The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in

Stem cell niches are defined as the cellular and molecular microenvironments that regulate stem cell function together with stem cell autonomous mechanisms. This includes control of the balance between quiescence, self-renewal, and differentiation, as well as the engagement of specific programs in response to stress. In mammals, the best understood niche is that harboring bone marrow hematopoietic stem cells (HSCs). Recent studies have expanded the number of cell types contributing to the HSC niche. Perivascular mesenchymal stem cells and macrophages now join the previously identified sinusoidal endothelial cells, sympathetic nerve fibers, and cells of the osteoblastic lineage to form similar, but distinct, niches that harbor dormant and self-renewing HSCs during homeostasis and mediate stem cell mobilization in response to granulocyte colony-stimulating factor.     

骨髓间充质干细胞诱导成骨细胞模拟造血龛支持造血干/祖细胞增殖

目的探讨骨髓间充质干细胞(MSC)诱导的成骨细胞复合人源生物衍生骨,构建三维培养体系,观察模拟的造血龛(hematopietic niche)对脐血CD34 造血干／祖细胞(HSPC)增殖的支持作用。方法分选人骨髓MSC及胎儿颅骨成骨细胞,将培养3代的MSC定向诱导为成骨细胞,分别将①MSC、②颅骨成骨细胞、③MSC与成骨细胞混合物(比例为1:2)及④MSC诱导的成骨细胞作为饲养细胞复合在人源生物衍生骨上,构建三维培养体系,同时用相应的饲养细胞层构建对应的二维培养体系。免疫磁珠分选脐血CD34 细胞,接种于各培养体系,无外源性细胞因子条件下进行培养。显微镜下观察各饲养细胞与人源生物衍生骨复合情况,通过流式细胞术、半固体细胞集落培养观察比较各培养体系支持HSPC的增殖能力。结果倒置相差显微镜、扫描电子显微镜以及免疫荧光标记观察结果显示,已成功地将MSC、颅骨成骨细胞、MSC和成骨细胞混合物及MSC诱导的成骨细胞复合在人源生物衍生骨上,构建了造血干细胞三维培养体系。在无外源细胞因子作用下,脐血HSPC培养2周造血祖细胞集落(CFU-C)与长期培养起始细胞(LTC-IC)分析,三维培养体系各组(①～④)CFU-C明显多于相应二维培养体系各组(①681．00±44．43比438．20±64．24;②729．80±37．72比536．60±35．31;③697．80±54．09比464．80±41．53;④740．20±47．66比513．40±65．56),P<0．05,但三维培养体系各组间差异无统计学意义(P>0．05)。三维培养体系各组LTC-IC也明显高于相应二维培养体系(分别为①68．00±5．11比26．00±3．73;②93．00±6．12比38．60±4．93;③83．40±5．85比36．20±4．52;④126．00±11．89比59．40±4．25),P<0．05,且三维培养体系中MSC诱导的成骨细胞组(④)LTC-IC明显多于其他各组。脐血HSPC培养5周,二维培养体系中饲养细胞层已逐渐崩解、脱落、死亡;而三维培养体系中饲养细胞层生长情况较好。三维体系各组CFU-C集落分析显示,MSC诱导的成骨细胞组(④)与其他三组间差异有统计学意义(①112．00±14．21;②186．17±24．80;③126．67±11．52;④257．00±28．78),P<0．05。结论骨髓MSC诱导分化的成骨细胞复合人源生物衍生骨构建的三维培养体系,对于脐血HSPC体外培养具有类似体内造血龛的支持作用,成骨细胞对造血干／祖细胞生存、增殖具有重要的调控作用。     

骨髓间充质干细胞与急性皮肤放射损伤的修复

背景:皮肤放射性损伤难治愈易复发常成为临床上难以解决的问题.随着干细胞丁程与组织学工程的进展,骨髓间充质干细胞实际应用研究日益受到重视,特别是其多向分化的潜能,显示了在创伤修复领域诱人的应用前景.目的:观察骨髓间充质干细胞对皮肤局部急性放射损伤的修复作用.设计、时间及地点:随机分组设计,对比观察,于2008-06/08在苏州大学附属第二医院血液病实验室完成.材料:雄性昆明小鼠46只,体质量(25+2)g,其中40只用于建立皮肤局部Ⅲ度放射损伤模型.方法:随机选取40只小鼠以3.6%水合氯醛腹腔麻醉,以能量为4 MeV的电子线(1 Gy/min)照射小鼠臀部皮肤,面积为2.0 cm×1.5 cm,总吸收剂量为40 Gy,后将小鼠随机分为实验组和对照组,每组20只.实验组照射后即刻经尾静脉注射经CFDA SE标记的骨髓间充质干细胞注射液0.1 mL(浓度为2×1010 L-1),对照组注射等量生理盐水,剩余6只不做照射处理,仅经尾静脉注射等量骨髓间充质干细胞.主要观察指标:实验组与对照组小鼠创面损伤情况及照射后2,3周皮肤病理变化,免疫组织化学分析皮肤新生血管;观察不同时间骨髓间充质干细胞在实验组小鼠皮肤及其他组织的分布情况.结果:将骨髓间充质干细胞经尾静脉移植入实验组小鼠后,实验组皮肤创面愈合速度比对照组快4～6 d.实验组创面损伤面积较对照组小,病理表现中表皮、毛囊、皮脂腺及胶原纤维的损伤程度均较同时期的对照组小鼠轻.皮肤创面中的新生毛细血管数高于对照组.实验组骨髓间充质干细胞在皮肤及其他组织中广泛分布且数量明显高于未照射的小鼠.结论:骨髓间充质干细胞对局部皮肤放射损伤创面有明显有效的修复作用,其作用是在干细胞与创伤局部微环境相互作用下实现的.     

骨髓间充质干细胞移植对缺血再灌注损伤肾组织细胞增殖的影响

目的探讨外源性的骨髓间充质干细胞(mesenchymalstemcells,MSCs)对缺血再灌注肾损伤的肾组织细胞增殖的影响。方法取SD雄性大鼠胫、股骨骨髓,percoll密度梯度分离法分离骨髓MSCs。32只雌性SD大鼠复制缺血再灌注肾损伤的模型,随机分为两个组:移植组和对照组。移植组经下腔静脉移植骨髓MSCs,对照组给予等量生理盐水,分别于1天、2天、3天、4天处死大鼠,两组大鼠每天均经腹腔注射5-溴脱氧尿苷嘧啶(bromodeoxyuridine,BrdU)。留取肾组织采用免疫组织化学染色方法检测BrdU阳性细胞在肾组织内的分布情况。结果在缺血再灌注后的第二天,移植组和对照组都有表达BrdU阳性细胞,并随时间延长BrdU阳性细胞个数逐渐增多,但移植组BrdU阳性细胞明显高于对照组,两者有统计学意义(P值<0.05)。结论移植的外源性骨髓MSCs能够促进损伤肾脏的细胞增殖,参与肾损伤的修复。     

骨髓间充质干细胞移植对缺血再灌注损伤肾组织细胞增殖的影响

目的探讨外源性的骨髓间充质干细胞(mesenchymal stem cells,MSCs)对缺血再灌注肾损伤的肾组织细胞增殖的影响.方法取SD雄性大鼠胫、股骨骨髓,percoll密度梯度分离法分离骨髓MSCs.32只雌性SD大鼠复制缺血再灌注肾损伤的模型,随机分为两个组:移植组和对照组.移植组经下腔静脉移植骨髓MSCs,对照组给予等量生理盐水,分别于1天、2天、3天、4天处死大鼠,两组大鼠每天均经腹腔注射5-溴脱氧尿苷嘧啶(bromodeoxyuridine,BrdU).留取肾组织采用免疫组织化学染色方法检测BrdU阳性细胞在肾组织内的分布情况.结果在缺血再灌注后的第二天,移植组和对照组都有表达BrdU阳性细胞,并随时间延长BrdU阳性细胞个数逐渐增多,但移植组BrdU阳性细胞明显高于对照组,两者有统计学意义(P值＜0.05).结论移植的外源性骨髓MSCs能够促进损伤肾脏的细胞增殖,参与肾损伤的修复.     

P-Selectin coated microtube for enrichment of CD34+ hematopoietic stem and progenitor cells from human bone marrow

BACKGROUND: Enrichment and purification of hematopoietic stem and progenitor cells (HSPCs) is important in transplantation therapies for hematologic disorders and in basic stem cell research. Primitive CD34+ HSPCs have demonstrated stronger rolling adhesion on selectins than mature CD34- mononuclear cells (MNCs). We have exploited this differential rolling behavior to capture and purify HSPCs from bone marrow by perfusing MNCs through selectin-coated microtubes. METHODS: Bone marrow MNCs were perfused through the cell-capture microtubes coated with adhesion molecules. We washed the device lumen and visualized and estimated captured cells by video microscopy. Adherent cells were eluted by high shear, calcium-free buffer, and air embolism. We used immunofluorescence staining followed by flow cytometry to analyze CD34+ HSPCs. RESULTS: CD34+ HSPC purity of cells captured in adhesion molecule-coated devices was significantly higher than the fraction of CD34+ cells found in bone marrow MNCs [mean (SE) 2.5% (0.8%)]. P-selectin-coated surfaces yielded 16% to 20% CD34+ cell purity, whereas antibody-coated surfaces yielded 12% to 18%. Although CD34+ cell purity was comparable between selectin and antibody surfaces, the total number of CD34+ HSPCs captured was significantly higher in P-selectin devices (approximately 5.7 x 10(4) to 7.1 x 10(4)) than antibody devices (approximately 1.74 x 10(4) to 2.61 x 10(4)). CONCLUSIONS: P-selectin can be used in a compact flow device to capture HSPCs. Selectin-mediated capture of CD34+ HSPCs resulted in enrichment approximately 8-fold higher than the CD34+ cell population from bone marrow MNCs. This study supports the hypothesis that flow-based, adhesion molecule-mediated capture may be a viable alternative approach to the capture and purification of HSPCs.     

骨髓间充质干细胞和心血管疾病

骨髓间充质干细胞(bone marrow mesenchymal stem cells,MSCs)能通过取代缺血坏死的心肌细胞,在损伤区域形成新生血管,修复损伤的细胞外基质,分泌各种细胞因子、细胞活素(旁分泌作用)等作用机制来治疗心血管疾病,MSCs将成为心血管疾病治疗最有前途的"种子"干细胞.     

Placenta perfusion has hematopoietic and mesenchymal progenitor stem cell potential

BACKGROUND: Placenta is a valuable source of stem cells for cell therapy and future application in the field of regenerative medicine. This is due to the plasticity and the immunomodulatory effects of the stem cells that it contains. In this study we present a totally closed method for hematopoietic and nonhematopoietic stem cell isolation from human term placenta. STUDY DESIGN AND METHODS: Sixty‐eight placenta units were collected and manipulated for the residual fetal blood drainage. After delivery, placenta flushing with citrate‐phosphate‐dextrose‐adenine was evaluated. RESULTS: Placenta flushing using a totally closed system led to a significant amount of hematopoietic progenitor cells and multipotent mesenchymal stem cells (MSCs) without additional microbial risk, free of maternal cell contamination. CONCLUSION: Traditionally discarded after childbirth, the term placenta now appears to be an easily accessible and abundant source of diverse origin stem cells suitable for banking strategies and for future clinical applications, including adult therapy.     

CD41+ and CD42+ hematopoietic progenitor cells may predict platelet engraftment after allogeneic peripheral blood stem cell transplantation

The objective of this study was to quantify subpopulations of CD34+ cells such as CD41+ and CD42+ cells that might represent megakaryocyte (MK) precursors in peripheral blood stem cell (PBSC) collections of normal, recombinant human granulocyte‐colony stimulating factor (rhG‐CSF) primed donors and to determine whether there is a statistical association between the dose infused megakaryocytic precursors and the time course of the platelet recovery following an allogeneic PBSC transplantation. Twenty‐six patients with various hematologic malignancies transplanted from their HLA identical siblings between July 1997 and December 1999 were used. All patients except one with severe aplastic anemia who had cyclophosphamide (CY) alone received busulfan‐CY as preparative regimen and cyclosporine‐methotrexate for GVHD prophylaxis. Normal healthy donors were given rhG‐CSF 10 μg/kg/day subcutaneously twice daily and PBSCs were collected on days 5 and 6. The median number of infused CD34+, CD41+ and CD42+ cells were 6.61 × 10⁶/kg (range 1.47–21.41), 54.85 × 10⁴/kg (5.38–204.19), and 49.86 × 10⁴/kg (6.82–430.10), respectively. Median days of ANC 0.5 × 10⁹/L and platelet 20 × 10⁹/L were 11.5 (range 9–15) and 13 (8–33), respectively. In this study, the number of CD41+ and CD42+ cells infused much better correlated than the number of CD34+ cells infused with the time to platelet recovery of 20 × 10⁹/L in 26 patients receiving an allogeneic match sibling PBSC transplantation (r = ?0.727 and P < 0.001 for CD41+ cells, r = ?0.806 and P < 0.001 for CD42+ cells, r = ?0.336 and P > 0.05 for CD34+ cells). There was an inverse correlation between the number of infused CD41+ and CD42+ cells and duration of platelet engraftment. Therefore, as the number of CD41+ and CD42+ cells increased, duration of platelet engraftment (time to reach platelet count of ≥ 20 × 10⁹/L) shortened significantly. Based on this data we may conclude that flow cytometric measurement of CD41+ and CD42+ progenitor cells may provide an accurate indication of platelet reconstitutive capacity of the allogeneic PBSC transplant. J. Clin. Apheresis. 16:67–73, 2001. © 2001 Wiley‐Liss, Inc.     

Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells

Pluripotent stem cells (PSCs) represent an alternative hematopoietic stem cell (HSC) source for treating hematopoietic disease. The limited engraftment of human PSC–derived (hPSC-derived) multipotent progenitor cells (MPP) has hampered the clinical application of these cells and suggests that MPP require additional cues for definitive hematopoiesis. We hypothesized that the presence of a vascular niche that produces Notch ligands jagged-1 (JAG1) and delta-like ligand-4 (DLL4) drives definitive hematopoiesis. We differentiated hes2 human embryonic stem cells (hESC) and Macaca nemestrina–induced PSC (iPSC) line-7 with cytokines in the presence or absence of endothelial cells (ECs) that express JAG1 and DLL4. Cells cocultured with ECs generated substantially more CD34⁺CD45⁺ hematopoietic progenitors compared with cells cocultured without ECs or with ECs lacking JAG1 or DLL4. EC-induced cells exhibited Notch activation and expressed HSC-specific Notch targets RUNX1 and GATA2. EC-induced PSC-MPP engrafted at a markedly higher level in NOD/SCID/IL-2 receptor γ chain–null (NSG) mice compared with cytokine-induced cells, and low-dose chemotherapy-based selection further increased engraftment. Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction were similar to levels achieved for cord blood–derived MPP and up to 20-fold higher than those achieved with hPSC-derived MPP engraftment. Our findings indicate that endothelial Notch ligands promote PSC-definitive hematopoiesis and production of long-term engrafting CD34⁺ cells, suggesting these ligands are critical for HSC emergence.     

骨髓间充质干细胞在骨组织工程中的应用

目的：综述具有向多种细胞分化潜能的骨髓间充质干细胞的生物学特性、分离纯化与培养技术、向骨和软骨定向诱导分化技术、细胞载体支架及其应用于骨组织工程的实验研究。 资料来源：应用计算机检索Medline数据库1990—01／2004-12期间的相关文章，检索词“mesenchymal stem cell，tissue engineer”，限定文章语言种类为英文。同时计算机检索中国期刊全文数据库、万方数据库1994—01／2004—12期间的相关文章，检索词”间充质干细胞、组织工程”，限定文章语言种类为中文。 资料选择：对资料进行初审，选取间充质干细胞特性、分离培养技术和其应用于组织工程的文献，重复研究选取代表性的、年代相对较近的文献作为纳入标准；然后筛除非骨组织工程的研究和重复研究，对剩余的文献开始查找全文。 资料提炼：共收集到78篇关于间充质干细胞应用于组织工程方面的文章，纳入31篇；排除47篇，13篇为重复研究，34篇为非骨组织工程研究。 资料综合：间充质干细胞主要存在于骨髓中，能向多种组织细胞分化，在体外可大量扩增。①间充质于细胞的分离纯化和培养目前主要有3种方法：密度梯度离心法、流式细胞仪分离法、贴壁筛选法。也有学者采用单细胞克隆技术获得纯化的间充质干细胞细胞株，但此种方法不便于大量获得种子细胞，目前应用较广泛的是密度梯度离心技术。②间充质干细胞在适宜的培养基中加入诱导剂可向骨、软骨细胞分化，其理想的载体支架应能均匀地搭载并保留细胞，支持血管快速内生，能透X射线利于观察新骨形成，新骨形成后能被吸收和替代以利骨改建，能容许或提高宿主骨的骨传导性桥接，表面与细胞相互作用以保留分化细胞的功能，组织相容性好。③间充质干细胞是理想的基因治疗的靶细胞，它可以转入生长因子和细胞因子基因，经多次分裂后体外仍表达外源蛋白。它应用于骨组织工程的动物试验中已获得了成功。 结论：以干细胞工程为代表的现代组织工程学近年来发展迅猛，但间充质干细胞组织工程学尚处于起步阶段。骨髓间充质干细胞具有易于取材、多组织分化潜能、遗传背景稳定、植入体内无排斥反应、高增殖的特性，决定了其将会成为细胞、基因治疗以及组织工程中十分有用的工具：     

骨髓间充质干细胞在骨组织工程中的应用

目的:综述具有向多种细胞分化潜能的骨髓间充质干细胞的生物学特性、分离纯化与培养技术、向骨和软骨定向诱导分化技术、细胞载体支架及其应用于骨组织工程的实验研究。资料来源:应用计算机检索Medline数据库1990-01/2004-12期间的相关文章,检索词“mesenchymalstemcell,tissueengineer”,限定文章语言种类为英文。同时计算机检索中国期刊全文数据库、万方数据库1994-01/2004-12期间的相关文章,检索词″间充质干细胞、组织工程″,限定文章语言种类为中文。资料选择:对资料进行初审,选取间充质干细胞特性、分离培养技术和其应用于组织工程的文献,重复研究选取代表性的、年代相对较近的文献作为纳入标准;然后筛除非骨组织工程的研究和重复研究,对剩余的文献开始查找全文。资料提炼:共收集到78篇关于间充质干细胞应用于组织工程方面的文章,纳入31篇;排除47篇,13篇为重复研究,34篇为非骨组织工程研究。资料综合:间充质干细胞主要存在于骨髓中,能向多种组织细胞分化,在体外可大量扩增。①间充质干细胞的分离纯化和培养目前主要有3种方法:密度梯度离心法、流式细胞仪分离法、贴壁筛选法。也有学者采用单细胞克隆技术获得纯化的间充质干细胞细胞株,但此种方法不便于大量获得种子细胞,目前应用较广泛的是密度梯度离心技术。②间充质干细胞在适宜的培养基中加入诱导剂可向骨、软骨细胞分化,其理想的载体支架应能均匀地搭载并保留细胞,支持血管快速内生,能透X射线利于观察新骨形成,新骨形成后能被吸收和替代以利骨改建,能容许或提高宿主骨的骨传导性桥接,表面与细胞相互作用以保留分化细胞的功能,组织相容性好。③间充质干细胞是理想的基因治疗的靶细胞,它可以转入生长因子和细胞因子基因,经多次分裂后体外仍表达外源蛋白。它应用于骨组织工程的动物试验中已获得了成功。结论:以干细胞工程为代表的现代组织工程学近年来发展迅猛,但间充质干细胞组织工程学尚处于起步阶段。骨髓间充质干细胞具有易于取材、多组织分化潜能、遗传背景稳定、植入体内无排斥反应、高增殖的特性,决定了其将会成为细胞、基因治疗以及组织工程中十分有用的工具。     

骨髓间充质干细胞与运动性膝关节损伤

背景:膝关节损伤是运动损伤中最常见的创伤之一,严重影响了运动员的训练和比赛,其损伤还可造成心血管和代谢的运动适应性减退和失用性肌萎缩.骨髓间充质干细胞以其多向分化潜能、低免疫原性、无排斥反应等优点为其在膝关节损伤的防治领域提供了广阔的应用前景.目的:总结骨髓间充质干细胞作用于运动性膝关节损伤的应用,旨在为膝关节损伤的预防和治疗提供科学依据.方法:通过计算机检索PubMed数据库检索1994-01/2010-05的文献资料,以"骨髓间充质干细胞、运动、膝关节损伤"为中文检索词,以"mesenchymal stem cell,spots,knee injuries"为英文检索词.纳入骨髓间充质干细胞和运动性膝关节损伤相关文献,排除重复性研究,共选取了34篇论文进行分析讨论.结果与结论:通过对骨髓间充质干细胞的生理特性、临床应用以及运动性膝关节损伤的因为分析,探讨骨髓间充质干细胞对运动性膝关节软骨、肌腱、肌细胞和半月板损伤的修复作用.结果发现骨髓间充质干细胞以其取材方便、创伤小且易于从骨髓中分离等的优点为修复膝关节软骨损伤、促进其肌腱的修复和治疗膝关节半月板损伤等有极为重要的价值.     

骨髓间充质干细胞移植治疗脑梗死的相关研究

学术背景:目前已有将骨髓间质干细胞用于脑梗死动物模型治疗的报道,国内外有关骨髓间质干细胞用于治疗脑梗死的研究也取得了一些进展,但是对于其作用机制还不清楚,国内外有关这方面的争论比较多。目的:就骨髓间质干细胞治疗脑梗死的研究进展及其治疗作用机制进行综述。检索策略:由第一、三作者应用计算机检索PUBMED 2000-07/2007-03期间与骨髓间充质干细胞和脑梗死有关的文章,检索词为"mesenchymal stem cells,cerebral ischemia,stroke"并限定文章语言种类为"English"。同时计算机检索中国期刊全文数据库2002-01/2007-03相关的文章,检索词为"骨髓间质干细胞,移植,脑梗死",并限定文章语言种类为中文。纳入标准:文章所述内容应与骨髓间质干细胞治疗脑梗死的应用研究及其治疗作用机制研究相关。排除标准:重复研究。文献评价:共收集到300篇相关文献,排除248篇内容陈旧或重复的文献,52篇符合纳入标准,有51篇检索到全文,选用其中的33篇作为本文参考文献:16篇涉及骨髓间质干细胞移植治疗脑梗死的相关研究;8篇神经干细胞移植后的示踪标记相关研究文章;5篇脑血管疾病干细胞移植治疗现状相关文章。资料综合:骨髓间质干细胞具有多向分化潜能,在特定条件下可分化为具有神经元形态并表达神经元标记物的细胞,在脑内可与损伤的细胞融合,能分泌营养因子或者刺激损伤部位产生内源性因子,促进损伤组织的修复并减少细胞凋亡,已成为细胞移植治疗各种疾病的理想种子细胞。结论:骨髓间质干细胞对脑梗死具有较好的治疗作用,主要通过其移植后能够分泌大量营养因子从而发挥其神经保护作用和营养支持作用。     

骨髓间充质干细胞作为干细胞参与生物材料异位诱导成骨

背景:体内骨组织工程是在骨或非骨部位植入具有骨诱导活性的生物材料,利用机体作为生物反应器去构建组织工程骨,以修复骨缺损.骨移植物所具备的优良生物相容性和机械性能为骨移植开辟新的治疗途径.然而,其相关干细胞来源尚不清楚.目的:探索骨髓间充质干细胞作为干细胞是否参与生物材料的异位诱导成骨.方法:分离纯化雄性beagle犬的骨髓间充质干细胞.将培养至第3代骨髓间充质干细胞移植入雌性beagle犬体内,建立同种异体骨髓移植模型,同期将双相钙磷陶瓷植入受体犬竖脊肌内.6周后,获取骨构建物标本,利用原位荧光杂交技术对骨移植物Y染色体进行示踪.结果与结论:原位荧光杂交结果显示Y染色体在骨构建物中有荧光信号表达,表明骨髓间充质干细胞可通过血液循环途径募集到异位生物材料处,形成骨组织.结果提示骨髓间充质干细胞参与生物材料异位诱导成骨,是生物材料异位诱导成骨干细胞来源之一.     

骨髓间充质干细胞移植在肾脏疾病防治中的应用

目的:探讨骨髓间充质干细胞在肾脏疾病中的应用。方法:应用计算机检索中文科技期刊数据库1994-01/2007-06期间与骨髓间充质干细胞移植和肾脏疾病防治相关的文献,检索词"骨髓间充质干细胞、肾脏疾病",限定文章语言种类为中文。对资料进行初审,并查看每篇文献后的引文,文献所述内容应与骨髓间充质干细胞移植、难治性肾病、肾功能衰竭相关,且以近5年发表在较权威杂志者优先。排除重复性文章及Meta分析类文章。结果:①骨髓间充质干细胞具有多向分化潜能和可塑性,在特定的条件下可以向肾病大鼠肾脏的肾小球及间质细胞转化。骨髓间充质干细胞移植后可对肾功能等生化指标有明显改善作用。②同种异基因骨髓移植治疗IgA肾病患者后,清除了在系膜沉积的IgA分子。③在慢性马兜铃酸肾病中,骨髓造血干细胞特异标志物CD34~ 细胞减少,推测慢性马兜铃酸肾病发病机理可能与骨髓间充质干细胞受损相关。④骨髓间充质干细胞还可以重建损伤后的肾小球系膜,将骨髓移植后的小鼠制成肾小球肾炎模型,一周后观察发现有骨髓间充质干细胞向系膜细胞分化。结论:骨髓间充质干细胞可分化成为各种肾脏细胞,从而修复肾损伤,为未来解决肾小球损伤、肾小管坏死及其导致的急、慢性肾功能衰竭提供了一种新型的治疗方案。     

骨髓间充质干细胞在软骨缺损修复中的应用

学术背景:骨髓间充质干细胞由于其易于获取,并可以在体外短期内大量扩增,是目前最有希望应用于软骨组织工程的干细胞.目的:对骨髓问充质干细胞在软骨缺损修复中的应用状况进行综述.检索策略: 由该论文的研究人员应用计算机检索1982-10/2006-12Pubmed数据库与骨髓间充质干细胞修复软骨缺损相关文献,检索词"Marrow;Mesenchymal stem cells:cartilage defect",限定语言种类为English,同时检索1982-10/2006-12中国科技成果数据库检索词"骨髓;间充质干细胞;软骨缺损",并限定文章语言种类为中文.共检索到126篇文献,对资料进行初审,纳入标准:①综述类及实验类文章;②中文核心期刊收录文献.排除标准:重复性研究.文献评价:文献的来源主要来自Pubmed数据库及中国科技成果数据库.文献类型为综述类及实验研究.资料综合:骨髓间充质干细胞在体内具有分化产生软骨的能力已被证明,而在体外培养条件下软骨表型的分化却是一个受多种因素限制的复杂过程,目前调控机制仍不明确.动物实验表明,骨髓间充质干细胞能够修复具有临床意义的骨和软骨缺损.虽然近年来对骨髓间充质干细胞及其在软骨组织工程方面的研究已取得较大进展,但对骨髓间充质干细胞分化各阶段细胞标志物、骨髓间充质干细胞的增殖、分化的控制及基因转染技术及临床应用的评估结果都有待进一步研究.结论:动物实验表明,骨髓间充质干细胞能够修复具有临床意义的骨和软骨缺损,虽然近年来对骨髓间充质干细胞及其在软骨组织工程方面的研究已取得较大进展,但对骨髓间充质干细胞的基础和临床研究中仍存在诸多问题需要解决.     

Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow

Formation of the hematopoietic stem cell (HSC) niche in bone marrow (BM) is tightly associated with endochondral ossification, but little is known about the mechanisms involved. We used the oc/oc mouse, a mouse model with impaired endochondral ossification caused by a loss of osteoclast (OCL) activity, to investigate the role of osteoblasts (OBLs) and OCLs in the HSC niche formation. The absence of OCL activity resulted in a defective HSC niche associated with an increased proportion of mesenchymal progenitors but reduced osteoblastic differentiation, leading to impaired HSC homing to the BM. Restoration of OCL activity reversed the defect in HSC niche formation. Our data demonstrate that OBLs are required for establishing HSC niches and that osteoblastic development is induced by OCLs. These findings broaden our knowledge of the HSC niche formation, which is critical for understanding normal and pathological hematopoiesis.