Retrovirus-mediated gene transfer into human hematopoietic stem cells

 Human hematopoietic stem cells genetically modified by retroviral-mediated gene transfer may offer new treatment options for patients with genetic disease. The potential of gene-modified hematopoietic stem cells as vehicles for gene delivery was first illustrated by the demonstration that hematopoietic systems of lethally irradiated mice can be reconstituted with retroviral vector transduced syngeneic bone marrow, and that these cells can in turn provide genetically marked progeny which persist in blood and marrow over extended time periods [1–4]. In contrast, hematopoietic stem cells from large animals prove difficult to transduce with retroviral vectors and are consequently less likely to function as vehicles for long-term gene therapy. Indeed, clinically relevant levels of gene transfer into large animal and human hematopoietic stem cells has not been widely achieved. The need for improved retroviral vector systems and for understanding the biology of hematopoietic stem cell gene transfer continue to fuel intense research activity. Preliminary results from human stem cell gene marking and gene therapy trials currently underway are encouraging. This contribution reviews the underlying concepts relevant to retroviral-mediated gene transfer into hematopoietic stem cells. We survey the evolution of approaches for gene transfer into hematopoietic stem cells, from murine and large animal models to the first human clinical trials. Finally, we discuss new strategies which are currently being pursued. Received: 12 March 1997 / Accepted: 21 July 1997     

人胚胎干细胞HuES17向造血干细胞的分化

背景：人类胚胎干细胞是来源于着床前囊胚的内细胞团,能在长期培养中无限增殖并保持未分化状态,且具有分化成人体组织各种细胞类型能力的细胞。 目的：进一步验证人胚胎干细胞HuES17细胞株向造血干细胞分化的能力。 方法：人胚胎干细胞HuES17采用与人包皮成纤维细胞二维共培养的方式培养,采用人胚胎干细胞与小鼠骨髓基质细胞(OP9) 二维共培养的方法诱导胚胎干细胞向造血干细胞分化。 结果与结论：人胚胎干细胞与小鼠骨髓基质细胞(OP9) 二维共培养诱导造血分化的第四五天即开始出现OP9细胞逐渐老化,很快死亡;可以观察到人胚胎干细胞分化,然而,随着OP9细胞死亡,分化的人胚胎干细胞亦死亡,不能诱导人胚胎干细胞向造血干细胞分化。提示人胚胎干细胞HuES17细胞株可能不能向造血干细胞分化,或向造血干细胞分化的能力较低。     

Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes

Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T- and B-cell function and, in some types, also of NK cells and function. Mutations in thirteen different genes have been found to cause this condition, which is uniformly fatal in the first 2?years of life unless immune reconstitution can be accomplished. In the 42?years since the first bone marrow transplant was given in 1968, the standard treatment for all forms of SCID has been allogeneic bone marrow transplantation. Both HLA-identical unfractionated and T-cell-depleted HLA-haploidentical bone marrow transplants have been very successful in effecting immune reconstitution, especially if performed in the first 3.5?months of life and without pre-transplant chemotherapy. This paper summarizes the longterm outcome, according to molecular type, of 166 consecutive SCID infants given non-conditioned related donor bone marrow transplants at this institution over the past 28.3?years and reviews published reports of longterm outcomes of transplants in SCID performed at other centers.     

人主动脉-性腺-中肾区基质细胞诱导胚胎干细胞分化为造血干细胞及体内造血重建

背景：研究证实多种造血生长因子、基质细胞饲养层及其条件培养液可促进胚胎干细胞向造血干细胞分化。 目的：以人主动脉-性腺-中肾(aorta-gonad-mesonephros,AGM)区基质细胞为饲养层体外诱导小鼠胚胎干细胞分化为造血干细胞,并比较不同移植途径对造血干细胞体内造血重建能力的影响。 方法：将小鼠E14 胚胎干细胞诱导为拟胚体,采用Transwell非接触共培养体系在人AGM区基质细胞饲养层上诱导6 d,接种NOD-SCID小鼠检测体内致瘤性。再将诱导后的拟胚体细胞移植经致死量60Co γ射线辐照的BALB/C雌鼠,受鼠随机分为静脉移植组、骨髓腔移植组、照射对照组及正常对照组。 结果与结论：拟胚体细胞经人AGM区基质细胞诱导后Sca-1⁺c-Kit⁺细胞占(13.12±1.30)%。NOD-SCID小鼠皮下接种经人AGM区基质细胞诱导的拟胚体细胞可出现畸胎瘤,经骨髓腔接种未见肿瘤形成。静脉移植组动物全部死亡,骨髓腔移植组生存率为55.6%,移植后21 d外周血象基本恢复,存活受鼠检测到供体来源Sry基因。提示小鼠胚胎干细胞经人AGM区基质细胞诱导分化的造血干细胞通过骨髓腔移植安全并具有一定的造血重建能力。     

胚胎干细胞移植治疗急性心肌梗死后心肌病理形态学及血流动力学变化

目的：探讨胚胎干细胞(ESC)移植治疗急性心肌梗死(AMI)后心肌组织形态学及血液动力学变化。 方法： Wistar大鼠40只随机分为正常对照组、梗死未治疗组(梗死组)、梗死中心移植组(中心组)、梗死周边移植组(周边组)共4组。结扎冠状动脉左前降支制成心肌梗死模型，梗死后1周移植体外分化并经标记的ESCs，移植后4周分别检测组织形态及血流动力学指标的改变。 结果： 移植后4周，周边组移植细胞稳定存活，而中心组移植细胞未能存活。心功能及组织学检测表明中心组与梗死组无显著差异(P＞0.05)；与梗死组比较，周边组梗死面积显著小于梗死组(P＜0.01)，(21.0±1.3)% vs (40.7±2.2)%；左室重量小于梗死组(P＜0.01)，(702.0±24.0)mg vs (882.2±32.6)mg；反映左室收缩功能的指标+dp/dtmax和LVSP均大于梗死组(P＜0.01)，分别为 (7.9±0.7)×103mmHg/s vs (5.9±0.5)×103 mmHg/s和(117.5±10.7) mmHg vs (89.2±8.1) mmHg；而LVEDP均明显小于梗死组(P＜0.01)，(8.5±0.3)mmHg vs (13.6±1.2)mmHg。 结论： 急性心肌梗死后于梗死周边区移植ESCs可以阻止心室重构、减少瘢痕面积、改善心功能。     

Transplantation of human undifferentiated embryonic stem cells into a myocardial infarction rat model

Human embryonic stem (hES) cells hold great therapeutic potential for cell transplantation. To date, it remains uncertain whether undifferentiated hES cells can differentiate into cardiac lineage in vivo during myocardial infarction. Here we provide the first report that undifferentiated hES cells can survive in rat hearts during myocardial infarction without the formation of teratoma using undifferentiated green fluorescent protein (GFP)-transgenic hES cells. Using a laser-capture microscope to dissect the GFP-positive cell area from the hES-injected hearts, we documented the expression of human cardiac-specific genes, including GATA-4, Nkx-2.5, and cardiac troponin I. Taken together, our results demonstrate that undifferentiated hES cells can be driven to the cardiac lineage under the local injured environment in the heart, which may provide a potential method for regenerating de novo myocardium to treat myocardial infarction.     

Lentil lectin inhibits cells producing graft-versus-host reaction but does not suppress hematopoietic stem cells in mice

Treatment of mouse donors or recipients of allogeneic spleen cells with repeated injections of lentil lectin markedly suppressed regional and systemic graft-versus-host reactions. The lectin acted selectively on lymphoid cells; hematopoietic stem cells were largely left unaffected. Repeated administration of the lectin decreased the number of lymphocytes and red blood cells and the amount of hemoglobin; other white blood cells increased in number.     

造血干细胞移植治疗地中海贫血

背景：造血干细胞移植是目前根治地中海贫血的最佳方法,造血干细胞移植包括骨髓移植、脐血移植、宫内造血干细胞移植、外周血造血干细胞移植。 目的：利用SCI数据库文献检索和深度分析功能,对造血干细胞移植的研究文献进行多层次探讨分析。 方法：以“造血干细胞(hematopoietic stem cell or HSC);移植(transplantation);地中海贫血(thalassaemia or thalassemia);β型地中海贫血(beta thalassaemia or beta thalassemia or β thalassaemia or β thalassemia)”为关键词,检索SCI数据库2002-01/2011-12的相关文献,并将分析结果及资料导出,以文字和图表的形式进行统计和计量分析,描述其分布特征。纳入标准：检索与造血干细胞移植治疗地中海贫血相关的文献。文献类型包括：①研究原著。②会议摘要。③综述。④会议文章。⑤快报。⑥编辑素材。⑦勘误。⑧章节。⑨新闻。排除标准：①与文章目的无关的文献。②大于10年较陈旧的文献。③未发表的文章。 结果与结论：SCI数据库2002/2011共检索到8 981篇造血干细胞移植相关的文献,研究原著以4 922篇位居首位,其中有7篇可以确定为经典文献,文献数量在2002/2011呈总体上升趋势,Blood《血液》杂志发表文献量最多, 1 515篇,占全部文献的16.87%。通过文献计量学方法对来源于SCI数据库关于造血干细胞移植的文献进行分析,可为了解该领域的现状、趋势和研究者进一步确定热点难点提供有价值的参考。     

Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.     

Notch1 but not Notch2 is essential for generating hematopoietic stem cells from endothelial cells

Hematopoietic stem cells (HSCs) are thought to arise in the aorta-gonad-mesonephros (AGM) region of embryo proper, although HSC activity can be detected in yolk sac (YS) and paraaortic splanchnopleura (P-Sp) when transplanted in newborn mice. We examined the role of Notch signaling in embryonic hematopoiesis. The activity of colony-forming cells in the YS from Notch1(-/-) embryos was comparable to that of wild-type embryos. However, in vitro and in vivo definitive hematopoietic activities from YS and P-Sp were severely impaired in Notch1(-/-) embryos. The population representing hemogenic endothelial cells, however, did not decrease. In contrast, Notch2(-/-) embryos showed no hematopoietic deficiency. These data indicate that Notch1, but not Notch2, is essential for generating hematopoietic stem cells from endothelial cells.     

Hypoxic metabolism in human hematopoietic stem cells

<正>AIM:To unravel the metabolic phenotype of human hematopoietic progenitor and stem cells(HPSCs).METHODS:Flow cytometric profiling and separation of human MPB cells based on their mitochondrial activity were performed using MitoT racker dyes and used for further analysis of metabolic profiles and underlying mechanisms.RESULTS:We showed that HPSCs had a similar metabolic     

人AGM区及胎肝基质细胞促进小鼠胚胎干细胞向造血干细胞分化和体内造血重建

目的: 探讨小鼠胚胎干细胞(ESCs)经人主动脉-性腺-中肾(AGM)区及胎肝(FL)基质细胞程序诱导后,向造血干细胞(HSCs)分化的效率及其造血功能。方法: 将E14 ESCs诱导为拟胚体(EB),并在人AGM区及FL基质细胞饲养层上进一步诱导分化,培养6 d后收集细胞检测Sca-1⁺c-Kit⁺细胞含量、分析造血细胞集落形成能力及致瘤性。再将不同诱导阶段的EB来源细胞移植经致死量 γ射线辐照的BALB/c雌鼠,观察生存率、植入状况和造血重建。结果: (1)EB来源细胞经人AGM区及FL基质细胞程序诱导后Sca-1⁺c-Kit⁺细胞含量为(21.96±2.54)%,造血集落总数为(520±52)/10⁵cells,明显优于诱导前及人AGM区基质细胞初步诱导者(P＜0.05)。(2)NOD-SCID小鼠接种经人AGM区及FL基质细胞诱导的ESCs未见畸胎瘤。(3)BALB/c雌鼠移植经人AGM区及FL基质细胞诱导的EB来源细胞后生存率77.8%,14 d外周血细胞计数明显改善,存活受鼠均检测到供体来源sry基因,而移植人AGM区基质细胞诱导的EB细胞者15 d内全部死亡。结论: 人AGM区及FL基质细胞能促进小鼠ESCs定向分化为HSCs,有效重建体内造血功能。     

含人AGM区基质细胞培养体系定向诱导胚胎干细胞为造血干细胞的实验研究

目的： 体外模拟胚胎早期AGM区造血微环境，诱导胚胎干细胞（ESCs）分化为造血干细胞（HSCs）。方法：将小鼠E14 ESCs在含BMP-4及VEGF的半固体培养基中诱导为拟胚体（EB），分别于3、6、9、12、15 d时收获EB，流式细胞术检测Flk-1+细胞含量。取Flk-1+ 细胞处于高峰期的EB细胞，在人AGM区基质细胞饲养层上进一步诱导分化，并设无饲养层对照，分别于3、6、9、12 d时收获细胞计数、流式细胞术检测Sca-1+c-kit+ 细胞含量，并分析造血细胞集落形成能力。结果：诱导E14细胞形成EB过程中添加BMP4+VEGF的因子组Flk-1+细胞在第9 d达峰值（27.53%± 2.84％），与未添加因子组（8.77%± 1.12％）比较差异显著(P<0.05)。将培养9 d的EB细胞在hAGMS3、hAGMS4饲养层上进一步诱导分化，第6 d时Sca-1+c-kit+细胞达峰值，分别为7.31%±1.21％、7.62%±1.52％，其绝对数分别扩增(2.57±0.48)倍、(2.35±0.36)倍，与无饲养层组比较显著差异（P<0.05）。该分化阶段的Sca-1+c-kit+细胞具有形成各系造血细胞集落的能力。结论：人胚早期AGM区基质细胞能促进小鼠ESCs定向分化为HSCs，为研究ESCs分化为HSCs的分子机制提供了实验模型。     

人骨髓间质干细胞向造血细胞分化潜能的实验研究

目的:在体研究人骨髓间质干细胞(hBMMSCs)向造血细胞分化的潜能。方法:将hBMMSCs经尾静脉注射给环磷酰胺处理的严重联合免疫缺陷(SCID)小鼠,利用流式激活细胞分析系统(FACS)检测hBMMSCs输注后存活35d的SCID小鼠外周血、骨髓和脾脏中人源性造血细胞的表型和水平。结果:hBMMSCs输注组外周血(PB)、骨髓(BM)和脾脏(spleen)中可检测到人CD45⁺/H-2D^d-、CD34⁺/H-2D^d-细胞,而对照组PB、BM和脾脏均未检测到上述表型的人造血细胞。结论:hBMMSCs具有向造血细胞分化的潜能。     

Adipocyte differentiation of human marrow mesenchymal stem cells reduces the supporting capacity for hematopoietic progenitors but not for severe combined immunodeficiency repopulating cells

Bone marrow stromal cells provide a microenvironment for hematopoiesis. Adipocytes are the major stromal cell phenotype in bone marrow, but their function in hematopoiesis is poorly understood. In this study, we compared the hematopoietic-supporting capacity of adipocytes and their progenitor, mesenchymal stem cells (MSCs), by culturing human cord blood (CB) CD34+CD38- hematopoietic progenitor cells (HPCs) on a layer of adipocytes or MSCs. CB CD34+CD38- cells cultured on MSCs generated higher proportions of CD34+CD38- HPCs and colony-forming cells than those cultures on a layer of adipocytes, indicating an inferior hematopoietic support by adipocytes. However, CB CD34+CD38- HPCs cultured on MSCs and adipocytes were equally capable of reconstituting human hematopoiesis in non-obese diabetic/severe combined immunodeficient disease (NOD/SCID) mice. These findings show that differentiation of MSCs into adipocytes is accompanied by the loss of capacity to support mature HPCs, but not transplantable SCID-repopulating cells.     

Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung

Murine mesenchymal stem cells are capable of differentiation into multiple cell types both in vitro and in vivo and may be good candidates to use as cell therapy for diseased or damaged organs. We have previously reported a method of enriching a population of murine MSCs that demonstrated a diverse differentiation potential both in vitro and in vivo. In this study, we show that this enriched population of murine mesenchymal stem cells embolize within lung capillaries following systemic injection and then rapidly expand within, and invade into, the lung parenchyma, forming tumor nodules. These lesions rarely contain cells bearing the immunohistochemical characteristics of lung epithelium, but they do show the characteristics of immature bone and cartilage that resembles exuberant fracture callus or well-differentiated osteosarcoma. Our findings indicate that murine mesenchymal stem cells can behave in a manner similar to tumor cells, with dysregulated growth and aberrant differentiation within the alveolar microenvironment after four passages. We demonstrate that unlike human MSCs, MSCs from different mouse strains can acquire chromosomal abnormalities after only a few in vitro passages. Moreover, other parameters, such as mouse strain used, might also play a role in the induction of these tumors. These findings might be clinically relevant for future stem cell therapy studies. Disclosure of potential conflicts of interest is found at the end of this article.     

The role of apoptosis in regulating hematopoiesis and hematopoietic stem cells

Apoptosis, or the ability of cells to die in an orderly and highly regulated manner, is essential for normal development and homeostasis of multicellular organisms. Diseases in which deregulation of this process is implicated include autoimmune diseases, cancer and Alzheimer's disease. The importance of apoptosis for the development and function of lymphoid cells has been extensively investigated. Less clear is the role apoptosis plays in regulating early progenitor and stem cell compartments. This question is being investigated using, a transgenic mouse model, H2K-BCL-2, in which all hematopoietic cells have an increased resistance to apoptosis. The same transgenic model is also being used to address the question whether protection against apoptosisc an increase system-wide resistance to lethal challenges such as irradiation and chemotherapeutic agents.     

人脐血间充质干细胞移植修复骨髓造血损伤

文题释义：间充质干细胞：是一种多功能干细胞,由胚胎发育早期的中胚层发展而来,存在于人的各种组织、器官中,如骨、软骨、脂肪、外周血和肌肉等。骨髓组织中的间充质干细胞最多,但其在骨髓细胞中的比例仍很低,只有0.01%-1.00%,且年龄越大其含量越少,骨髓中的间充质干细胞分化能力也呈下降趋势。与骨髓相比,脐血中所含的间充质干细胞更加原始,因而有更强的增殖、分化能力。相较于骨髓间充质干细胞而言,人脐血间充质干细胞具有来源广泛、取材方便、无伦理方面的限制,使得人脐血间充质干细胞成为再生医学中的另一重要来源。骨髓造血损伤动物模型：建立骨髓造血损伤动物模型的方法有很多,主要分为物理方法、化学方法及物理化学方法等。物理方法包括各种射线,如X射线等,化学方法主要指以环磷酰胺为代表的烷化剂类化疗药物,而物理化学方法也叫混合性方法,联合应用放射线和化疗药物建立动物模型。  摘要背景：大多数研究间充质干细胞体外培养对造血干细胞的增殖作用和骨髓间充质干细胞移植可降低辐照引起的造血细胞死亡,增加骨髓细胞存活,修复造血功能,而少有研究人脐血间充质干细胞移植对骨髓造血损伤的修复。目的：探讨人脐血间充质干细胞对骨髓造血微环境的修复情况。方法：选用雄性BALB/c小鼠随机分为3组,实验组和对照组小鼠进行总剂量为6 Gy的X射线全身照射,建立骨髓造血损伤模型,正常组为未经处理的正常小鼠。实验组小鼠照射当天经尾静脉输入CM-DiL标记的人脐血间充质干细胞5×10⁶/只(0.2 mL),对照组和正常组经尾静脉输入生理盐水0.2 mL,移植后第1,5,7,14,21天观察外周血血象恢复情况和骨髓造血微环境修复情况。结果与结论：①外周血常规：移植后第1,5,7天,实验组和对照组小鼠与正常组小鼠比较,白细胞、血小板、红细胞计数及血红蛋白浓度进行性下降,第7天下降最为明显,移植后第14天三系较前有所恢复,移植后第21天基本恢复正常,与实验组相比,对照组三系下降更为明显,移植后第14天实验组较对照组恢复快;②骨髓涂片情况：移植后第1,5,7,14天实验组及对照组小鼠骨髓出现造血功能抑制,以第7天最为明显,移植后第14天骨髓增生较前有所恢复,实验组优于对照组;移植后第21天实验组及对照组小鼠骨髓造血功能恢复,与正常组相比无差异;③骨髓病理切片情况：移植后第1,5,7,14天实验组及对照组小鼠骨髓出现造血功能抑制;移植后第14天实验组及对照组小鼠的骨髓造血功能较前开始恢复,实验组小鼠的骨髓增生情况优于对照组小鼠, 移植后第21天实验组及对照组小鼠骨髓增生情况与正常组比较无差异;④结果表明,人脐血间充质干细胞对骨髓造血功能恢复均有明显促进作用。ORCID: 0000-0002-7547-9664(高坤莉) 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

胚胎干细胞源性神经前体细胞移植脑缺血大鼠局部细胞的免疫反应

背景：神经前体细胞的免疫原性各家研究结果不一,尤其是体内移植后的机体免疫反应模式需要进一步研究。 目的：体外观察神经前体细胞组成型及诱导型主要组织相容性抗原表达情况;体内观察神经前体细胞移植入大鼠脑缺血组织后局部免疫细胞活化情况,探讨神经前体细胞的移植排斥可能性及模式。 方法：自pCX-hrGFP ES-D3胚胎干细胞诱导分化神经前体细胞,流式细胞术体外检测主要组织相容性抗原Ⅰ,Ⅱ类分子表达及γ-干扰素诱导前后表达变化。实验分3组,磷酸盐缓冲液组、神经前体细胞组分别于大脑中动脉缺血大鼠模型造模后经侧脑室给予磷酸盐缓冲液注射及神经前体细胞移植,假手术组不造模。免疫组化法观察纹状区ED1+、CD4+、CD8+细胞浸润情况;淋巴细胞再刺激增殖实验观测神经前体细胞诱导移植大鼠颈部淋巴细胞的增殖指数。 结果与结论：神经前体细胞组成型高表达主要组织相容性抗原Ⅰ类分子,几乎不表达主要组织相容性抗原Ⅱ类分子;经γ-干扰素诱导后,主要组织相容性抗原Ⅰ类分子进一步上调,主要组织相容性抗原Ⅱ类分子亦有轻度上调,提示神经前体细胞有可能引起机体免疫反应。移植实验表明,与假手术组相比,磷酸盐缓冲液组及神经前体细胞组均表现强烈的ED1+、CD4+、CD8+细胞浸润(P < 0.05),说明脑缺血损伤本身能导致局部免疫细胞活化;神经前体细胞组比磷酸盐缓冲液组有更强的ED1+、CD4+细胞浸润(P < 0.05),提示神经前体细胞移植可能导致局部免疫更进一步活化,且以CD4+T细胞反应为主。磷酸盐缓冲液组及神经前体细胞组神经前体细胞诱导下的增殖指数值均较假手术组升高(P < 0.01),但前两组增殖指数值比较差异无显著性意义(P > 0.05),提示脑组织局部炎症导致颈部淋巴细胞增殖性增加,而离体神经前体细胞不足以单独刺激致敏淋巴细胞增殖。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：