BACKGROUND & AIMS: A 38-year-old man, blood group A+, was allotransplanted for multiple myeloma from his fully matched sister, blood group O+. Anti-A antibodies IgG and IgM titres of the donor were low. Allogeneic peripheral blood stem cells were harvested by leukapheresis after subcutaneous administration of G-CSF. Rapid engraftment occurred since 5.6 x 10(9)/l leukocytes were achieved on day +9 post-transplant. At this time a severe immune haemolytic syndrome occurred and direct antiglobulin test was positive (IgG and C3d). Elution showed an anti-A specificity. Evolution was rapidly unfavourable related to multiorgan failure. The patient died on day +20 post-transplant.

背景与目标： 一名38岁的A血型男子从其完全匹配的姐姐O血型中同种异体移植了多发性骨髓瘤。供体的抗A抗体IgG和IgM滴度较低。皮下给予g-csf后，通过白细胞分离术收集异基因外周血干细胞。由于在移植后第9天实现了5.6 × 10(9)/l白细胞，因此发生了快速植入。此时发生了严重的免疫溶血综合征，直接抗球蛋白试验呈阳性 (IgG和C3d)。洗脱显示出抗A特异性。进化与多器官衰竭迅速不利。患者在移植后第20天死亡。

BACKGROUND & AIMS: :Human embryonic and mesenchymal stem cell therapies may offer significant benefit to a large number of patients. Recently, however, human embryonic stem cell lines cultured on mouse feeder cells were reported to be contaminated by the xeno-carbohydrate N-glycolylneuraminic acid (Neu5Gc) and considered potentially unfit for human therapy. To determine the extent of the problem of Neu5Gc contamination for the development of stem cell therapies, we investigated whether it also occurs in cells cultured on human feeder cells and in mesenchymal stem cells, what are the sources of contamination, and whether the contamination is reversible. We found that N-glycolylneuraminic acid was present in embryonic stem cells cultured on human feeder cells, correlating with the presence of Neu5Gc in components of the commercial serum replacement culture medium. Similar contamination occurred in mesenchymal stem cells cultured in the presence of fetal bovine serum. The results suggest that the Neu5Gc is present in both glycoprotein and lipid-linked glycans, as detected by mass spectrometric analysis and monoclonal antibody staining, respectively. Significantly, the contamination was largely reversible in the progeny of both cell types, suggesting that decontaminated cells may be derived from existing stem cell lines. Although major complications have not been reported in the clinical trials with mesenchymal stem cells exposed to fetal bovine serum, the immunogenic contamination may potentially be reflected in the viability and efficacy of the transplanted cells and thus bias the published results. Definition of safe culture conditions for stem cells is essential for future development of cellular therapies.

背景与目标： : 人类胚胎和间充质干细胞疗法可能为大量患者提供显着益处。然而，最近，据报道，在小鼠饲养细胞上培养的人类胚胎干细胞系被异种碳水化合物N-糖基神经氨酸 (Neu5Gc) 污染，并被认为可能不适合人类治疗。为了确定Neu5Gc污染在干细胞疗法发展中的问题程度，我们调查了它是否也发生在人类饲养细胞和间充质干细胞上培养的细胞中，什么是污染源，以及污染是否可逆。我们发现N-甘氨酰神经氨酸存在于在人饲养细胞上培养的胚胎干细胞中，这与商业血清替代培养基成分中Neu5Gc的存在有关。在胎牛血清存在下培养的间充质干细胞中也发生了类似的污染。结果表明，分别通过质谱分析和单克隆抗体染色检测到，Neu5Gc存在于糖蛋白和脂质连接的聚糖中。值得注意的是，在两种细胞类型的后代中，污染在很大程度上是可逆的，这表明去污的细胞可能来自现有的干细胞系。尽管在暴露于胎牛血清的间充质干细胞的临床试验中尚未报道主要并发症，但免疫原性污染可能反映在移植细胞的活力和功效中，从而使已发表的结果产生偏差。干细胞安全培养条件的定义对于细胞疗法的未来发展至关重要。

BACKGROUND & AIMS: Human parvovirus B19 (B19) IgG was studied retrospectively in 66 allogeneic bone marrow transplantation (BMT) patients using an enzyme-linked immunosorbent assay. Recipient and donor sera had been stored pre-BMT together with sequential sera thereafter. Approximately half of donors and recipients had anti-B19 IgG pre-BMT and thus the relative contributions of donor and recipient immunity to antibody production after transplantation could be assessed. For each patient, a serum taken 2 to 3 years after BMT was also tested and the results show that persistence of B19 antibody depends on prior recipient (P = .0003) but not on donor immunity (P = .8). The findings were similar in both sibling and (VUD) BMT volunteer unrelated donor patients. Analysis of sequential post-BMT sera from 41 of the patients, for whom appropriately timed samples were available, showed primary B19 infection in 3 seronegative individuals, whereas 5 others who were seropositive before BMT underwent recurrent infection. Sequential results from the remaining 33 patients without recent B19 infection showed no evidence for donor antibody transfer and confirmed that antibody persistence depends on prior recipient immunity. B19 IgG levels decreased variably with time and some patients eventually became seronegative. It is concluded that this long-term persistence of B19 antibody post-BMT is most probably due to the existence of long-lived recipient plasma cells.

背景与目标： 使用酶联免疫吸附测定法对66例同种异体骨髓移植 (BMT) 患者进行了人细小病毒B19 (B19) IgG的回顾性研究。受体和供体血清已在BMT之前与随后的连续血清一起存储。大约一半的供体和受体具有anti-B19的IgG pre-BMT，因此可以评估供体和受体免疫对移植后抗体产生的相对贡献。对于每个患者，还测试了BMT后2至3年的血清，结果表明B19抗体的持久性取决于先前的接受者 (P = .0003)，而不取决于供体免疫 (P = .8)。兄弟姐妹和 (VUD) BMT志愿无关的供体患者的发现相似。对41名患者的BMT后血清的顺序分析 (可提供适当的定时样本) 显示，3名血清阴性个体的原发性B19感染，而其他5名在BMT复发性感染之前血清呈阳性。其余33例近期未感染B19的患者的连续结果显示没有供体抗体转移的证据，并证实抗体的持久性取决于先前的受体免疫力。B19 IgG水平随时间变化而降低，一些患者最终出现血清阴性。结论是，B19抗体在BMT后的这种长期持久性很可能是由于存在长寿的受体浆细胞。

BACKGROUND & AIMS: :Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.

背景与目标： : 依那西普是一种重组人可溶性肿瘤坏死因子 (TNF-α) 受体融合蛋白，可抑制TNF-α，TNF-α 是移植物抗宿主病 (GVHD) 发病机理中的主要介质。我们研究的目的是评估依那西普治疗21例类固醇难治性急性GVHD (aGVHD) (n = 13) 和慢性GVHD (cGVHD) (n = 8) 患者的安全性和有效性。依那西普25 mg，每周皮下注射两次，持续4周，然后每周注射25 mg，持续4周。在开始使用依那西普时，14例患者有皮肤，13例有胃肠道，5例有肝脏，5例有肺部，4例有口腔受累。12名患者 (57%) 完成12剂治疗。总体而言，21例患者中有11例 (52%) 对依那西普治疗有反应，其中6例 (46% 例) aGVHD [n = 4完全缓解 (CR)，n = 2部分缓解 (PR)] 和5例 (62%) cGVHD (n = 1 CR，n = 4 PR)。临床反应最常见于难治性肠道aGVHD患者，其中55% 患者具有CR，9% 患者具有PR。48% 患者发生CMV再激活，14% 患者发生细菌感染，19% 患者发生真菌感染。自依那西普开始以来，中位随访429天 (范围71-1007天) 后，有14名患者 (67%) 还活着。7例患者死亡，3例感染，2例难治性aGVHD，2例疾病进展。总之，我们的初步数据表明，依那西普具有良好的耐受性，并且可以在类固醇难治性aGVHD和cGVHD患者中诱导高反应率，尤其是在GI受累的情况下。

BACKGROUND & AIMS: :There is an abundance of clinical applications using human umbilical cord blood (HUCB) as a source for stem cell populations. Other than haematopoietic progenitors, there are mesenchymal, endothelial stem cells and neuronal precursors, in varying quantities, that are found in human umbilical cord blood. These may be useful in diseases such as immune deficiency and autoimmune disorders. Considering issues of safety, availability, transplant methodology, rejection and side effects, it is contended that a therapeutic stem cell transplant, utilizing stem cells from HUCB, provides a reliable repository of early precursor cells that can be useful in a great number of diverse conditions. Drawbacks of relatively smaller quantities of mononucleated cells in one unit of cord blood can be mitigated by in-vitro expansion procedures, improved in-vivo signalling, and augmentation of the cellular milieu, while simultaneously choosing the appropriate transplantation site and technique for introduction of the stem cell graft.

背景与目标： : 使用人脐带血 (HUCB) 作为干细胞种群的来源有很多临床应用。除造血祖细胞外，在人脐带血中还发现了各种数量的间充质，内皮干细胞和神经元前体。这些可能在诸如免疫缺陷和自身免疫性疾病等疾病中有用。考虑到安全性，可用性，移植方法，排斥反应和副作用等问题，有人认为，利用HUCB干细胞的治疗性干细胞移植提供了可靠的早期前体细胞储存库，可用于多种多样的条件。可以通过体外扩增程序，改善体内信号传导和增加细胞环境，同时选择合适的移植部位和技术来引入脐带血，减轻脐带血中相对较少数量的单核细胞的缺点。干细胞移植物。

BACKGROUND & AIMS: :A mechanistic understanding of adipose tissue differentiation is critical for the treatment and prevention of obesity and type 2 diabetes. Conventional in vitro models of adipogenesis are preadipocytes or freshly isolated adipocytes grown in two-dimensional (2D) cultures. Optimal results using in vitro tissue culture models can be expected only when adipocyte models closely resemble adipose tissue in vivo. Thus the design of an in vitro three-dimensional (3D) model which faithfully mimics the in vivo environment is needed to effectively study adipogenesis. Pluripotent embryonic stem (ES) cells are a self-renewing cell type that can readily be differentiated into adipocytes. In this study, a 3D culture system was developed to mimic the geometry of adipose tissue in vivo. Murine ES cells were seeded into electrospun polycaprolactone scaffolds and differentiated into adipocytes in situ by hormone induction as demonstrated using a battery of gene and protein expression markers along with the accumulation of neutral lipid droplets. Insulin-responsive Akt phosphorylation, and beta-adrenergic stimulation of cyclic AMP synthesis were demonstrated in ES cell-derived adipocytes. Morphologically, ES cell-derived adipocytes resembled native fat cells by scanning electron and phase contrast microscopy. This tissue engineered ES cell-matrix model has potential uses in drug screening and other therapeutic developments.

背景与目标： : 对脂肪组织分化的机械理解对于治疗和预防肥胖和2型糖尿病至关重要。常规的脂肪生成体外模型是在二维 (2D) 培养物中生长的前脂肪细胞或新鲜分离的脂肪细胞。仅当脂肪细胞模型与体内脂肪组织非常相似时，才能预期使用体外组织培养模型的最佳结果。因此，需要设计忠实地模仿体内环境的体外三维 (3D) 模型来有效地研究脂肪形成。多能胚胎干 (ES) 细胞是一种自我更新的细胞类型，可以很容易地分化为脂肪细胞。在这项研究中，开发了3D培养系统来模拟体内脂肪组织的几何形状。将鼠ES细胞接种到电纺聚己内酯支架中，并通过激素诱导原位分化为脂肪细胞，如使用一系列基因和蛋白质表达标记以及中性脂质滴的积累所证明的那样。在ES细胞衍生的脂肪细胞中证实了胰岛素反应性Akt磷酸化和 β-肾上腺素能刺激环状AMP合成。通过扫描电子和相差显微镜，从形态上讲，ES细胞衍生的脂肪细胞类似于天然脂肪细胞。这种组织工程的ES细胞基质模型在药物筛选和其他治疗开发中具有潜在用途。

BACKGROUND & AIMS: :Acute kidney injury is followed by regeneration of damaged renal tubular epithelial cells. The purpose of this study was to test the hypothesis that renal stem cells exist in the adult kidney and participate in the repair process. A unique population of cells that behave in a manner that is consistent with a renal stem cell were isolated from rat kidneys and were termed multipotent renal progenitor cells (MRPC). Features of these cells include spindle-shaped morphology; self-renewal for >200 population doublings without evidence for senescence; normal karyotype and DNA analysis; and expression of vimentin, CD90 (thy1.1), Pax-2, and Oct4 but not cytokeratin, MHC class I or II, or other markers of more differentiated cells. MRPC exhibit plasticity that is demonstrated by the ability of the cells to be induced to express endothelial, hepatocyte, and neural markers by reverse transcriptase-PCR and immunohistochemistry. The cells can differentiate into renal tubules when injected under the capsule of an uninjured kidney or intra-arterially after renal ischemia-reperfusion injury. Oct4 expression was seen in some tubular cells in the adult kidney, suggesting these cells may be candidate renal stem cells. It is proposed that MRPC participate in the regenerative response of the kidney to acute injury.

背景与目标： : 急性肾损伤后，受损的肾小管上皮细胞再生。目的检验肾干细胞存在于成人肾脏并参与修复过程的假说。从大鼠肾脏中分离出一种独特的细胞群，其行为方式与肾干细胞一致，被称为多能肾祖细胞 (MRPC)。这些细胞的特征包括梭形形态;> 200种群倍增的自我更新，没有衰老的证据; 正常的核型和DNA分析; 波形蛋白，CD90 (thy1.1)，Pax-2和10月4的表达，而不是细胞角蛋白，MHC I或II类，或更多分化细胞的其他标记。MRPC表现出可塑性，通过逆转录酶PCR和免疫组织化学诱导细胞表达内皮，肝细胞和神经标志物的能力证明了这种可塑性。当在未受伤的肾脏的胶囊下注射或在肾缺血再灌注损伤后动脉内注射时，细胞可以分化为肾小管。在成人肾脏的某些肾小管细胞中观察到10月4的表达，表明这些细胞可能是候选的肾干细胞。建议MRPC参与肾脏对急性损伤的再生反应。

BACKGROUND & AIMS: OBJECTIVE:The purpose of this study was to use serial thin-section CT scans to assess the incidence of respiratory viral infection and lung abnormalities in a large patient population at high risk of pulmonary complications. MATERIALS AND METHODS:The study population consisted of 26 recipients of hematopoietic stem cell transplants who had proven respiratory viral pneumonia. In all cases, thin-section CT scans were obtained before fiberoptic bronchoscopy and bronchoalveolar lavage. The study included only patients in whom bronchoalveolar lavage fluid showed no evidence of organisms other than respiratory viruses. The CT scans were assessed for the presence, extent, and anatomic distribution of ground-glass attenuation, air-space consolidation, nodules, centrilobular branching structures (tree-in-bud), thickening of the bronchovascular bundles, and pleural effusion. RESULTS:Areas of ground-glass attenuation were identified in 24 (92%) of 26 patients and were the only finding in eight patients. Multiple nodules, seen in 17 (65%) of 26 patients, measured 3-10 mm in diameter or were larger than 10 mm. The nodules had a centrilobular or random distribution. A tree-in-bud appearance was seen in six of the patients with centrilobular nodules. This pattern had a bilateral distribution and involved mainly the lower lung zones. CT revealed thickening of the bronchovascular bundles in 16 (61%) of the patients. Thickening was bilateral in 14 and unilateral in two patients. Bronchial wall thickening involved the lower lobes in six patients and had a patchy random distribution in the remaining nine patients. Air-space consolidation was present in nine (35%) of the cases. It had a lobular or subsegmental distribution in eight of the patients and a segmental distribution in one patient. Areas of consolidation were randomly distributed throughout the lungs in all cases. Less common findings included bilateral pleural effusion and bronchial dilatation. CONCLUSION:Respiratory viral infection is common among adult recipients of hematopoietic stem cell transplants, occurring over a wide time span after transplantation. The presence of respiratory viral infection must be considered in any patient with new respiratory symptoms, fever, or findings at CT such as extensive or patchy areas of ground-glass opacities or a mixture of patterns, most commonly ground-glass attenuation, thickening of the bronchial walls, and multiple small nodules.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The rodent specific reproductive homeobox (Rhox) gene cluster on the X chromosome has been reported to contain twelve homeobox-containing genes, Rhox1-12. RESULTS:We have identified a 40 kb genomic region within the Rhox cluster that is duplicated eight times in tandem resulting in the presence of eight paralogues of Rhox2 and Rhox3 and seven paralogues of Rhox4. Transcripts have been identified for the majority of these paralogues and all but three are predicted to produce full-length proteins with functional potential. We predict that there are a total of thirty-two Rhox genes at this genomic location, making it the most gene-rich homoeobox cluster identified in any species. From the 95% sequence similarity between the eight duplicated genomic regions and the synonymous substitution rate of the Rhox2, 3 and 4 paralogues we predict that the duplications occurred after divergence of mouse and rat and represent the youngest homoeobox cluster identified to date. Molecular evolutionary analysis reveals that this cluster is an actively evolving region with Rhox2 and 4 paralogues under diversifying selection and Rhox3 evolving neutrally. The biological importance of this duplication is emphasised by the identification of an important role for Rhox2 and Rhox4 in regulating the initial stages of embryonic stem (ES) cell differentiation. CONCLUSION:The gene rich Rhox cluster provides the mouse with significant biological novelty that we predict could provide a substrate for speciation. Moreover, this unique cluster may explain species differences in ES cell derivation and maintenance between mouse, rat and human.

背景与目标：

BACKGROUND & AIMS: PROBLEM:Lymphocyte immunotherapy (LIT) is applied in infertility treatment. Moreover, it has been suggested for prevention of rhesus D-hemolytic disease and as a vaccine for reduction of human immunodeficiency virus-1 susceptibility. Although transfusion-related problems have been rarely reported they were a matter of debate. Here we discuss extensive single-center experience with intradermal LIT for implantation failure and recurrent miscarriages. METHOD OF STUDY:Retrospective 2- to 3-year follow-up of in vitro fertilization couples treated during 1996-2002 (feedback 2,848/3,041 = 93%), registering 930 deliveries. Prospective survey for acute reactions for 2000-2003 (feedback 2,687/3,246 = 83%). Review of the literature. RESULTS:Infections of the patient and transplant rejection later in life are minor residual risks. Post-transfusion purpura was suspected once but not verified. Anaphylaxis or malignancy were not promoted. Fetal/newborn alloimmune disease (severe hemolytic disease, thrombocytopenia, neutropenia) were not observed. CONCLUSION:Based on microbiological, immunological, and hematological testing the risks of intradermal LIT are low.

背景与目标：

BACKGROUND & AIMS: :Thyroid hormone (TH) regulates such crucial biological functions as normal growth, development and metabolism of nearly all vertebrate tissues. In skeletal muscle, TH plays a critical role in regulating the function of satellite cells, the bona fide skeletal muscle stem cells. Deiodinases (D2 and D3) have been found to modulate the expression of various TH target genes in satellite cells. Regulation of the expression and activity of the deiodinases constitutes a cell-autonomous, pre-receptor mechanism that controls crucial steps during the various phases of myogenesis. Here, we review the roles of deiodinases in skeletal muscle stem cells, particularly in muscle homeostasis and upon regeneration. We focus on the role of T3 in stem cell functions and in commitment towards lineage progression. We also discuss how deiodinases might be therapeutically exploited to improve satellite-cell-mediated muscle repair in skeletal muscle disorders or injury.

背景与目标： : 甲状腺激素 (TH) 调节着几乎所有脊椎动物组织的正常生长，发育和代谢等关键的生物学功能。在骨骼肌中，TH在调节卫星细胞 (真正的骨骼肌干细胞) 的功能中起着至关重要的作用。已发现脱碘酶 (D2和D3) 调节卫星细胞中各种TH靶基因的表达。调节脱碘酶的表达和活性构成了一种细胞自主的前受体机制，该机制控制着肌发生各个阶段的关键步骤。在这里，我们回顾了脱碘酶在骨骼肌干细胞中的作用，特别是在肌肉稳态和再生中的作用。我们专注于T3在干细胞功能和对谱系进展的承诺中的作用。我们还讨论了如何在治疗上利用脱碘酶来改善骨骼肌疾病或损伤中的卫星细胞介导的肌肉修复。

BACKGROUND & AIMS: AIM:During development, boundary cap neural crest stem cells (bNCSCs) assist sensory axon growth into the spinal cord. Here we repositioned them to test if they assist regeneration of sensory axons in adult mice after dorsal root avulsion injury. MATERIALS & METHODS:Avulsed mice received bNCSC or human neural progenitor (hNP) cell transplants and their contributions to glial scar formation and sensory axon regeneration were analyzed with immunohistochemistry and transganglionic tracing. RESULTS:hNPs and bNCSCs form similar gaps in the glial scar, but unlike hNPs, bNCSCs contribute Mts1/S100A4 (calcium-binding protein) expression to the scar and do not assist sensory axon regeneration. CONCLUSION:bNCSC transplants contribute nonpermissive Mts1/S100A4-expressing cells to the glial scar after dorsal root avulsion.

背景与目标：

BACKGROUND & AIMS: :The unmet need for therapies capable of repairing the central nervous system (CNS) damage occurring in many diseases including multiple sclerosis (MS) has sparked the interest of the neurological community for stem cell-based therapies. An exhaustive amount of preclinical data has shown that the intravenous administration of mesenchymal stem cells (MSC), a subset of progenitor cells isolated from many mesodermal tissues, effectively ameliorates experimental autoimmune encephalomyelitis (EAE), a model of MS, through the release of anti-inflammatory and neuroprotective molecules. Based on these results, several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair as realized clinically, with functional recovery, or visualized by magnetic resonance imaging (MRI).

背景与目标： : 对能够修复包括多发性硬化症 (MS) 在内的许多疾病中发生的中枢神经系统 (CNS) 损伤的疗法的未满足需求，引发了神经学界对基于干细胞的疗法的兴趣。大量的临床前数据表明，静脉内施用间充质干细胞 (MSC) (从许多中胚层组织中分离出的祖细胞的子集) 通过释放有效地改善了MS模型的实验性自身免疫性脑脊髓炎 (EAE) 炎症和神经保护分子。基于这些结果，在患有晚期MS的受试者中进行的一些小型试点临床试验表明，MSC给药是安全的，并提供了临床有效性的早期信号。对基于MSC的MS治疗策略的开发感兴趣的临床医生和科学家目前的目标是在大型临床试验中最终证明MSC可以抑制CNS炎症并促进组织修复，如临床实现的那样，具有功能恢复，或通过磁共振成像 (MRI) 可视化。

BACKGROUND & AIMS: :Upregulation of lipogenesis is a hallmark of cancer and blocking the lipogenic pathway is known to cause tumor cell death by apoptosis. However, the exact role of lipogenesis in tumor initiation is as yet poorly understood. We examined the expression profile of key lipogenic genes in clinical samples of ductal carcinoma in situ (DCIS) of breast cancer and found that these genes were significantly upregulated in DCIS. We also isolated cancer stem-like cells (CSCs) from DCIS.com cell line using cell surface markers (CS24(-)CD44(+)ESA(+)) and found that this cell population has significantly higher tumor-initiating ability to generate DCIS compared with the non-stem-like population. Furthermore, the CSCs showed significantly higher level of expression of all lipogenic genes than the counterpart population from non-tumorigenic breast cancer cell line, MCF10A. Importantly, ectopic expression of SREBP1, the master regulator of lipogenic genes, in MCF10A significantly enhanced lipogenesis in stem-like cells and promoted cell growth as well as mammosphere formation. Moreover, SREBP1 expression significantly increased the ability of cell survival of CSCs from MCF10AT, another cell line that is capable of generating DCIS, in mouse and in cell culture. These results indicate that upregulation of lipogenesis is a pre-requisite for DCIS formation by endowing the ability of cell survival. We have also shown that resveratrol was capable of blocking the lipogenic gene expression in CSCs and significantly suppressed their ability to generate DCIS in animals, which provides us with a strong rationale to use this agent for chemoprevention against DCIS.

背景与目标： : 脂肪生成的上调是癌症的标志，已知阻断脂肪生成途径会通过凋亡导致肿瘤细胞死亡。然而，脂肪生成在肿瘤起始中的确切作用尚不清楚。我们检查了乳腺癌导管原位癌 (DCIS) 临床样本中关键脂原基因的表达谱，发现这些基因在DCIS中显着上调。我们还使用细胞表面标记 (CS24(-)CD44(+)ESA(+)) 从DCIS.com细胞系中分离出癌症干细胞样细胞 (CSCs)，发现该细胞群与非干细胞样群体相比，产生DCIS的肿瘤起始能力明显更高。此外，与来自非致瘤性乳腺癌细胞系MCF10A的对应群体相比，CSCs显示出所有脂质基因的表达水平显着更高。重要的是，MCF10A中脂肪生成基因的主要调节剂SREBP1的异位表达显着增强了干细胞样细胞的脂肪生成，并促进了细胞生长和mammohere形成。此外，SREBP1的表达显着提高了MCF10AT (另一种能够产生DCIS的细胞系) 在小鼠和细胞培养中的CSCs的细胞存活能力。这些结果表明，通过赋予细胞存活能力，脂肪生成的上调是DCIS形成的先决条件。我们还表明，白藜芦醇能够阻断CSCs中的脂肪基因表达，并显着抑制其在动物中产生DCIS的能力，这为我们提供了使用该药物对DCIS进行化学预防的有力依据。

BACKGROUND & AIMS: :Satellite cells, localized within muscles in vivo, are Pax7+ muscle stem cells supporting skeletal muscle growth and regeneration. Unfortunately, their amplification in vitro, required for their therapeutic use, is associated with reduced regenerative potential. In the present study, we investigated if human myogenic reserve cells (MRC) obtained in vitro, represented a reliable cell source for muscle repair. For this purpose, primary human myoblasts were freshly isolated and expanded. After 2 days of differentiation, 62 ± 2.9% of the nuclei were localized in myotubes and 38 ± 2.9% in the mononucleated non-fusing MRC. Eighty percent of freshly isolated human MRC expressed a phenotype similar to human quiescent satellite cells (CD56+/Pax7+/MyoD-/Ki67- cells). Fourteen days and 21 days after cell transplantation in immunodeficient mice, live human cells were significantly more numerous and the percentage of Pax7+/human lamin A/C+ cells was 2 fold higher in muscles of animals injected with MRC compared to those injected with human myoblasts, despite that percentage of spectrin+ and lamin A/C+ human fibers in both groups MRC were similar. Taken together, these data provide evidence that MRC generated in vitro represent a promising source of cells for improving regeneration of injured skeletal muscles.

背景与目标： : 体内定位在肌肉内的卫星细胞是Pax7 + 肌肉干细胞，支持骨骼肌生长和再生。不幸的是，其治疗用途所需的体外扩增与再生潜力降低有关。在本研究中，我们研究了体外获得的人肌源性储备细胞 (MRC) 是否代表了用于肌肉修复的可靠细胞来源。为此，新鲜分离并扩增了原代人类成肌细胞。分化2天后，62个nuclei ±   2.9% 的细胞核位于肌管中，38个   ±   2.9% 位于单核非融合MRC中。80% 的新鲜分离的人MRC表达的表型类似于人静止卫星细胞 (CD56/Pax7/MyoD-/Ki67-细胞)。免疫缺陷小鼠细胞移植后14天和21天，活人细胞数量明显增加，注射MRC的动物肌肉中Pax7 +/人lamin A/C + 细胞的百分比比注射人成肌细胞高2倍，尽管两组MRC中spectrin和lamin A/C人类纤维的百分比相似。总之，这些数据提供了证据，表明体外产生的MRC代表了改善受损骨骼肌再生的有希望的细胞来源。