej.

Cov lus tseem ceeb

Stem cells; Lub raum rov tsim dua tshiab; Kab mob raum; Mesenchymal qia hlwb; embryonic qia hlwb; Induced pluripotent qia hlwb

Core Tip

Stem cells muaj lub peev xwm los ua cov tshuaj kho dua tshiab los khokab mob raum. Muaj cov pov thawj txuas ntxiv qhia tias kev kho cov qia cell-based muaj cov teebmeem renoprotective kom txo qis raum kev puas tsuaj thaum txhim kho lub raum ua haujlwm. Qhov kev tshuaj xyuas no piav qhia txog cov kev kho mob ntawm cov stem cell raws li kev kho mob tam sim nokab mob raumnyob rau hauv cov qauv kev sim thiab cov txiaj ntsig los ntawm tib neeg kev sim tshuaj ntsuam xyuas tau tshaj tawm txog niaj hnub no.

Taw qhia 

Kab mob raum yog ib qho teeb meem kev noj qab haus huv thoob ntiaj teb. Ib qho kev ntsuam xyuas tshiab qhia tau hais tias kev nthuav dav thoob ntiaj tebmob raum mob (CKD)Hauv xyoo 2017, yog 9.1 feem pua ​​(697.5 lab tus neeg mob). Lub Koom Haum Saib Xyuas Kev Noj Qab Haus Huv Ntiaj Teb tau kwv yees tias ntau li 5 txog 10 lab tus tib neeg tuag txhua xyoo los ntawmkab mob raumthoob ntiaj teb. Los ntawm 2040, CKD tau kwv yees ua qhov thib tsib ua rau tuag thoob ntiaj teb.

Nyob rau hauv xyoo tas los no, kev tshawb fawb txog kev siv cov qia hlwb thiab cov tshuaj suav tshuaj ntsuab rau kev kho mob ntawmkab mob raumtau txais txiaj ntsig zoo. Lub ntsiab mechanism ntawm ob txoj kev kho mob yog los txhawb kev kho cov mob raum cov ntaub so ntswg thiab tiv thaiv lub raum tshuav nyiaj li cas.

Suav tshuaj ntsuab kho mob,cistanche, tau siv hauv tshuaj suav tshuaj los kho ntau yam mobkab mob raumtxij thaum ub los. Nws tau tshaj tawm tiascistanchemuaj peev xwm txo qhov mob,txo lub raum fibrosis, thiab txhawb cov synthesis ntawm extracellular matrix Cheebtsam. Nws tau raug tshaj tawm tias cov teebmeem no yog vim nws cov khoom siv bioactive, suav nrog ntau cov tshuaj phenolic, triterpenoids, thiab coumarins.

Nyem rau ntawm Cistanche Tubulosa Rau Raum Kab Mob

Yog xav paub ntxiv: david.deng@wecistanche.com

Ntawm qhov tod tes, stem cell technology tau ua rau muaj kev hloov pauv hauv kev kho mob. Kev tshawb fawb tau pom tias cov qia hlwb tuaj yeem sib txawv rau ntau hom ntawm lub raum hlwb thiab ua cov haujlwm kho mob, suav nrog kev tiv thaiv cov ntaub so ntswg raum, ua kom cov nqaij mos fibrosis, thiab kho cov ntaub so ntswg puas.

Thaum kawg, kev sib xyaw ntawm cov tshuaj suav tshuaj suav nrog kev tshawb fawb niaj hnub tuaj yeem yog tus yuam sij rau kev kho ntau yamkab mob raum. Cov tswv yim no tau maj mam lees txais los ntawm cov neeg kho mob thiab cov kev tshawb fawb tau pom tias kev kho mob ua ke ntawm cistanche thiab qia cell kho yuav txo tau qhov kev tuag ntawm cov neeg tuag.kab mob raum. 

Hauv kev xaus, kev siv cistanche thiab qia cell kho hauv kev kho mob ntawmkab mob raumqhia tau hais tias muaj peev xwm zoo thiab xav tau kev tshawb fawb ntxiv. Kev sib xyaw ua ke ntawm ob txoj kev kho mob tuaj yeem muab kev kho mob zoo dua rau cov neeg uas tab tom ntsibkab mob raum.

Txog rau tam sim no, tsis muaj kev cuam tshuam tseem ceeb hauv kev kho mob ntawmkab mob raum,hos txoj kev kho niaj hnub niaj hnub no suav nrog kev kho ntau yam tshuaj tsuas tuaj yeem ncua tus kab mob mus ntxiv. Cov tshuaj no tsis tuaj yeem thim rov qab mus rau qhov mob raum kawg (ESKD). Kev kho tam sim no repertoire kom ntev lub neej ntawm ESKD cov neeg mob yog txwv rau kev hloov lub raum

kev kho mob, kev lim ntshav, lossis hloov lub cev. Vim tias tus nqi kho mob siab koom nrog hauv kev kho mob lim ntshav, uas tseem cuam tshuam rau tus neeg mob lub neej zoo, kev lim ntshav tsis yog qhov zoo tshaj plaws. Qhov no feem ntau yog vim kev lim ntshav tsis kho lossis hloov txhua lub raum ua haujlwm. Lub caij no, qhov tsis txaus siab ntawm cov neeg pub khoom nruab nrog cev thiab qhov muaj peev xwm tsis lees paub lub cev muaj peev xwm txwv txoj kev hloov pauv raum. Yog li ntawd, nws yog ib qho tseem ceeb uas cov kws tshawb fawb kho mob tshawb nrhiav cov kev kho tshiab los txhim kho lub neej zoo rau cov neeg mobkab mob raumthiab muaj peev xwm kho tau, thim rov qab, lossis txo cov kab mob raum.

Stem cells txhais tau tias yog cov hlwb muaj peev xwm rov ua dua nws tus kheej thiab tuaj yeem sib txawv rau ntau hom cell. Tsis tas li ntawd, qia hlwb muaj cellular plasticity thiab yooj yim nthuav hauv vitro, uas yog cov txiaj ntsig zoo ntawm cov qia cell kho. Stem cells tau tshawb nrhiav ntau hauv kev kho mob plawv, neuron, vascular, immunological, thiabkab mob raum. Hauv qee lub tebchaws, muaj cov kab mob qog noj ntshav raws li mesenchymal qia hlwb (MSCs), uas muaj raws li cov khoom lag luam pom zoo los ntawm cov koom haum tswj hwm hauv zos rau cov kab mob tshwj xeeb lossis kev qhia txog kev noj qab haus huv. Yog li, daim ntawv no ntawm kev cuam tshuam tuaj yeem ua rau txoj hauv kev rau cov tshuaj rov ua dua tshiab rau tib neeg cov kab mob. Daim duab 1 tau qhia txog cov ntsiab lus ntawm qia cell-based cov tswv yim los khokab mob raum.

Cov kab lus tam sim no tshuaj xyuas cov qia cell-raws li kev kho mob hauv lub raum rov ua dua tshiab raws li tsiaj cov qauv thiab kev tshawb fawb hauv vitro, nrog rau kev sib tham txog nws lub peev xwm rau kev siv tshuaj kho mob thiab cov teeb meem hauv kev txhais los ntawm cov qauv tsiaj rau kev kho mob.

EMBRYONIC STEM CELLS

Embryonic qia hlwb (ESCs) yog pluripotent hlwb nrog unlimited sib txawv muaj peev xwm. Ntau pab pawg tshawb fawb tau pom tias nas ESCs tuaj yeem koom ua ke rau hauv lub raum, qhia txog qhov muaj peev xwm ntawm cov qia hlwb hauv kev kho raum. Kev cog qoob loo ntawm ESCs ncaj qha rau hauv nas embryonic raum kab lis kev cai ua rau ESC-derived tubules thiab proximal tubular cells. Kev nthuav tawm ESCs rau cov inducers tshwj xeeb lossis yam tseem ceeb kuj ua rau induction ntawm cov hlwb kom sib txawv rau hauv lub raum kab mob hauv vitro. Kim thiab Dressler induced nas ESCs kom sib txawv rau hauv lub raum progenitor hlwb thiab ces muab cov hlwb mus rau hauv tubular epithelial los ntawm txhaj rau hauv embryonic raum kab lis kev cai. Hauv lwm txoj kev tshawb fawb, thaum lub raum tsis zoo ntawm lub raum tau decellularised hauv qhov no, lub raum cov txheej txheem sib txawv tau khaws cia, thiab cov noob ESCs tuaj yeem nthuav dav hauv glomerular, vascular, thiab tubular qauv. Vazquez-Zapien et al tau tshaj tawm ntxiv tias tom qab nas nrog cisplatin-vim lub raum tsis ua haujlwm tau txais nas ESCs los ntawm kev txhaj tshuaj, cov neeg tuag tau txo qis thiab tiv thaiv cov kab mob ntsig txog kev puas tsuaj ntxiv.

Daim duab 1 Txheej txheem cej luam ntawm stem cell-based tswv yim los kho mob raum.Ntau hom qia hlwb tau tshawb nrhiav rau lawv lub peev xwm los kho kab mob raum. Ib lub tswv yim yog los coj kev sib txawv ntawm cov qia hlwb mus rau hauv lub raum tiv thaiv cov hlwb hauv vitro lossis hauv vivo los hloov cov hlwb raug mob lossis puas. Lwm cov tswv yim yog los hloov cov qia hlwb los yog qia cell-derived extracellular vesicles los tsim cov nyhuv paracrine / endocrine nyhuv thiab siv lub raum organoid tsim los hloov tag nrho lub raum kab mob.

Lub raum, ntawm qhov tod tes, yog ib lub cev muaj zog heev uas ua los ntawm ntau hom cell (Daim duab 2). Yog li ntawd, nws yog ib qho nyuaj rau reconstruct. Ntau tus kws tshawb fawb tau ua haujlwm ntawm cov txheej txheem los txhawb ESCs rau hauv kev tsim cov qauv tsim kom zoo li lub raum nrog ntau lub raum ntawm tes thiab muaj peev xwm ntawm tus kheej lub koom haum, hu ua organoid. Tan li al qhia tias nas ESCs-derived nephron progenitors, aggregated nrog thawj ureteric bud, tsim raum organoids nrog tag nrho cov nephron lug.

Txawm hais tias nws lub peev xwm kho mob, qhov kev pheej hmoo ntawm qog nqaij hlav, nrog rau kev txhawj xeeb txog kev cai lij choj thiab kev coj ncaj ncees, txuas ntxiv mus cuam tshuam kev txhim kho ntawm SC-raws li kev kho mob. Tsis tas li ntawd, ESC-derived hlwb sib txawv yog allogeneic nyob rau hauv cov xwm thiab muaj peev xwm yog li ntawd qhia tshwj xeeb nto proteins los ua rau tus neeg tau txais kev tiv thaiv kab mob. Yog li ntawd, kev tsis lees paub mob hnyav thiab mob ntev, lossis kab mob graft vs tus tswv tsev, tuaj yeem tshwm sim vim kev siv cov allografts yog tias lawv tsis ua tiav kev tiv thaiv kab mob nrog tus neeg tau txais kev pab.

INDUCED PLURIPOTENT STEM CELLS

Induced pluripotent stem cells (iPSCs) qhia ntau yam khoom siv nrog ESCs. Hauv xyoo 2006, Takahashi thiab Yamanaka tau qhia tias nas cov neeg laus fibroblasts tuaj yeem rov ua dua rau hauv iPSCs, los ntawm kev qhia plaub yam kev hloov pauv (OCT4, SOX2, KLF4, thiab c-MYC). Qhov no yog ib qho kev tshawb nrhiav uas tau dhau los ua qhov tseem ceeb hauv kev tshawb fawb qia cell. Kev txhim kho ntawm iPSCs-raws li kev kho mob tuaj yeem kov yeej cov teeb meem tshwj xeeb ntsig txog kev siv ESCs, xws li kev txhawj xeeb txog kev coj ncaj ncees vim yog lub hlwb thiab lub peev xwm ntawm kev tsis lees paub ntawm tes los ntawm tus neeg mob.

Kev siv ESCs muaj nws qhov kev tsis sib haum xeeb vim qee cov tog neeg uas xav tias kev rhuav tshem lub embryo rau nws cov ESCs zoo li tua tus menyuam hauv plab. Li no, iPSCs yog ib qho kev ntxim nyiam rau ESC-zoo li qia hlwb raws li iPSCs tuaj yeem tsim los ntawm cov neeg laus. Cov hlwb no tseem khaws cov keeb kwm ntawm caj ces thiab peculiar epigenetic nco ntawm lawv niam txiv cell, yog li muaj peev xwm zam tsis muaj zog tiv thaiv kab mob. Txog niaj hnub no, iPSCs tau tsim los ntawm fibroblasts, umbilical cord blood, peripheral blood, thiab keratinocytes. Cov kws tshawb fawb tseem tau ua tiav cov iPSCs los ntawm cov hlwb mesangial, lub raum tubular hlwb, thiab lub raum epithelial hlwb. Reprogrammed iPSCs los ntawm lub raum hlwb ntseeg tau tias muaj peev xwm pab tau hauv kev tshawb nrhiav caj ceskab mob raum,uas yuav ua rau kev txhim kho cov kev kho tshiab.

Lub peev xwm ntawm iPSCs hauv lub raum rov tsim dua tshiab tau tshawb nrhiav, suav nrog tsim cov txheej txheem tshwj xeeb los txhawb tib neeg iPSCs kom sib txawv rau hauv cov kab mob hauv lub raum lossis cov qauv peb sab ntawm lub raum. Toyohara thiab al tau tsim ib qho kev sib txawv ntawm ntau qhov kev cai los ntxias tib neeg iPSCs kom sib txawv rau hauv lub raum progenitors muaj peev xwm tsim peb-dimensional proximal raum tubule zoo li cov qauv hauv vitro. Tib pab pawg tom qab pom tias kev hloov pauv hauv lub raum subcapsular ntawm cov tib neeg iPSC-los ntawm lub raum progenitors ameliorated mob raum raug mob (AKI) hauv tus qauv tsiaj.

Ntxiv nrog rau kev cia siab rau qhov sib txawv muaj peev xwm ntawm iPSCs, cov kws tshawb fawb kuj tau siv cov khoom siv renotropic tsim los ntawm iPSCs hauv lub raum rov tsim dua tshiab. Kev hloov pauv ntawm iPSCs hauv cov qauv murine nrog ischemic AKI, txo qhov kev qhia ntawm cov tshuaj oxidative, pro-inflammatory cytokines, thiab apoptotic yam, uas ua rau muaj kev txhim kho hauv kev ciaj sia. Tsis tas li ntawd, Tarng et al tau qhia tias iPSCs-muab cov txheej txheem nruab nrab tau txo qis AKI thiab txhim kho txoj sia nyob hauv tus qauv tsiaj.

Los ntawm kev txhim kho tsis ntev los no, iPSCs tam sim no tuaj yeem raug coj mus rau qhov sib txawv thiab tsim kom muaj lub raum organoids zoo li tib neeg lub raum hauv vitro. Tib neeg lub raum tsim tau tuaj yeem siv rau hauv cov tshuaj kho dua tshiab, thiab hauv kev loj hlob, toxicity, thiab kab mob qauv. Tsis tas li ntawd, siv cov neeg mob tus kheej iPSCs los tsim kom muaj lub raum zoo organoids ua rau kev siv tshuaj siv tau raws li tus neeg mob tshwj xeeb. Qhov no yog pab txhawb los ntawm kev sib raug nruj ntawm tus neeg mob tus neeg mob keeb kwm yav dhau los thiab kev siv tshuaj. Melissa H Little cov pab pawg tau ua tiav tsim tib neeg iPSCs-muab raum organoids uas muaj tag nrho cov kev cia siab rau lub raum cell. Cov organoids muaj nephrons segmented rau hauv lub glomerulus, proximal tubule, ib lub voj ntawm Henle, thiab distal tubule nrog rau cov ducts, endothelial network, thiab lub raum interstitium. Lub caij no, zoo sib xws, IzpisuaBelmonte pawg kuj tau tsim ib lub raum organoid uas muaj glomeruli nrog podocytes, proximal thiab distal tubule hlwb, thiab endothelial hlwb. Morizane thiab tau tshaj tawm ntau qhov kev sib txawv ntawm cov txheej txheem tsim rau lub raum organoids nrog epithelial nephron zoo li cov qauv. Cov organoids no qhia cov cim rau podocytes, proximal tubules, loops ntawm Henle, thiab distal tubules.

Lwm pab pawg tshawb fawb tau tshaj tawm tias iPSCs muab los ntawm ntau hom xovtooj ntawm tes tsis zoo ib yam hauv lawv lub peev xwm sib txawv. Qhov no yuav tshwm sim vim tias iPSCs tuav lub cim xeeb epigenetic ntawm lawv niam txiv lub hlwb. Yog li ntawd, lub raum parenchymal hlwb yuav yog ib tus neeg sib tw zoo dua li cov hlwb los ntawm lwm cov ntaub so ntswg rau reprogramming los khokab mob raum.

ENDOTHELIAL PROGENITOR CELLS

Endothelial progenitor cells (EPCs) muaj lub luag haujlwm tseem ceeb hauv kev tswj hwm vascular kev ncaj ncees thiab kho txhua hom kev puas tsuaj endothelial. EPCs tuaj yeem raug cais tawm los ntawm ntau lub xov tooj ntawm tes, feem ntau yog los ntawm cov pob txha pob txha, cov ntshav qaum, thiab cov ntshav peripheral. Cov txiaj ntsig zoo ntawm EPCs-raws li kev kho mob tau pom nyob rau hauv cov kev tshawb fawb tau ua los ntawm cov qauv sib txawv ntawmkab mob raumxws li AKI,CKD, thiab lub raum hlab ntsha stenosis. Nyob rau hauv cov tsiaj qauv ntawm lub raum ischemia / reperfusion (I / R)-induced AKI, lub raum hlab ntsha-derived EPC-zoo li cov hlwb koom ua ke rau hauv endothelium tom qab AKI, ua rau txo qis ntawm cov ntshav creatinine (SCr) thiab albuminuria thaum cov ntshav khiav tau zoo. Patschan thiab al ntxiv qhia tau hais tias qhov kev txhaj tshuaj ntawm cov ntshav peripheral tau txais los ntawm EPCs thaum ntxov tau txo qis SCr, ameliorated interstitial fibrosis, thiab tom qab ntawd txo qhov kev loj hlob mus rauCKDqab AKI.

Cov txiaj ntsig ntawm EPC kev kho mob ntawm CKD tau kawm hauv tus qauv tsiaj. Nyob rau hauv txoj kev tshawb no, cov pob txha pob txha-derived EPCs uas tau nyob rau hauv lub raum raug mob tiv thaiv tus mob inflammatory los ntawm adversely cuam tshuam rau lub raum, thiab ua tau zoo khaws cia rau lub raum kev ua haujlwm thiab cov qauv. Huang et al tau qhia tus qauv nas uas tau txhaj nrog cov ntshav peripheral los ntawm EPCs thiab pom zoo inhibition ntawm kev nthuav tawm ntawm CKD thiab ua rau lub raum ua haujlwm tsis zoo. Cov hlwb txhaj tshuaj txhim kho angiogenesis thiab ntshav khiav thiab muaj peev xwm tiv thaiv oxidative thaum suppressing o, oxidative kev nyuaj siab, apoptosis, thiab fibrosis. Meanwhile, nyob rau hauv lub raum hlab ntsha stenosis qauv, peripheral ntshav derived EPCs qhia renoprotective teebmeem tom qab txhaj rau hauv lub raum stenotic, los ntawm kev txhim kho microvascular ntom thiab lub raum ua hauj lwm nrog rau kev txo qis fibrosis.

MSCs

MSCs, los yog tsis ntev los no hu ua mesenchymal stromal hlwb, tau pom thawj zaug los ntawm Friedenstein thiab nws cov npoj yaig los ntawm cov pob txha pob txha. Tau ntau xyoo, cov kws tshawb fawb tau pom tias MSCs tuaj yeem raug cais tawm ntawm ntau yam kabmob lossis cov ntaub so ntswg, xws li cov ntaub so ntswg adipose, umbilical cord, placenta, peripheral blood, amniotic fluid, thiab pob txha pob txha.

Cov pob txha pob txha yog qhov feem ntau siv rau MSCs hauv kev kho mob, suav nrog kev kho mobkab mob raum.Txawm li cas los xij, kev siv cov pob txha pob txha derived-MSCs (BM-MSCs) tau raug txwv vim tias muaj cov kab mob kis tau zoo, thiab lub peev xwm ntawm cov cell proliferation/differentiation txo qis thaum tus neeg pub lub hnub nyoog nce. Yog li, cov kws tshawb fawb tau pib tshawb nrhiav lwm hom MSCs rau lub raum rov tsim dua tshiab. Ntawm ntau qhov chaw, adipose cov ntaub so ntswg-derived MSCs (AD-MSCs) thiab umbilical cord-derived MSCs (UC-MSCs) tau dhau los ua cov neeg sib tw uas xav tau vim tias muaj ntau ntawm MSCs tuaj yeem tau txais los ntawm kev siv cov txheej txheem cuam tshuam tsawg heev.

Hauv thaj tsam ntawm kab mob raum, MSCs yog ib qho ntawm cov neeg muaj txiaj ntsig zoo tshaj plaws rau kev ua kom rov tsim dua tshiab hauv lub raum puas. Cov ntawv ceeb toom ua ntej tau ua pov thawj pom tias muaj peev xwm kho tau ntawm MSCs hauv cov qauv tsiaj ntawm AKI thiabCKD.Raws li kev tshuaj xyuas ntau dua 70 kab lus, MSCs yog ib qho ntawm cov neeg muaj txiaj ntsig zoo tshaj plaws los kho kev sim.CKD.Lub caij no, nyob rau hauv ib qho kev tshuaj ntsuam xyuas nrog rau tsiaj cov qauv ntawm cov mob ntev thiab AKI, MSCs tau coj mus rau lub raum rov tsim dua tshiab txawm tias muaj kev hloov pauv ntawm kev tswj hwm (arterial, venous, lossis lub raum). Muaj cov pov thawj qhia txog cov txiaj ntsig zoo ntawm MSCs hauv kev thaiv kev hloov pauv AKI-CKD, ib lo lus siv los piav qhia txog kev rov ua tsis tiav los ntawm AKI uas ua rau muaj kev ua haujlwm tsis zoo rau lub sijhawm ntev, xws liCKD.

Hauv kev sim ua los ntawm Brasile li al, thaum tshuaj lom neeg lub raum puas tau perfused ex vivo nrog MSCs rau 24 teev, lub raum rov tsim dua tshiab tau sau tseg. MSCs-raws li kev kho mob ua rau lub raum los ua ke txo qis ntawm cov kab mob cytokines. Piv rau exsanguinous metabolic kev txhawb nqa perfusion ib leeg, muaj qhov nce ntxiv ntawm cov hlwb hauv lub raum uas raug mitosis hauv MSCs-kho raum.

Ntau cov kev tshawb fawb tau pom tias MSCs tuaj yeem sib txawv rau hauv lub raum hlwb feem ntau lossis tshwj xeeb rau hauv lub raum cov hlwb xws li lub raum epithelial cells, mesangial cells, thiab endothelial cells.

BM-MSCs

Ntau cov kev tshawb fawb tau pom qhov ua tau zoo ntawm BM-MSCs hauv kev kho mob raum siv tsiaj cov qauv ntawm AKI, podocyte raug mob, thiab glomerulonephropathy. Morigi et al yog cov thawj pab pawg los qhia txog lub luag haujlwm ntawm kev tiv thaiv kev tiv thaiv ntawm BM-MSCs thiab tau sau tseg cov peev txheej kho mob ntawm tib neeg BM-MSCs hauv kev kho mob.kab mob raum,ua rau muaj sia nyob hauv cov qauv tsiaj. Kev hloov pauv ntawm tib neeg BM-MSCs rau hauv cisplatin-induced AKI nas ua rau lub raum ua haujlwm tau zoo thiab rov zoo los ntawm kev ua kom cov tubular proliferation thiab txo cov tubules cuam tshuam los ntawm apoptosis, necrosis, thiab tubular lesions. Ib daim ntawv tiv thaiv zoo sib xws tau muab los ntawm kev txhaj tshuaj BM-MSCs hauv glycerol-induced pigment nephropathy qauv thiab I / R-induced AKI. Qhov tseem ceeb tshaj, infused BM-MSCs tau pom tias yuav txhim kho lub raum kev ua haujlwm rov qab txawm tias siv 24 teev tom qab raug mob. Tsis tas li ntawd, BM-MSCs tau zoo dua hauv kev kho AKI hauv cov qauv tsiaj piv rau candesartan, uas yog angiotensin II blocker. Hauv qhov tseem ceeb, muaj pov thawj zoo tias thaum MSCs tau hloov pauv hauv cov qauv tsiaj muaj tshuaj lom thiab ischemic, cov hlwb tiv thaiv cov tsiaj tiv thaiv AKI thiab ua kom lub sijhawm rov zoo.

BM-MSCs kuj tau pom cov lus cog tseg hauv kev kho mobCKDhauv cov qauv tsiaj. BM-MSCs tiv thaiv kev poob ntawm peritubular capillaries thiab ua rau qeeb qeeb ntawm cov proteinuria (cov protein nyob hauv cov zis). Thaum lub sij hawm thawj theem ntawm kev tiv thaiv kab mob ua ntej pib ntawmCKD,cov hlwb no kuj txo lub raum fibrosis. Raws li histological tsom xam ntawm tus nas qauv nrogCKD, BM-MSCs txo glomerulosclerosis, uas ua rau kev khaws cia ntawm lub raum ua haujlwm thiab txo qis ntawm lub raum raug mob. Tsis tas li ntawd, thaum cov tsiaj ua qauv nrog CKD tau kho nrog BM-MSCs, muaj kev txo qis ntawm cov proteinuria thiab tsis tshua muaj engraftment ntawm cov hlwb hauv lub raum. Cov kev soj ntsuam no tau qhia tias cov txiaj ntsig zoo no yog tshwm sim los ntawm cytokines lossis kev loj hlob, uas tseem hu ua paracrine secretion ntawm cov neeg kho kom haum xeeb.

Ntxiv rau qhov muaj peev xwm ntawm BM-MSCs kom sib txawv rau hauv lub raum hlwb, cov ntaub ntawv tsis ntev los no tau qhia tias BM-MSCs tiv thaiv thiab rov tsim cov teebmeem ntawm ob lub raum los ntawm lawv cov paracrine anti-inflammatory, anti-fibrotic, thiab vascularisation zog. Raws li cov lus ceeb toom, BM-MSCs tuaj yeem hloov pauv cov kab mob lom neeg los ntawm kev tso tawm ntawm cov hlwv extracellular (EVs) los txhawb cov txheej txheem regenerative hauv cov hlwb raug mob.

Ntau qhov kev tshawb fawb tau tshawb xyuas qhov cuam tshuam ntawm BM-MSCs hauv kev sim ua qauv ntawm kev hloov pauv hauv lub raum. Feem ntau cov kev tshawb fawb tsom mus rau kev cuam tshuam qhov ua tau zoo los ntawm kev ua kom muaj sia nyob ntev ntev thiab inhibition ntawm cov txheej txheem tsis lees paub. Muab qhov zoo ntawm BM-MSCs uas muaj cov tshuaj tiv thaiv kab mob tsis zoo thiab cov tshuaj tiv thaiv kab mob, BM-MSCs tuaj yeem txo cov kev raug mob ntawm alloimmune thiab tiv thaiv kev tiv thaiv kev tiv thaiv kab mob los ua kom zoo rau kev khaws cia ntawm lub raum kev ua haujlwm.

AD-MSCs

AD-MSCs muaj ntau heev hauv cov ntaub so ntswg adipose thiab tuaj yeem yooj yim tshem tawm ntawm liposuction, ib txoj kev uas tau siv dav hauv qhov chaw kho mob. Cov ntaub so ntswg adipose tuaj yeem dhau los ua qhov nyiam ntawm MSCs vim nws qhov kev cuam tshuam tsawg dua thiab MSCs siab dua li cov uas pom hauv cov pob txha. Lawv qhov kev hloov pauv tsis haum ntawm txoj hauv kev hauv lub raum tau ua rau muaj qhov qis ntawm necrosis tab sis ua rau muaj vascularisation ntau dua ntawm lub raum parenchyma hauv Wister nas. Muaj cov lus ceeb toom txog kev kho mob ntawm AD-MSCs hauv AKI-induced tsiaj qauv. Kim et al tau ua pov thawj tias AD-MSCs txo qis apoptotic cell tuag thaum ib txhij txo qhov ua kom p53, c-Jun NH2-terminal kinase, thiab extracellular signal-regulated kinase, uas yog cov kab mob ntsig txog cov kab mob. Cov teebmeem no ua rau muaj kev muaj sia nyob ntau ntxiv ntawm AKI-induced tsiaj. Katsuno et al tau tshawb pom ntxiv tias tib neeg AD-MSCs kab lis kev cai hauv cov ntshav qis tau zais cov qib siab ntawm hepatocyte thiab vascular endothelial kev loj hlob yam. Thaum cov hlwb no tau hloov mus rau hauv AKI-induced nas, lawv txhim kho qhov txo qis ntawm lub raum puas. Txawm hais tias cov ntaub so ntswg adipose yog qhov zoo ntawm MSCs, AD-MSCs tau ua haujlwm tsawg dua hauv kev loj hlob thiab lub raum rov ua haujlwm piv rau BM-MSCs.

UAS-MSCs

Kev sau yooj yim ntawm UC-MSCs muab qhov chaw tshiab ntawm MSCs. Kev siv UC-MSCs hloov pauv cov pov tseg kev kho mob mus rau hauv cov khoom muaj txiaj ntsig nrog kev siv tshuaj kho mob. Piv rau MSCs los ntawm lwm qhov chaw, UC-MSCs muaj kev tiv thaiv kab mob tsawg, yog li tiv thaiv qhov tshwm sim ntawm kev tiv thaiv kab mob hauv kev hloov pauv ntawm allogeneic. Ntxiv mus, UC-MSCs muaj peev xwm nthuav dav dua piv rau BM-MSCs thiab AD-MSCs. UC-MSCs kuj tseem tsis pom muaj qhov tshwm sim ntawm qhov tshwm sim ntau dhau, yog li kev tsim cov cell loj ntawm UC-MSCs yog qhov ua tau zoo yam tsis ua rau poob ntawm lub zog ntawm tes.

Lwm qhov chaw ntawm MSCs

Ntxiv rau BM-MSCs, AD-MSCs, thiab UC-MSCs, cov kws tshawb fawb kuj tau siv lwm hom MSCs uas tsis tshua muaj kev kawm rau cov kev tshawb fawb rau lub raum. Kev ua tau zoo ntawm cov hlab ntshav-derived MSCs (CB-MSCs) kev tswj hwm hauv kev rov ua haujlwm ntawm lub raum tau raug tshaj tawm hauv cov qauv AKI tsiaj. Txoj kev tshawb no pom tau hais tias CB-MSCs txhawb lub raum rov tsim dua tshiab thiab ua rau lub neej muaj sia nyob ntev. Raws li txoj kev tshawb no, paracrine kev txiav txim ntawm CB-MSCs ntawm cov tubular hlwb yuav tau kho los ntawm kev txo qis ntawm oxidative kev nyuaj siab, apoptosis, thiab o. Hauser et al thiab George li al pom tias amniotic kua-derived MSCs (AF-MSCs) muaj cov yam ntxwv zoo ib yam li BM-MCSs, pab txhawb kev ua haujlwm thiab kev txhim kho hauv cov qauv nas.CKD.Sedrakyan et al tau qhia txog kev txhaj tshuaj ntawm AF-MSCs hauv cov nas ncua kev loj hlob ntawm lub raum fibrosis. Meanwhile, hauv aCKD-induced nas qauv nyob rau hauv kev tshawb fawb los ntawm Cetinkaya li al, transplanted placenta-derived MSCs (PL-MSCs) alleviated raum puas thiab inhibited fibrosis-induced apoptosis. PL-MSCs kuj tau siv los kho lub raum raug mob thiab o hauv cov nas mob lupus nephritis (LN).

STEM CELL-DERIVED EVs

EVs yog cov me me membrane vesicles secreted los ntawm ntau lub hlwb thiab pom nyob rau hauv feem ntau lub cev kua. Qhov kev tshuaj xyuas no siv lo lus dav dav, EVs, vim tias tsis muaj txoj hauv kev los txheeb xyuas cov vesicles. EVs tuaj yeem muab faib ua peb pawg loj, uas yog exosomes, microvesicles, thiab apoptotic lub cev. Hauv cov ntsiab lus tam sim no, cov kws tshawb fawb pom tias EVs tuaj yeem hloov mus rau cov hlwb raug mob los tswj cov ntaub so ntswg raug mob, txo qhov mob, inhibit apoptosis, thiab ua rau lub voj voog ntawm cov cell rov nkag mus rau hauv cov hlwb, tag nrho cov uas ua rau cell proliferation, cov ntaub so ntswg kho tus kheej, thiab rov tsim dua tshiab. Raws li kev tswj hwm nrog cov txheej txheem kho mob, EVs yuav ua raws li cov kab mob qia hlwb hauv ntau yam kev sim ua qauv.

Kev siv cov qia cell-derived EVs tuaj yeem muaj ntau yam zoo hauv daim ntawv thov kev kho mob suav nrog kev hla feem ntau ntawm kev txhawj xeeb txog kev nyab xeeb cuam tshuam txog kev kho cov qia cell, xws li kev sib kis ntawm cov cellular nrog oncogenic hlwb, qog nqaij hlav, thiab emboli tsim tom qab hloov pauv. Ib yam li ntawd, EVs kuj tseem ua rau muaj ntau yam kev siv peev xwm rau cov cab kuj molecules rau kev txhim kho hauv kev xa khoom thiab cov kev xav tau. EVs kuj tseem tuaj yeem khaws cia hauv cov chaw kho mob yam tsis tau poob lawv txoj haujlwm.

Ntau qhov kev tshawb fawb tau muab pov thawj ntseeg tau tias muaj peev xwm rov tsim dua tshiab ntawm EVs tso tawm los ntawm cov qia hlwb, tshwj xeeb yog MSCs, hauv cov qauv sib txawv ntawm lub raum raug mob. Cov kev tshawb fawb hauv vitro tau pom tias muaj peev xwm ntawm MSCs-derived EVs hloov mRNA, miRNA, thiab cov proteins rau lub raum hlwb. Tam sim no, qhov kev kho mob tsis pub dawb no tau kawm hauv cov qauv tsiaj ntawm AKI thiab CKD. Intravenous MSC-derived EVs siv cov teebmeem renoprotective los ntawm kev txo lub raum cell puas thiab apoptosis thaum pab txhawb kev loj hlob ntawm lub raum hlwb. Cov teebmeem no ua rau lub raum ua haujlwm tau zoo, zoo ib yam li cov uas raug ntxias los ntawm MSCs, raws li tau tshaj tawm hauv cov nas uas tau txhaj nrog EVs los ntawm EPCs thiab iPSCs.

Thaum tus neeg mob nyob nrog ESKD tau hloov lub raum, tus neeg mob lub neej zoo dua qub. Txawm li cas los xij, tus mob allograft nephropathy txwv tsis pub muaj sia nyob, ua rau tus neeg mob yuav tsum tau hloov lub raum ntau dua ib zaug hauv lub neej. Kev tswj hwm ntawm EVs tom qab hloov lub raum tau pom tias txhawm rau txhim kho I / R raug mob nyob rau hauv ob qho tib si mob thiab mob ntev, txaus siab rau kev ua siab ntev thiab ua kom muaj sia nyob ntev.

Lub preconditioning ntawm lub raum nrog qia hlwb-derived EVs kuj tseem yuav yooj yim txwv cov ntaub so ntswg puas los ntawm kev mob allograft nephropathy. Cov ntaub ntawv pov thawj pom tias MSCs-los ntawm EVs xa hauv perfusate thaum lub cev txias perfusion rau 4 h tiv thaiv lub raum los ntawm kev puas tsuaj rov qab thiab tuaj yeem khaws lub cev lub cev lub tshuab enzymatic, uas yog qhov tseem ceeb rau cell viability.

TXOJ CAI LOS NTAWM ANIMAL MODEL RAU HUMAN CLINICAL APPLICATION: LUB SIJ HAWM

Txawm hais tias muaj ntau yam kev sim tsiaj los ua kom pom qhov ua tau zoo ntawm cov qia cell kho hauv cov kab mob hauv lub raum, cov txiaj ntsig ntawm cov qauv tsiaj no tau ua tsis tiav hauv tib neeg kev tshawb fawb soj ntsuam tag nrho. Qhov tsis ua tiav los txhais cov txiaj ntsig tau zoo los ntawm kev sim tsiaj, uas muaj lub suab thiab tus qauv tsim thiab kev coj ua, rau kev siv tshuaj kho mob tshwm sim vim muaj kev hloov pauv ntawm tus qauv tsiaj thiab tib neeg lub cev.

Tib neegkab mob raumfeem ntau yog tsim los ntawm tus tsiaj qauv. Kev raug mob vim yog feem ntau mob, thiab tsis muaj lub cev, thiab tsis tuaj yeem ua rau tib neegkab mob raum' complex pathological nta. Nws yog li nyuaj rau precisely simulate los yog kwv yees cov lus teb ntawm tib neeg lub raum kab mob rau kev kho mob los ntawm kev siv tus tsiaj qauv. CKD kev sim tsiaj tsis txaus los cuam tshuam txog tus kab mob no vim tias lwm yam xws li hnub nyoog, poj niam txiv neej, thiab comorbidities tsis sawv cev. Cov neeg mob CKD kuj tseem tuaj yeem muaj comorbidities uas muaj ntau yam kabmob thiab kev ua haujlwm uas ua rau cov txheej txheem pathological hauv qab CKD. Hauv cov qauv tsiaj, txawm li cas los xij, cov teeb meem no tsis tau muab coj los rau hauv tus account.

Ob leeg tib neeg thiab tsiaj tej zaum yuav muaj tib yam protein ua haujlwm tab sis muaj cov hom tshwj xeeb sib txawv hauv cov kev cai molecular ntawm cov noob. Qhov no ua rau muaj teeb meem hauv kev nthuav tawm qhov tshwm sim los ntawm kev txheeb xyuas cov noob tsiaj rau cov mob ntawm lub cev hauv tib neeg lub cev. Qhov sib txawv ntawm cov tsiaj 'thiab tib neeg' lub cev tiv thaiv kab mob yog lwm qhov laj thawj rau kev tsis ua haujlwm los txhais cov kev kho mob nrog cov txiaj ntsig tau zoo hauv vivo cov kev tshawb fawb rau hauv daim ntawv thov kho mob uas muaj peev xwm.

ADVANCING CLINICAL trials of STEM CellS FOR KIDNEY DISEASE

Txog rau Lub Peb Hlis 2021, ntau dua 40 qhov kev sim tshuaj, tsis tu ncua lossis ua tiav, suav nrog kev siv cov qia cell-based kho hauv kev kho mob.kab mob raumtau sau npe hauv Tebchaws Meskas Lub Tsev Qiv Tshuaj Kho Mob (ClinicalTrials.gov). Feem ntau ntawm cov kev sim tshuaj tua kab mob raum no siv MSCs hauv lawv txoj hauv kev. Table 1 tau qhia txog cov kev sim ua tiav ntawm MSC- thiab EPC-raws li kev kho mob hauvkab mob raum.

Thawj ob peb qhov kev sim siv MSCs los ntawm cov ntaub so ntswg sib txawv (pob txha pob txha, adipose, umbilical qaum, thiab lwm yam) txawm tias autologously los yog allogeneic ally qhia tias cov hlwb no tuaj yeem muab rau tib neeg. Txawm li cas los xij, qhov ua tau zoo ntawm MSCs los khokab mob raummuaj cov txiaj ntsig sib xyaw. Hauv ib txoj kev tshawb fawb, cov neeg mob uas muaj kev pheej hmoo siab tom qab kev phais AKI thiab tau txais kev phais plawv ib txhij tau txais allogeneic BM-MSCs. Cov neeg mob tau nyob hauv tsev kho mob luv dua thiab tsis xav tau kev nyeem ntawv. Kev tswj hwm BM-MSCs tsis muaj qhov cuam tshuam tsis zoo thiab tiv thaiv cov neeg mob thaum ntxov thiab lig tom qab kev phais lub raum tsis zoo. Txawm li cas los xij, Swaminathan et al tau tshaj tawm qhov kev pom sib txawv, uas yog kev tswj hwm ntawm allogeneic MSCs tsis txo lub sijhawm rov qab los ntawm lub raum ua haujlwm hauv cov neeg mob uas muaj theem ntawm AKI tom qab kev phais plawv. Lawv kuj tseem tsis tau pom qhov sib txawv tseem ceeb ntawm cov pab pawg kho nrog allogeneic MSCs thiab cov pab pawg kho nrog cov placebo hauv 30-hnub kev tshawb fawb txog kev tuag tag nrho. Txawm hais tias tus nqi ntawm cov xwm txheej tsis zoo tsis txawv ntawm pawg, MSC infusion muaj kev nyab xeeb thiab zam tau zoo.

Ntau tus tib neeg tau sim siv MSCs los kho CKD. Ib txoj kev tshawb fawb soj ntsuam kev nyab xeeb thiab kev soj ntsuam muaj peev xwm ntawm autologous kev tswj hwm ntawm AD-MSCs rau cov neeg mob CKD tau tshaj tawm tias cov hlwb muaj kev nyab xeeb thiab tsis ua rau muaj kev phom sij. Nyob rau tib lub sijhawm, kev txhim kho hauv cov zis protein tawm tau pom. Txawm li cas los xij, Makhlough thiab al tau tshaj tawm tsis muaj kev hloov pauv tseem ceeb hauv kev kwv yees glomerular pom tus nqi thiab SCr thaum lub sijhawm 18 mo ntawm kev soj ntsuam tom qab autologous BMMSCs tau hloov pauv hauv cov neeg mob CKD no.

Hauv kev tshawb fawb txog kev kho mob ntawm cov kab mob autoimmune xws li kab mob lupus erythematosus (SLE) nrog MSCs, cov hlwb raug tshawb xyuas rau lawv cov txiaj ntsig kho. Sun L thiab pab pawg tau ua theem I / II kev sim tshuaj ntsuam xyuas cov teebmeem ntawm allogeneic BM-MSCs thiab UC-MSCs infusions hauv cov neeg mob uas muaj thawj thiab refractory SLE. Lawv pom tias qhov kev tso dej ntawm ob qho allogeneic BM-MSCs lossis UC-MSCs muaj kev nyab xeeb thiab ua tau zoo. Dhau li ntawm kev txhim kho SLE Disease Activity Index thiab lub raum ua haujlwm, qib ntawm proteinuria poob qis 24 teev tom qab hloov MSCs. Tsis tas li ntawd, ntawm cov neeg mob SLE, kev hloov pauv ntawm Allogeneic MSCs ua rau lub raum tso tawm rau cov neeg mob LN nquag nyob rau hauv ib lub sijhawm 12-mo tom qab. Barbado thiab al nyob rau hauv lawv txoj kev tshawb nrhiav tau qhia txog kev txhim kho ntawm cov proteinuria thaum thawj lub hlis tom qab kho. Cov kev hloov pauv tau txhawb nqa thoob plaws lub sijhawm rov qab los ntawm cuaj lub hlis. Conversely, ib tug tsis ntev los no multicentre randomized, ob-dig muag tswj mus sib hais pom tau hais tias UC-MSCs tsis muaj qhov tshwm sim ntxiv tshwm sim dua thiab siab dua tus qauv kev tiv thaiv kab mob.

Muab cov cuab yeej immunomodulatory ntawm MSCs, cov hlwb no tau hloov pauv hauv cov neeg mob uas tau txais kev hloov hauv lub raum los txhawb kev tiv thaiv kab mob raum hloov mus rau hauv qhov chaw ntawm peri-transplant T cell-depleting induction therapy. Cov ntawv ceeb toom tau pom tias kev hloov pauv MSCs muaj kev nyab xeeb thiab tsis muaj kev phiv loj txawm tias dhau mus ntev. Tsis tas li ntawd, muaj kev nce ntxiv ntawm Treg tau sau tseg, nce ntxiv hauv kev tswj hwm T cell feem, thiab txhim kho kev ua haujlwm thaum ntxov. Tib lub sijhawm, cov hloov pauv MSCs tseem tswj hwm lub cim xeeb CD8 ntxiv rau T hlwb cov haujlwm thiab txo cov neeg pub dawb tshwj xeeb CD8 ntxiv rau T cell cytolytic teb. Tsis tas li ntawd, MSCs infusion tau pom qhov qis dua ntawm kev tsis lees paub uas ua rau muaj kev pheej hmoo ntawm kev kis tus kab mob tsis zoo thiab ua rau lub raum ua haujlwm sai dua li kev tswj hwm. Cov ntaub ntawv ua ntej no qhia tias kev hloov pauv ntawm MSCs muaj kev nyab xeeb, muaj kev tiv thaiv zoo, thiab tuaj yeem tiv thaiv lub cev tiv thaiv kab mob tom qab hloov lub raum nrog kev sib xyaw ntawm cov tshuaj tiv thaiv kab mob tsim nyog.

Ib theem tsis ntev los no kuv sim siv autologous CD34 ntxiv rau EPCs hauv kev kho CKD ntawm theem III lossis IV tau tshaj tawm. Yip HK thiab pab pawg tau ua pov thawj tias kev hloov pauv hauv lub raum hauv lub raum ntawm CD34 ntxiv rau EPCs muaj kev nyab xeeb thiab zam tau zoo. Txawm li cas los xij, thaum qhov ua tau zoo nyob rau theem II randomized tswj kev sim tau tshawb xyuas ntxiv, cov EPCs infused tsis muaj txiaj ntsig ntxiv rau cov neeg mob nrog CKD txog rau lub sijhawm ua raws li 12 lub hlis. Txawm hais tias qhov kev txhawb nqa tsawg dua, nws tsim nyog sau cia tias qhov txiaj ntsig tsis zoo, xws li kev lim ntshav lossis kev tuag, tau qis dua hauv pab pawg kho mob dua li cov hauv pawg tswj hwm. Tam sim no, ntau qhov kev sim tshuaj tseem tab tom ua thiab yuav muab kev nkag siab ntau ntxiv rau thiab tej zaum yuav txhawb nqa cov kev ua tiav no nrog kev kho mob ntawm tes raukab mob raum. 

XAIV

Txawm hais tias cov kev kho mob qia cell hauv lub raum rov tsim dua tshiab los ntawm kev tshawb fawb hauv vitro thiab preclinical tau cog lus tseg, thiab kev txhawb nqa kev nyab xeeb tau pom nyob rau hauv cov kev sim tshuaj tib neeg thaum ntxov, cov kev kho mob ntawm tes tseem tsis tau muab txhais ua pov thawj tseem ceeb ntawm kev kho mob. Cov kev mob tshwm sim ntawm qia cell kho raukab mob raumtseem xav tau kev tshawb nrhiav ntxiv, vim tias cov txiaj ntsig ua ntej muaj tseem tsis muaj cov ntaub ntawv rov qab mus ntev. Qee qhov kev txhawj xeeb txog kev siv cov qia hlwb nyob hauv yuav tsum tau saib xyuas. EVs kuj tseem yuav raug soj ntsuam raws li qhov ua tau zoo rau cov qia hlwb nyob. Kev siv cov qia hlwb-los ntawm EVs uas tuaj yeem ua raws li lawv cov niam txiv lub hlwb cov teebmeem hauv kev tiv thaiv rov qab tuaj yeem ua raws. Txawm li cas los xij, nws zoo nkaus li tias kev kho cov qia cell yuav muaj lub neej yav tom ntej zoo hauv kev tsim kho lub raum. Cov lus qhia ntxiv yuav tau txais ntawm cov qia hlwb 'kev tiv thaiv mechanisms hauv kev kho mobkab mob raumlos ntawm kev nkag siab ntxiv txog cov txheej txheem ntawm cov qia hlwb ua haujlwm hauv vivo. Txoj kev vam meej ntawm txoj kev kho mob ntawm tes tshiab no tuaj yeem hloov pauv lub neej yav tom ntej ntawm cov tshuaj kho dua tshiab.

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