Tswvyim Ntawm Qe/progenitor Cell Therapy Rau raum Injury
Mar 22, 2022
Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791
PART Ⅳ: qia / progenitor cell hauv lub raum: yam ntxwv, homing, kev sib koom tes, thiab kev saib xyuas
Jiewu Huang, Yaozhong Kong, Chao Xie, thiab Lili Zhou
NYEEM NO PART Ⅲ
Kev kho ua ntej
Tom qabraumraug mob, BMSCs, EPCs, HSCs, thiabraumqia / progenitor hlwb tsiv mus rau hauv cheeb tsam raug mob, tab sis lub cheeb tsam microenvironment kuj tuaj yeem ua rau lawv cov apoptosis vim yog ischemia, o, tsis muaj oxygen thiab khoom noj khoom haus, thiab kev txhawb nqa ntawm oxidative kev nyuaj siab nrog rau kev tiv thaiv kev tiv thaiv kab mob. Cov kev tshawb fawb tau pom tias kev ua haujlwm ntawm EPCs thiab BMSCs hauv CKD yog qhov tsis zoo [200-202]. Undoubtedly, kev ua tau zoo ntawm qia / progenitor hlwb feem ntau nyob ntawm lawv lub peev xwm los mus rau hauv cov chaw raug mob thiab lawv lub sijhawm muaj sia nyob. Ib lub tswv yim los txhim kho qia cell homing thiab ciaj sia taus zoo li tsim nyog.
Stem cell preconditioning yog ib txoj hauv kev zoo rau peb. Cov tswv yim no muaj xws li incubation los yog co-txhaj tshuaj nrog cytokines los yog tshuaj compounds, hypoxia stimulation, thiab genetic hloov [203]. Hypoxic lossis ultrasound preconditioning, incubation nrog TGF- 1 lossis IGF-1, thiab kev txhaj tshuaj nrog erythropoietin tuaj yeem ua rau muaj kev nthuav qhia ntawm CXCR4 hauv BMSCs, ntxiv txhawb BMSC homing rauraumlos ntawm CXCR4/SDF-1 axis[128,168, 204-210]. Leflunomide kuj ua rau kom muaj kev sib koom ua ke ntawm BMSCs, HSCs, thiab EPCs hauv cov ntshav peripheral thiab txhawb nqa lawv cov mi-gration rau hauv cov ntshav.raug mobraum[211]. Hypoxic pre-conditioning upregulates cov kev qhia ntawm CXCR7 nyob rau hauv BMSCs [212], thiab tsis tsuas yog txhim kho BMSC chemo-taxis tab sis kuj txhim khu kev tso tawm ntawm cov tshuaj soluble yam, xws li VEGF, IGF-1, HGF, FGF, thiab angiopoietin thiab nce cell viability hauv cheeb tsam raug mob [128,159,213]. Preconditioning nrog sevoflurane kuj tuaj yeem tsim kev tiv thaiv ntawm BMSC txoj sia nyob los ntawm kev txo qis apoptosis thiab rov ua kom poob ntawm mitochondrial membrane peev xwm [214]. Erythropoietin tsis tuaj yeem txhim kho kev loj hlob ntawm lub raum thiab lub raum kev ua haujlwm ntawm BMSCs [215,216] tab sis kuj tseem tiv thaiv cov kab mob.raumlos ntawm kev txhim kho kev nthuav dav thiab nrhiav neeg ua haujlwm ntawm EPCs [217,218]. Statin pretreatment ameliorates oxidative kev nyuaj siab, inhibits inflammatory teb nyob rau hauv lub raum raug mob, tsub kom ciaj sia ntawm implanted BMSCs [219], thiab kuj nce EPC recruitment, thiab txo apoptosis [220]. Kev kho BMSCs ua ntej nrog melatonin txhim kho lawv txoj sia nyob tom qab tsiv teb tsaws mus rau hauv lub raum raug mob [221, 222]. Kev tswj hwm ntawm pioglitazone tuaj yeem txhim kho txoj haujlwm ntawm MSCs thiab EPCs los ntawm kev txo qis endo-plasmic reticulum stress thiab mitochondrial fusion [223-226]. Kev kho mob ua ntej nrog dipeptidyl peptidase-4 inhibitor sitagliptin, tus neeg sawv cev rau kev kho mob incretin-based rau hom 2 mob ntshav qab zib mellitus, tuaj yeem txhim kho EPC mobilization los ntawm kev nce plasma SDF-1 concentrations, tejzaum nws yog lub tswv yim zoo rau Kev kho mob ntshav qab zib nephropathy [228].
Kev hloov kho noob caj noob ces kuj yog ib txoj hauv kev zoo ntawm preconditioning los txhim kho qia cell homing rau lub raum. CXCR4-overexpressing BMSCs tsim los ntawm lentivirus kab mob muaj peev xwm muaj zog nyob rau hauv tsev rau lub raum thiab txhim kho paracrine yeeb yam los tsim HGF, BMP-7, thiab cov anti-inflammatory cytokine IL-10 [229 ]. Kallikrein-hloov BMSCs los ntawm lentivirus kab mob kuj muaj zog tiv thaiv oxidative, anti-apoptotic, anti-inflammatory, thiab angiogenic cuam tshuam rau lub raum raug mob [230].MiR-let7c-overexpressing BMSCs tuaj yeem xa ntau miR-let7c los ntawm EVs mus rau lub raum raug mob, txuas ntxiv txo qhov kev qhia ntawm cov noob caj noob ces fibrosis thiab lub raum fibrosis [231]. MiR-126-kev tshaj tawm BMDCs muaj peev xwm txhim kho mus rau hauv cov chaw raug mob los ntawm kev tswj hwm CXCR4/SDF-1 axis [232].
cistanche pharma tshwj xeebrauraum
Daim ntawv thov ntawm bioactive molecules secreted los ntawm qia / progenitor cells
Raws li tau piav qhia saum toj no, ntau cov kev tshawb fawb qhia tau hais tias cov bio-active molecules secreted los ntawm qia / progenitor hlwb kuj ua lub luag haujlwm tseem ceeb hauv kev kho lub raum ua haujlwm. Lawv daim ntawv thov tuaj yeem muaj ntau yam zoo hauv kev siv tshuaj kho mob, suav nrog kev tiv thaiv cov qia / progeni-tor hlwb los ntawm kev tshawb nrhiav ncaj qha rau microenvironment raug mob thiab ua kom yooj yim tsim khoom thiab txheej txheem cia [233]. Kev ua haujlwm ntawm qia hlwb hauv CKD yog qhov tsis zoo, thiab cov qia hlwb tuaj yeem raug tsis lees paub, yog li kev siv bioactive molecules secreted los ntawm qia hlwb yog lub tswv yim muaj peev xwm los daws qhov teeb meem no. Raws li txoj cai, cov kev kho mob tsis muaj cell yuav pom muaj kev nyab xeeb zoo dua piv nrog kev xa cov qia hlwb ncaj qha. BMSC-derived conditioned nruab nrab txhawb kev tsim kho ntawm lub raum raug mob, txo lub raum mob thiab fibrosis, thiab rov khaws cov qauv microvascular hauv unilateral ureteral obstruction (UUO), 5/6 nephrectomy, thiab mob ntshav qab zib nephropathy qauv[48, {{9} }]. Cov txiaj ntsig ntawm EVs los ntawm BMSCs ntawm kev rov qab los ntawm lub raum zoo ib yam li kev tswj hwm-tration nrog BMSCs, yog li kev siv EVs kuj yog ib lub tswv yim zoo rau peb. Cov kev tshawb fawb qhia tau hais tias allogenic raum-nyob hauv MSC-derived EVs tuaj yeem txo qis apoptosis, txhim kho tubular proliferation thiab tubule tsim, thiab txo cov cell infiltration hauv IRI thiab UUO qauv [170, 237]. Tsis tas li ntawd, ob qho tib si autologous thiab allogeneic BMSC-derived EVs tuaj yeem txhim kho lub raum ua haujlwm hauv IRI, tshuaj tiv thaiv nephropathy, UUO, thiab subtotal nephrectomy qauv [169,177,178,238-241].
cistanche tshuaj ntsuabtuaj yeem kho mob raum kom zoolub raum ua haujlwm
Biomaterials
Biomaterials, uas tuaj yeem txhim kho kev tsiv teb tsaws ntawm qia/progenitor hlwb, txhim kho lawv txoj haujlwm, thiab muab cov microenvironment zoo, yuav tsum tau muab rau hauv kev txiav txim siab [242]. Raws li tau piav qhia saum toj no, bioactive molecules secreted los ntawm qia hlwb muaj ntau yam zoo hauv kev ua kom lub raum ua haujlwm, tab sis lawv tsis ruaj khov thiab sai sai hauv vivo. Yuav kom tswj tau cov ntshav siab, yuav tsum muaj ntau txoj cai. Bio-cov ntaub ntawv xws li hydrogel, uas ua kom muaj kev tswj xyuas rov ua dua ntawm cov khoom siv bioactive, tuaj yeem daws qhov teeb meem no [243]. EVs kuj tseem yuav tsum tau noj ntau zaus vim tias lawv tau tshem tawm sai ntawm lub cev los ntawm cov kab mob reticuloendothelial tom qab txhaj tshuaj rau hauv kev ncig [244]. Preconditioning nrog biomaterials yog ib lub tswv yim zoo los kov yeej kev tshem tawm sai. Kev sib xyaw lossis qhwv EVs hauv biomaterial matrix tuaj yeem tswj hwm lawv cov bioavailability tom qab kev tswj hwm, tso cai rau kev tso tawm thiab tswj hwm, txhawm rau txhim kho kev ua tau zoo[159]. Hydrogels, tshwj xeeb tshaj yog hloov hydrogels, tuaj yeem txhim kho kev tuav thiab ruaj khov ntawm EVs [245]. Ib txoj kev tshawb fawb qhia tau hais tias ib hom mesoscale nanoparticles tuaj yeem ntim cov khoom me me thiab txawm tias cov biomolecules loj xws li DNA uas tsis nyob ntawm cov khoom thauj khoom thauj khoom thiab nthuav tawm 26-fold raum xaiv yam tsis muaj kev phiv xws li kev tiv thaiv kab mob thiab lub siab lossis lub raum tsis zoo. [246]. Preconditioning nrog biomaterials kuj tuaj yeem txhim kho qia cell ciaj sia, engraftment, thiab homing. Kev txhaj tshuaj biomaterials xws li hydrogels tuaj yeem ua rau kom cov qia hlwb tom qab hloov pauv [242]. MSC spheroids nkag rau hauv Arg-Gly-Asp-hloov alginate hydrogels pom tias txo qis apoptosis thiab nce kev ciaj sia ntxiv nrog rau VEGF tso tawm tom qab hloov pauv [247]. Tsis tas li ntawd, txoj hmoo ntawm qia / pro-genitor cells homeing rau cov chaw raug mob feem ntau yog nyob ntawm thaj chaw microenvironment. Cov khoom siv biomaterials tuaj yeem muab cov qia cell niche zoo li microenvironment rau transplanted qia/progenitor cells hauv vivo[159]. Preconditioning ntawm pro- ciaj sia taus peptides nrog ib tug qeeb-tso tawm ntawm collagen matrix yuav txhim khu kev ciaj sia ntawm BMDCs tom qab ischemic raug mob [248]. Porous alginate cryogels, cov khoom siv hluavtaws, tuaj yeem txhim kho cov teebmeem paracrine ntawm MSCs [249]. Tsis tas li ntawd, kev siv biomimetic macroporous polyethylene glycol hydrogel yog ib txoj hauv kev zoo los txhawb kev sib npaug ntawm HSCs ua ntej hloov pauv hauv vitro los ntawm kev ua raws li lub ntuj microenvironment ntawm HSCs [250].
cistanche cog
Cov txheej txheem bioengineering
Bioengineering tej zaum yuav yog ib lub tswv yim zoo los hloov lub raum raug mob yav tom ntej. Kitamura et al. pom tias lub raum qia/progenitor hlwb nyob rau hauv S3 ntu muaj peev xwm rov tsim tau peb-dimensional nephron-zoo li qauv hauv vitro [72]. Ntxiv mus, muaj peb lub ntsiab proto-cols los ntxias tib neeg lub raum organoids tsim los ntawm lub raum progenitor hlwb los ntawm ESCs los yog induced pluripotent qia hlwb (iPSCs) [251]. Thawj txoj cai, muab tso rau pem hauv ntej los ntawm Taguchi li al, uas tau tshwm sim los ntawm kev tsom xam ntawm embryonic lub raum precursor cell pejxeem, tsim lub raum progenitor cell-based raum organoids los ntawm ESCs los yog iPSCs [252]. Taguchi raws tu qauv induces ESCs los yog iPSCs rau hauv lub raum progenitor hlwb, uas tom qab ntawd generates lub raum tubules thiab glomerulus zoo li cov qauv, thiab ua tau zoo vascularized tom qab transplantation [253]. Cov txheej txheem thib ob, hu ua Takasato raws tu qauv, siv ob-dimensional induction ntawm lub raum progenitor hlwb, ua raws li peb-dimensional kab lis kev cai, tsim rau lub raum organoids uas muaj nephrons, sau ducts, thiab interstitium, raws li zoo raws li endothelial hlwb, raws li kev saws. ntawm ESCs lossis iPSCs. Lub raum organoids muaj peev xwm nqus tau rau dextran [254-256]. Txoj cai thib peb, Morizane raws tu qauv, zoo li Takasato raws tu qauv, muab faib ua ob sab thiab peb-dimensional cov kauj ruam, tab sis yuav tsum tau siv sij hawm tsawg, los tsim cov organoids uas muaj epithelial nephron zoo li cov qauv [257].ESCs/iPSC-derived functional raum. organoids, uas tuaj yeem muab tau los ntawm cov neeg mob tus kheej lub hlwb, tam sim no muaj peev xwm zoo rau kev kho mob raum rau yav tom ntej [258]. Txawm li cas los xij, muaj ntau yam kev sib tw uas yuav tsum tau kov yeej ua ntej kev thov ntawm cov menyuam yaus organoids hauv tib neeg, suav nrog cov tswv yim los txhim kho qhov scalability thiab vascularization ntawm organoids. Tsis tas li ntawd, nws tau pom tias cov hlwb hauv lub raum organoids tsis paub tab ntau dua li cov hlwb hauv cov neeg laus lub raum, thiab muaj cov hlwb uas tsis yog lub raum nyob hauv organoids [251].
Daim ntawv thov ntawm decellularized extracellular matrix (ECM) scaffold, muab 3D ib puag ncig ua raws li cov ntaub so ntswg. Cov ntaub ntawv uas suav nrog gels, thaj ua rau thaj, ntu, blocks, thiab txheej txheej, kuj tseem yuav ua lub luag haujlwm tseem ceeb hauv cov tshuaj kho dua tshiab thiab bioengineering yav tom ntej [242].ECM scaffolds los ntawm lub raum, uas tsis muaj cov hlwb lossis tseem ceeb hauv cell-associated immunogenic. cov cim, tab sis tsuas yog ib haiv neeg lub raum architecture thiab extracellular matrix protein, tsim ib lub niche zoo ib yam li lub raum cov ntaub so ntswg, pab txhawb kev recruitment ntawm qia / progenitor hlwb, txhim khu neovascularization, thiab txhawb kev kho ntawm lub raum kev ua haujlwm [259,260].dECM scaffolds los ntawm porcine, khaws cia cov neeg lub raum architecture, extracellular Cheebtsam, thiab ib tug tsis tu ncua vasculature network, tej zaum ib tug promising plat-form rau lub raum bioengineering vim lub raum tsis muaj peev xwm hloov kho [261]. SDS-kho ECM scaffolds los ntawm porcine qhia tsis muaj cytotoxicity rau thawj tib neeg lub raum hlwb thiab kev nyuaj siab immunoreactivity los ntawm tag nrho clearance ntawm porcine cellular khoom [262]. Ib txoj kev tshawb fawb qhia tau hais tias tom qab cog cov porcine dECM scaffold rau hauv lub raum porcine, lub scaffold tau yooj yim reperfused, tuaj yeem txhawb nqa ntshav siab, thiab raug zam rau lub sijhawm kawm yam tsis muaj ntshav ntxiv. Txawm li cas los xij, cov kab mob inflammatory thiab ua tiav thrombosis kuj tuaj yeem pom [263].Hauv kev tshawb fawb, cov kws tshawb fawb cog nas ESCs hauv dECM scaffolds ntawm nas raum kom induce recellularization thiab organoid con-structure nyob rau hauv vitro thiab ces cog rau hauv ib tug uninephrec-tomized nas. . Qhov tshwm sim qhia tau hais tias cov recellularized scaffolds tau yooj yim reperfused, tuaj yeem tiv taus cov ntshav ua ntej, thiab tsim cov zis uas tsis muaj ntshav tawm rau kwv yees li 2 lub lis piam [264]. Txawm hais tias kev rov tsim dua tshiab ntawm tag nrho cov khoom nruab nrog cev tsis tau ua tiav thiab muaj ntau yam teeb meem tseem yuav tsum tau kov yeej, kev sib xyaw ntawm cov qia / progenitor cells thiab ECM scaffolds yuav vam tias yuav kov yeej cov teeb meem no ib hnub thiab ua ntej hauv cov tshuaj regenerative [265].
dab tsi yog cistanche
