学科分类
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162 个结果
  • 简介:ToobservepotentialeffectoftheengineeredbonemarrowstromalcelllineQXMSC1secretingIL-6(QXMSCIL-6)onacceleratingimmnunereconstitutioninsyngeneicbonemarrowtransplantationinmice,QXMSC1wastransfectedwiththeeukaryocyticexpressionvectorpcDNAIL-6,whichcontainedhIL-6cDNAbyliposome-mediatedgenetransfectingtechnique.G418-resistanceclonewasselectedbylimitingdilution.ThehighestsecretingclonewasselectedbyELISAassayandusedinanimalexperiments.Therecipientmice(BALB/c)werelethallyirradiatedandcotransplantedsyngeneicbonemarrow(10^7/mice)andtheQXMSCIIL-6(5×10^5/mice).LymphocyteproliferationinducedbyConAandLPS,helperTlymphocyteprecursor(HTLp),cytotoxicTlymphocyteprecursor(CTLp),plaque-formingcell(PFC),delayedtypehypersensitivity(DTH)wereexamined30,60daysinposttransplantationrespectively.TheresultsshowedthatlymphocytesproliferationtoConAandLPS,HTLp,CTLpincreased,DTHandPFCwereimprovedbycograftedstromalcellsQXMSCIIL-6on30,60daysafterBMT.TheseresultsdemonstratedthatthebonemarrowstromalcelllineQXMSC1IL-6transfectedwithIL-6(QXMSC11L-6)acceleratedimmnunereconstitutioninsyngeneicbonemarrowtransplantation.

  • 标签: 基因转染 IL-6基因 骨髓基质细胞系 骨髓移植 免疫功能 基因疗法
  • 简介:Objective:Toinvestigateanewmethodtoconstructtissue-engineeringbonethatwillbeapplicableclinically.  Methods: Thecultured5thgenerationrabbitbonemarrowstromaosteoblasts(MSO)wasdissolvedin3%sodiumalginatesolution(thefinalconcentrationofsodiumalginateinthesolutionbeing1%,andMSO,5×106/L),andtheninoculatedintopreparedtrueboneceramic(TBC)andgelatinizedthebonebydribblingwithcalciumgluconate.Thestandardbonedefectmodelsweremadein48adultNewZealandrabbitsbothradius.Amongthe48rabbits,24wereinGroupsAandB,inwhichtheleftradiuswasimplantedwithgelatinizedMSO-TBC(GroupA)andrightradiusimplantedwithautograft-bone(GroupB);andtheother24wereincontrolgroupwhoseleftradiuswasimplantedwithnon-gelatinizedMSO-TBC(GroupC)andrightradiusimplantedwithgelatinizedTBC(GroupD).Outcomesoftheimplantedboneswereassessedbyradiology,pathologicalhistology,osteogeneticquantitativeanalysis,andbiomechanicsat2,4,8,12weekspostoperatively.Results: InGroupsAandB,asatisfactorybonereparationandbonyunionwasnotedwithin12weeks.InGroupsCandD,bonereparationwasnotsatisfiedcomparedwithGroupAintermsofostogeneticquantityandbiomechanics. Conclusions: GelatinizedMSO-TBCisanidealartificialactivebonethatovercomesTBCshortcomingsoffragilenessandsmoothsurfacethatisnoteligibleforseedcellsadhesion.Itispromisingtoputintoclinicaluseextensively.

  • 标签: 骨髓胶基质 MSO-TBC 人工骨 临床应用 生物材料
  • 简介:间充质的干细胞(MSC),源于成年纸巾,是multipotentprogenitor房间,它为再生药保持大诺言。最近的研究证明了thatMSCs在动物和人是抑制免疫力的体内和试管内。然而,管理MSC的这些有免疫力的调节功能的机制留下大部分逃犯。有MSC的体积人口的一些研究显示象PGE2和TGFbeta那样的可溶的因素是重要的,当其它为房间房间接触支持一个角色时。在这研究,我们打算由检验克隆的MSC的抑制免疫力的效果澄清这些问题。我们从老鼠骨髓导出MSC克隆并且证明这些克隆的多数能区分进adipocytes象andosteoblast一样房间。重要地,从这些克隆的房间展出了强壮的禁止的效果onTCR这些房间的一个小数字的导致激活的T细胞增殖试管内,和注射在老鼠支持了allogeneic皮肤接枝的幸存。从MSC文化的调节媒介证明anti-CD3上的某禁止的效果导致了独立于PGE2andTGFbeta的淋巴细胞增长。在比较,有刺激淋巴细胞的MSC的直接合作文化导致了许多更强壮的抑制免疫力的效果。有趣地,抑制是双向的,当MSCproliferation也面对淋巴细胞被减少。一起拿,我们有克隆的MSC的调查结果证明这些房间通过可溶的因素和房间房间施加他们的抑制免疫力的效果接触,和那淋巴细胞和MSC在他们的各自的增长上是互相禁止的。

  • 标签: 骨髓间质细胞 克隆 干细胞移植 免疫抑制 细胞因子
  • 简介:ThelyricsoftranscendencebyWilliamButlerYeatsistoagreatextentacomprehensiveinterpretationofYeats’viewsonpoeticsandlife.AccordingtoYeats,transcendenceisessentiallyacold,loftywisdomwithwhichhumanbeingscouldtranscendtheirinnatelimitations,incompletenessaswellasthesecularitiesofexistence,thereforeachievingthemasteryoverone’sfate.ThethematicstudyofYeats’lyricsoftranscendenceoffersanuniqueapproachtoYeats’philosophyinartandlife.

  • 标签: Yeats LYRICS TRANSCENDENCE
  • 简介:骨头髓(BM)的细胞的基础织物开发和新生通过造血的干细胞(HSC)和间充质的干细胞(MSC)被调停。在造血的房间和BMstromal房间(BMSC)之间的本地相互影响在myelosuppression以后决定造血作用的体质。这里,我们在侮辱以后控制BM新生考察BM本地信号。造血的生长因素(HGF)和BMSC生产的cytokines是在BM造血作用的规定的主要因素。对在多重种类的早胚胎开发批评的Morphogens被加到HSC管理者的家庭,包括Wnt蛋白质,槽口ligands,BMP,和刺猬的家庭。HSC和BMSC的全球基因表示分析开始为两种房间类型揭示了基因的签名组。更重要地,生物化学、生物的结合的全球基因表示的分析在BM期间本地信号学习新生强烈建议了HGF和cytokines不能是为BM恢复的主要本地管理者,chemokines(SDF-1,FGF-4)并且angiogenic生长因素(VEGF--一,Ang-1)在myelosuppression以后在BM宪法起有启发性的作用。BM毒性的管理的一个新方向从BM再生管理者的鉴定正在出现。

  • 标签: 干细胞 骨髓再生 病理机制 间叶细胞
  • 简介:AbstractImportance:Burkitt lymphoma with bone marrow involvement and Burkitt leukemia behave aggressively. Thus far, there are limited data concerning survival and toxicity in Chinese children with Burkitt lymphoma or Burkitt leukemia who have undergone treatment with the non-Hodgkin’s lymphoma Berlin-Frankfurt-Münster-90/95 (NHL-BFM-90/95) protocol.Objective:To analyze outcomes and toxicity in pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia following treatment with the NHL-BFM-90/95 protocol.Methods:Patients aged <18 years with bone marrow involvement/leukemia who were treated with the NHL-BFM-90/95 protocol, with or without rituximab, in Sun Yat-Sen University Cancer Center from April 2004 to December 2018 were included in this retrospective analysis.Results:Twenty-five patients were eligible. Burkitt lymphoma with bone marrow involvement and Burkitt leukemia were present in 10 and 15 patients, respectively. Central nervous system infiltration was not observed in any patients. All patients underwent chemotherapy involving NHL-BFM-90/95 protocol. Six courses of treatment were administered to each patient (v-AA-BB-CC-AA-BB-CC). The BFM-90/95 plus rituximab protocol was administered to 13 patients. The median follow-up interval was 31.9 months (range, 2.5-158 months). Of the 25 patients, four died: three died of tumor progression and one died of therapy abandonment after relief of tumor lysis syndrome. The estimated 5-year event-free survival and overall survival rates were both 85.8% ± 5.0%.Interpretation:Chinese pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia can achieve optimal treatment outcomes and exhibit good tolerance when using the NHL-BFM-90/95 protocol.

  • 标签: Burkitt lymphoma Bone marrow Burkitt Leukemia B-Cell Prognosis
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  • 简介:Tostudytheosteogenicabilityoftissue-engineeredboneconstructedbycompoundingzinc-sin-teredbovinecancellousbonewithrabbitmarrowstromalcells(MSCs)invivo,thezinc-sinteredbovinecancellousboneofbeta-tricalciumphosphate(TCP)typewaspreparedbysinteringthefreshcalfcancellousbonetwiceandthenloadingitwithzinc-ion.TherabbitMSCswerecultured,inducedandseededontothezinc-sinteredbovinecan-cellousbones.Thetissue-engineeredboneswerethenimplantedintotherabbits'bockmuscles.Thenewlyformedbonetissueswereobservedbyhistologicalmethodsandtheareasofnewosseoustissuesweremeasuredattheendofthe4thand8thweek.Thezinc-sinteredbovinecancellousbonesalonewereimplantedontheothersideascontrol.TheosteogenicactivityofMSCswasidentifiedbyalkalinephosphatase(ALP)stainingandcalcificationnodchi-nalizarinstaining.Attheendof4thweek,asmallamountofnewbonetissueswasobserved.Attheendof8thweek,thereweremanynewlyformedbonematuretissues.Moreover,theareaofthelatterwassignificantlylargerthanthatoftheformer(P<0.01),whileinthecontrolgrouptherewasnonewboneformation.Thetissue-engi-neeredbone,whichwasconstructedbycombiningzinc-sinteredbovinecancellousbonewithMSCs,hassatisfactoryosteogeniccapabilitiesinvivo.

  • 标签: 松质骨 骨髓基质细胞 成骨稳能力 MSCs Β-磷酸三钙 骨组织工程
  • 简介:Objective:Toevaluatetheosteogenicpotentialofbonemorphogeneticprotein(BMP)-2genetransfectedgoatbonemarrow-derivedmesenchymalstemcells(MSCs).Methods:Goatbonemarrow-derivedMSCsweretransfectedbyAdv-humanbonemorphogeneticprotein(hBMP)-2gene(Group1),Adv-betagaltransfectedMSCs(Group2)anduninfectedMSCs(Group3).Westernblotanalysis,alkalinephosphatasestaining,VonKossastainingandtransmissionelectronmicroscopywereadoptedtodeterminethephenotypeofMSCs.Thenthecellswereinjectedintothighmusclesofthenudemice.Radiographicalandhistologicalevaluationswereperformedatdifferentintervals.Results:OnlyAdv-hBMP-2transfectedMSCsproducedhBMP-2.Thesecellswerepositiveforalkalinephosphatasestainingatthe12thdayandwerepositiveforVonKossastainingatthe16thdayaftergenetransfer.Electronmicroscopicobservationshowedthatthereweremoreroughendoplasmicreticulum,mitochondriaandlysosomesinAdv-hBMP-2transfectedMSCscomparedtoMSCsofothertwogroups.Atthe3rdand6thweeksaftercellinjection,ectopicboneswereobservedinmusclesofnudemiceofGroup1.Onlyfibroustissueoralittlebonewasfoundinothertwogroups.Conclusions:BMP-2genetransfectedMSCscandifferentiateintoosteoblastsinvitroandinduceboneformationinvivo.

  • 标签: 异位骨形成 骨成形蛋白-2 基因转染 骨髓间充质干细胞 小鼠 动物实验
  • 简介:Duringautologousbonemarrowgraftintreatmentofmalignantdiseases,itiscriticaltopurgemalignantcellsfromthemarrow.Inthepresentstudy,thesensitivitytophotodynamicinactivationof3leukemiccelllineswascomparedwiththeircounterpartnormalhematopoieticcells.AftermouseleukemicL1210cellsweretreatedwithapreparationofhematoporphyrinderivatives,YHpD,10μg/mlfor1hr.andirradiatedwithblacklight(peakwavelength395nm,lightintensity0.6mW/cm2)for5minutes,thesurvivalrateofclonogeniccellsdecreasedto<10%,whilethatofbonemarrowgranulocytemacrophageprogenitorcells(CFU-GM)inDBA/2miceremainedatnearlynormallevel(>80%).SimilarresultswereobtainedwhenhumanleukemicHL-60cellswerecomparedwithhumanCFU-GMandmouseleukemicL615cellswithCFU-GMin615strainmice.ItissuggestedthathematoporphyrinphotoradiationmaybeusefulforIselectivelykillingleukemiccellsinbonemarrow.

  • 标签: PROGENITOR hematopoietic GRANULOCYTE minutes macrophage graft
  • 简介:backgroundBonemarrowmesenchymalstemcells(BMSCs)canbeisolatedandculturedtomanypassages.However,StemcellsincludingBMSCsquicklyundergosenescenceinculture.Thecellsenescenceandmulti-directionaldifferentiationhavehamperedproducingBMSCsinquantitywiththeirundifferentiatedstate.Inthisstudywereportanaturalcompound,vitaminC(Vc),maintainsBMSCsstemproperty.MethodsHumanBMSCswereisolatedfrombonemarrowandpurifiedby1.073g/mLdensitygradientcentrifugation.50ng/mLVcwereaddedtoBMSCsfordifferenttimepoint.FlowcytometrywasusedtodetectcellsurfacemarkersofBMSCswithorwithoutVctreatment.BMSCsproliferationwasanalyzedbyMTTassay.PCR(polymerasechainreaction)andreal-timePCRwereusedfordetectingc-kit,nanog,andOct-4genesexpressionlevels.DNAmethyltransferase(Dnmt)1andDnmt3blevelswerealsodetectedbyreal-timePCR.ResultsFlowcytometryshowedthatafterVctreatmentfor6h,thesurfacemarkersofBMSCswerealmostunchanged.VcincreasedtheproliferationactivityofBMSCsfrom6hto24h.PCRshowedtheexpressionofc-kit,nanog,andoct-4geneswereobviouslyincreasedinVctreatedgroupthancontrolgroupat12h.Real-timePCRshowedthatthelevelofc-kit,nanog,andoct-4geneswereunregulatedfrom6hto12hcomparedwithcontrolgroup.VcalsoincreasedDnmt3bbutnotDnmt1geneexpression.ConclusionsOurresultsshowedVcactsatleastacceleratesBMSCsproliferationandmaintainsstemcellproperty.Inourstudy,wehighlightedamethodofimprovingthespeedofBMSCsgenerationandprovidedadditionalinsightsintothemechanisticbasisofpreventingBMSCssenescence.

  • 标签: 骨髓间质干细胞 维生素C 骨髓基质干细胞 自我更新 骨髓基质细胞 PCR检测
  • 简介:客观:由经皮的解压缩和自体同源的骨头marrowmononuclear房间(BMC)评估大腿骨的头的处理ofosteonecrosis的临床的功效和安全注入。方法;在有在早舞台的脉管的坏死的28个病人的44个臀部由解压缩由自体同源的BMCsinfusion跟随了的经皮的多重洞被对待。自体同源的BMC从从病人的以后的肠骨的冠被拿的骨头髓被集中。病人们在至少2年上面被跟随。结果被变化在radiograghic阶段在哈里斯臀部分数和前进决定。结果:Nocomplications在操作以后被观察。在操作前,有在8个臀部,在15个臀部的阶段Ⅱ,在14个臀部的阶段Ⅲ,在7个臀部的阶段Ⅳ,和在最近的后续的手术后的阶段的大腿骨的头坏死的阶段Ⅰ是在1个臀部的阶段O,在6个臀部的阶段Ⅰ,在13个臀部的阶段Ⅱ,在13个臀部的阶段Ⅲ,在7个臀部的阶段Ⅳ,在4个臀部的阶段Ⅴ。吝啬的preoperativeHarris臀部分数是58(46-89),并且改善了到86(70-94)手术后地。外科手术前地折叠的所有大腿骨的头证明坏死的尺寸是至少超过30%。结论:与自体同源的BMC相结合的经皮的多重洞解压缩是对待大腿骨的头的脉管的坏死的一个新方法。越早阶段,越更好结果。Arandomized未来的学习需要以后与平淡的核心解压缩作比较。

  • 标签: 骨坏死 股骨 经皮减压 自体骨髓 单核细胞
  • 简介:增加的证据在有免疫力的反应显示leptin的一个角色,但是发信号的leptin是否涉及在骨头髓(BM)调整NK房间开发,仍然保持大部分不清楚。在这研究,我们在在prediabetic的缺乏的db/db老鼠上演的leptin受体的BM描绘了NK房间区别和成熟。尽管BM细胞质类似于控制值,NK房间的全部的数字严重地在变异的鼠标被减少。db/dbBM房间的流动cytometric分析揭示了在区别的各种各样的阶段开发NK房间的显著地减少的频率。显著地显示的BMdb/dbNK房间增加了apoptosis,但是维持了正常房间骑车地位和proliferative能力。而且,recombinantleptin能显著地在文化从野类型的老鼠提高NK房间的幸存。NK房间上的进一步的检查功能的活动证明db/dbNK房间与显著地增加的IL-10展出了正常内在的cytotoxicity生产。一起拿,我们的调查结果建议发信号的leptin经由在老鼠BM提高不成熟的NK房间的幸存调整NK房间开发。

  • 标签: 小鼠骨髓 NK细胞 细胞凋亡 瘦素 保护 信令
  • 简介:骨头导出髓的间充质的干细胞(MSC)是为房间移植在临床的应用程序显示出一个重要潜力的pluripotent干细胞。在现在的论文,proteomic技术被用来接近与猪的骨头髓MSC联系的蛋白质侧面并且在5-azacytidine(5-aza)的效果上调查MSC蛋白质的规定。超过1,700蛋白质种类根据胶化分析与MSC被分开。与控制MSC介绍的表达式相比,有起来调整的11个蛋白质点并且26在5-aza-treated房间的蛋白质模式下面调整。21蛋白质的一个总数被MALDI-TOF-MS分析成功地识别,在哪个之中一些有趣的蛋白质,例如高山哈B-crystallin,在A2的附属建筑,和stathmin1,被报导了通过不同发信号的小径在房间增长和区别包含。我们的数据应该为MSC区别和apoptosis的未来学习是有用的。

  • 标签: 5-氮胞苷 基因表达 骨髓干细胞 电泳实验
  • 简介:瞄准:调查角色和骨头髓的潜在的机制在严重尖锐腹膜炎(树液)的间充质的干细胞(MSC)。方法:从SpragueDawley老鼠的胰腺的acinar房间随机被划分成三个组:非钠deoxycholate(SDOC)组(non-SODC组),SDOC组,和MSC干预组织(即,MSC的一个合作文化系统和胰腺的acinar房间+SDOC)。房间幸存率,malonaldehyde(MDA)的集中,superoxidedismutase(草皮)的密度,浆液淀粉酶(AMS)分泌物评价并且喂奶脱氢酶(LDH)漏率在各种各样的时间点被检测。在分开的研究,SpragueDawley老鼠随机被划分成一个树液组或MSC组织的树液+。浆液AMS,MDA和草皮,interleukin(IL)-6,IL-10,和肿瘤坏死因素(TNF)-层次,肠的mucosa损害分数和小肠的mucosa的增殖的房间在注射任何一个MSC以后在各种各样的时间点被测量或进老鼠盐。在两学习,MSC的保护的效果被评估。结果:在vitro,胰腺的acinar房间和草皮的密度的房间幸存率显著地被减少,并且MDA,AMS分泌物率和LDH漏率的集中显著地与MSC干预组和Non-SDOC组相比在SDOC组被增加在每次指。在vivo,在SAP+MSC组的浆液AMS,IL-6,TNF-和疯水平比SAP组低;然而,浆液IL-10水平比SAP组高。浆液草皮水平比SAP组在高每次指,而在草皮水平的重要在组之间差别仅仅在24h以后被注意。肠的mucosa损害分数显著地被减少,小肠的mucosa的增殖的房间在注射MSC以后变得明显。结论:MSC能有效地减轻损害到胰腺的acinar房间和小肠的上皮,支持伤寒上皮的增长并且mucosa修理,与树液一起在老鼠稀释全身的发炎。

  • 标签: 骨髓间充质干细胞 重症急性胰腺炎 大鼠模型 间质干细胞 超氧化物歧化酶 血清淀粉酶
  • 简介:Poly(lactide-co-glycolide)-poly(ethylene乙二醇)-poly(lactide-co-glycolide)(PLGA-PEG-PLGA)triblock共聚物是作为macroinitiator和亚锡的octoate与木钉通过LA和GA的戒指洞聚合被综合催化剂。进在水的答案的微粒自我装配的amphiphilic共聚物,和形成的hydrogels作为在相对高的集中的温度的增加(>15wt%)。hydrogel的有利degradability被证实由在vitro并且在vivo降级实验。好细胞并且thermogel的tissular相容性被表明。骨头髓的优秀粘附和增长间充质的干细胞为软骨织物工程赋予了PLGA-PEG-PLGAthermogellinghydrogel以迷人的前景。

  • 标签: 骨髓间充质干细胞 软骨组织工程 可生物降解 热凝胶 培养基质 三嵌段共聚物
  • 简介:Objective:Toinvestigatethedifferentiativecapabilityofadulthumanbonemarrowmesenchymalstemcells(BMSCs)intoSchwann-likecells.Methods:BonemarrowswereaspiratedfromhealthydonorsandmononuclearcellswereseparatedbyPercolllymphocytesseparationliquid(1.073g/ml)withcentrifugation,cellswereculturedinDMEM/F12(1:1)mediumcontaining10%fetalbovineserum(FBS),20ng/mlepidermalgrowthfactor(EGF)and20ng/mlbasicfibroblastgrowthfactor(bFGF).Cellsofpassage1wereidentifiedwithimmunocytochemistry.Conclusions:BonemarrowcontainsthestemcellswiththeabilityofdifferentiatingintoSchwann-likecells,whichmayrepresentanalternativestemcellsourcesforneuraltransplantation.

  • 标签: 成年 骨髓间充质干细胞 施沃恩样细胞 神经移植
  • 简介:BACKGROUND:Microgliaareverysensitivetoenvironmentalchanges,oftenbecomingactivatedbypathologicalconditions.Activatedmicrogliacanexertadualroleininjuryandrepairinvariousdiseasesofthecentralnervoussystem,includingcerebralischemia,Parkinson’sdisease,andAlzheimer’sdisease.OBJECTIVE:Animmortalmicroglialcellline,BV2,wastreatedwithvaryingconcentrationsoflipopolysaccharide(LPS)toinduceapathologicalsituation.Supernatantwasharvestedandincubatedwithbonemarrowmesenchymalstemcellsand,concomitantly,bonemarrowmesenchymalstemcelldifferentiationwasobserved.DESIGN:Acontrolledobservation,invitroexperiment.SETTING:DepartmentofNeurology,FirstAffiliatedHospitalofChinaMedicalUniversity.MATERIALS:Fivemale2–3-week-oldSpragueDawleyratswerepurchasedfromAnimalLaboratoryCenterofChinaMedicalUniversityandincludedinthisstudy.Theprotocolwasperformedinaccordancewithethicalguidelinesfortheuseandcareofanimals.ThemicroglialcelllineBV2wasproducedbyCellResearchInstituteofChineseAcademyofSciences.LPSwasproducedbySigmaCompany,USA.METHODS:ThisstudywasperformedintheCentralLaboratoryofChinaMedicalUniversityfromSeptember2006toMarch2007.Ratfemoralandtibialbonemarrowwascollectedforseparationandprimarycultureofbonemarrowmesenchymalstemcells.Bonemarrowmesenchymalstemcellculturesweredividedinto5groups:controlgroup,non-activatedgroup,aswellaslow-,medium-,andhigh-doseLPSgroups.Inthecontrolgroup,bonemarrowmesenchymalstemcellswereculturedwithDulbecco’smodifiedEagle’smedium(DMEM)supplementedwithfetalbovineserum(volumefraction0.1).Inthenon-activatedgroup,bonemarrowmesenchymalstemcellswereincubatedwithnon-activatedBV2supernatant.Inthelow-,medium-,andhigh-doseLPSgroups,bonemarrowmesenchymalstemcellswereincubatedwithLPS(0.01,0.1and1μg/L,respectively)-activatedBV2supernatant.MAIN

  • 标签: 脂多糖活性 BV2 骨髓间叶干细胞 小胶质
  • 简介:Acutemyeloidleukemia(AML)ischaracterizedbytheaccumulationofcirculatingimmatureblaststhatexhibituncontrolledgrowth,lacktheabilitytoundergonormaldifferentiation,andhavedecreasedsensitivitytoapoptosis.Accumulatingevidenceshowsthebonemarrow(BM)nicheiscriticaltothemaintenanceandretentionofhematopoieticstemcells(HSC),includingleukemiastemcells(LSC),andanincreasingnumberofstudieshavedemonstratedthatcrosstalkbetweenLSCandthestromalcellsassociatedwiththisnichegreatlyinfluencesleukemiainitiation,progression,andresponsetotherapy.Undeniably,stromalcellsintheBMnicheprovideasanctuaryinwhichLSCcanacquireadrug-resistantphenotypeandtherebyevadechemotherapyinduceddeath.YinandYang,theancientChinesephilosophicalconcept,vividlyportraystheintricateanddynamicinteractionsbetweenLSCandtheBMniche.Infact,LSC-inducedmicroenvironmentalreprogrammingcontributessignificantlytoleukemogenesis.Thus,identifyingthecriticalsignalingpathwaysinvolvedintheseinteractionswillcontributetotargetoptimizationandcombinatorialdrugtreatmentstrategiestoovercomeacquireddrugresistanceandpreventrelapsefollowingtherapy.Inthisreview,wedescribesomeofthecriticalsignalingpathwaysmediatingBMniche-LSCinteraction,includingSDF1/CXCL12,Wnt/β-catenin,VCAM/VLA-4/NF-κB,CD44,andhypoxiaasanewly-recognizedphysicaldeterminantofresistance,andoutlinetherapeuticstrategiesforovercomingtheseresistancefactors.

  • 标签: 骨髓基质干细胞 白血病 急性 β-catenin 药物治疗 基质细胞