Retinoids induce differentiation of type A spermatogonia in vitro: organ culture of mouse cryptorchid testes

To study the effects of retinoids on testicular germ cell differentiation, especially on stem cells, artificially induced cryptorchid testes of adult mice were cultured in vitro inasmuch as they contain only stem cells, type A spermatogonia. We report here that retinol, retinal, retinol acetate, even retinoic acid, activated cell division in type A spermatogonia and stimulated them to differentiate. These findings are the first demonstration of the in vitro induction of early stage of spermatogenesis by retinoids and also retinoic acid, which is considered to be a biochemically inactive compound for mammalian testicular function.     

干细胞向雌性生殖细胞分化的研究进展

干细胞是一类具有自我更新和多向分化潜能的细胞。根据其来源不同,干细胞可分为胚胎干细胞、成体干细胞以及诱导性多能干细胞。生殖细胞系负责跨代传递遗传和表观遗传信息,以确保新的正常个体产生。人类辅助生殖技术(ART)虽可解决部分难治性不孕不育患者的生育问题,但尚不能解决由于卵巢早衰生殖细胞缺乏导致的不孕,如果在体外可以将干细胞定向诱导分化为生殖细胞,则可能通过ART帮助卵巢早衰患者获得健康后代。雌性配子发育经历了多个严格、复杂的过程,包括原始生殖细胞(PGC)特化、增殖、迁移到生殖嵴并最终分化为成熟的卵母细胞。然而具体过程尚不明确。近年来学者已建立了干细胞向雌性生殖细胞分化的体外模型,并取得了长足进步。     

卵巢生殖干细胞研究进展

研究显示,卵巢中可能存在具有自我更新和分化潜能的生殖干细胞,尽管数量很少,但能产生新的卵母细胞和维持始基卵泡发生。对生殖干细胞的分离培养及其分化调控的研究将会加深研究者对生殖生理的认识,并为保留卵巢恶性肿瘤患者的生育功能及对卵巢性不孕症的治疗提供新的策略。     

CD133在子宫内膜癌中的研究进展

女性生殖道恶性肿瘤严重危及女性健康,子宫内膜癌(endometrial cancer,EC)占妇科恶性肿瘤的20%～30%。同其他恶性肿瘤一样具有侵袭和转移的特性,且远处转移是影响其预后的重要因素。目前提出的"肿瘤干细胞理论"认为,子宫内膜癌肿瘤组织中也存在少量具有自我更新、无限分化和增殖的肿瘤干细胞,这些干细胞可能是子宫内膜癌发生、转移和复发的关键。CD133作为一个公认的新型肿瘤干细胞的标记物在多种肿瘤组织中表达,同样也有望成为子宫内膜癌干细胞的特异性标记物及评估子宫内膜癌预后的有效标记物。     

间充质干细胞治疗心脏疾患的研究进展

间充质干细胞(mesenchymal stem cells,MSCs)存在于多种组织内,是一种具有自我增殖和多项分化潜能的成体干细胞。MSCs体外易培养,且具有免疫调节特性,使其成为实现组织再生的种子细胞。动物心肌梗死模型证实MSCs体内移植,能够分化为心肌细胞和血管细胞,募集内源性心肌干细胞,分泌系列细胞因子,这些特性能够防止和逆转心室重构。Ⅰ期临床试验表明MSCs移植具有提高左室射血分数、抑制心室重构、减少瘢痕面积的作用。     

神经干细胞移植的方法选择及其在脊髓损伤中的应用

脊髓损伤是一种创伤性中枢神经系疾病,常伴有脊髓损伤平面以下感觉、运动、自主神经功能丧失,常导致患者终身残疾,且并发症较多,甚至死亡。至今尚无有效的治疗方法从根本上修复已损伤的脊髓功能。神经干细胞具有自我更新、增殖和多向分化等潜能,其移植后可向神经元分化并替代已坏死的神经元,形成新的突触,重建神经通路促进脊髓功能的修复,为脊髓损伤患者的康复带来曙光。近年来许多科学家对神经干细胞进行基因修饰,基因调控,或联合其他细胞、生物材料以及改变移植时间、途径等多方面进行深入研究,来提高移植效率,虽然取得了长足的进展,但仍存在一些不足之处尚待进一步完善,如神经干细胞移植的途径、时机、次数的相关标准,移植细胞的免疫排斥、长期存活、定向分化,神经干细胞的来源及伦理,移植的安全性等。本文拟对神经干细胞移植方法,移植时间,移植途径进行综述,并对神经干细胞移植所存在的问题及应用前景进行展望。     

胚胎干细胞向子宫内膜样细胞分化中Wnt信号通路的调控作用

人胚胎干细胞是人体内最原始的细胞,具有自我更新和分化为各种细胞的潜能,而信号通路在细胞的形态和功能变化中起着重要的协调和控制作用。目前的研究已经证实,Wnt信号通路在女性生殖系统的发育中起着重要的作用,是其分化形成的关键因子,在胚胎干细胞定向分化为子宫内膜样细胞的过程中,Wnt信号通路同样起着关键的调控作用。综述Wnt信号通路在人胚胎干细胞向子宫内膜样细胞分化过程中所起的作用,并展望今后对其的研究方向。     

Research advances in the regulation of the putative ovarian germline stem cell niche on female germline stem cells

Stem cells are ideal seeding cells, which have the potential for self-renewal and multiple differentiation, and they play a fundamental role in maintaining homeostasis and regenerating and repairing tissue. The discovery of female germline stem cells (FGSCs) brings much hope for the postnatal renewal of oocytes and solving some female infertility problems. Ovarian function declines with increasing female age. Moreover, ovarian germline stem cell niche-aging could be the main cause of ovarian senescence, which ultimately leads to decreased follicle generation, declining female fertility, and age-related diseases, such as osteoporosis and ovarian cancer. The ovarian germline stem cell niche is the surrounding microenvironment in which FGSCs live, and it helps control the biological characteristics of FGSCs in many ways, such as nutritional supply and immunological cytokine secretion. This paper reviews the knowledge about the ovarian germline stem cell niche and its probable regulatory mechanisms on FGSCs, which provides valuable scientific information and scope for the prevention and treatment of ovarian senescence.

Abbreviations: BMP: bone morphogenetic protein; Dpp: decapentaplegic; FGSC: female germline stem cell; IL, interleukin; OGSC: ovarian germline stem cells; ROS: reactive oxygen species; TGF, transforming growth factor; TNF, tumor necrosis factor     

脐带间充质干细胞与脐血造血干细胞临床应用的研究进展

人胚胎干细胞(HESC)系及生殖细胞系的建立,被美国时代周刊(Times)列为20世纪世界十大科技成就之首。脐带间充质干细胞(UC-MSC)和脐血造血干细胞(UCB-HSC)的研究作为其中的一部分,具有广阔的临床应用前景。UC-MSC和UCB-HSC是具有自我更新、分化能力和产生多系或单系特异细胞功能的细胞,位于细胞发育谱系的顶端。笔者拟对UC-MSC和UCB-HSC的来源、生物学特点及其临床应用等方面的进展,综述如下。     

苯乙基异硫氰酸盐对小鼠胚胎干细胞分化为神经细胞过程中基因表达影响的研究

目的探讨苯乙基异硫氰酸盐(PEITC)对小鼠胚胎干细胞(mESCs)体外定向诱导分化为神经样细胞中PKCα及其相关发育基因(pax-6、netrin-1)表达的影响。方法mESCs经RA法诱导后,第7天用RT-PCR法检测nestin、glutaminase、Brn-3基因等神经细胞特异性标志物。不同浓度PEITC作用条件下,分别取诱导后1、3、5、7及14天后的细胞,用RT-PCR方法测定细胞的PKCα及其相关发育基因pax-6和netrin-1的mRNA表达情况。结果诱导后第7天,分化的神经样细胞中nestin、glutaminase、Brn-3基因均高表达。正常诱导1天后,PKCα、pax-6和netrin-1基因的mRNA表达急剧下降,3、5、7天逐渐升高,至14天恢复至正常水平。PEITC作用下,PKCα、pax-6、netrin-1的mRNA在诱导后细胞中各阶段的表达水平与正常诱导条件下相比均下降,且随着作用浓度和作用时间的增加,下降趋势明显。结论PEITC对mESCs定向分化为神经样细胞过程中相关发育基因(pax-6、netrin-1)的表达的干扰作用可能与抑制PKCα的表达有关。     

Identification of a Membrane Receptor for Retinol-Binding Protein Functioning in the Cellular Uptake of Retinal

Retinol-binding protein (RBP) is the transport protein that carries retinol in the circulation from the liver to its target tissues. The existence of a cell-surface receptor on the target cells, which mediates the uptake of retinol from RBP, has been known since 1975. Recently, it was identified as an integral transmem-brane protein named STRA6 that is inducible by retinoic acid in certain cancer cells. The receptor was found to be highly specific for RBP, with high affinity, and to be localized in all tissues known to require retinol for their function, particularly the pigment epithelium of the eye.     

卵巢生殖干细胞研究进展

研究显示,卵巢中可能存在具有自我更新和分化潜能的生殖干细胞,尽管数量很少,但能产生新的卵母细胞和维持始基卵泡发生。对生殖干细胞的分离培养及其分化调控的研究将会加深研究者对生殖生理的认识,并为保留卵巢恶性肿瘤患者的生育功能及对卵巢性不孕症的治疗提供新的策略。     

胚胎干细胞及诱导多能干细胞在胚胎毒性研究中的应用

药物对于生殖细胞或者早期胚胎的影响将会引起不孕或者种植前胚胎的发育异常,进而引起胚胎毒性或者是后代的畸形,因此药物的临床应用需要有可靠的实验数据证明其对胚胎的影响,而胚胎干细胞(embryonic stem cell,ESC)由于其无限增殖及多向分化的潜能而作为研究药物胚胎毒性的细胞模型得到广泛应用,以ESC为基础的胚胎干细胞实验(embryonic stem cell test,EST)是获得国际认可的胚胎毒性评价的体外替代方法,但是该实验方法的快速性和准确性存在一定的局限性,目前该细胞模型的研究主要集中于快速性和准确性的优化。新兴的诱导多能干细胞(induced pluripotent stem cells,i PSC),由于具有与ESC相似的增殖和分化特性,目前也被逐步应用于药物胚胎毒性的研究。     

Retinoid metabolism in the rat small intestine

Vitamin A (retinol) is essential for epithelial cell growth, differentiation and proliferation. The absorption of retinol occurs in the small intestine, and the metabolism of this vitamin is not well studied in this organ. The intestinal epithelium has a high rate of cell proliferation and differentiation, and the present study looked at the level of retinoids and metabolizing enzymes involved in their interconversion along the villus-crypt axis under normal conditions. Intestine was removed from control rats, and enterocytes at various stages of maturation and differentiation were quantified by the metal chelation method. Using HPLC, various retinoid concentrations in the cell homogenate and the metabolizing enzymes in the cytosol were quantified. The proliferating crypt cells were found to have a higher level of retinoic acid as well as of the enzymes involved in its formation, such as retinaldehyde oxidase and retinol dehydrogenase, compared with the villus cells, suggesting a possible role for this compound in intestinal epithelial cell proliferation and differentiation. The high level of retinol and high retinaldehyde reductase activity in the villus cells suggest the important role played by this enzyme in the conversion of dietary beta-carotene to retinol via retinaldehyde. In summary, this study has given for the first time a detailed analysis of the retinoid levels and metabolizing enzymes in different cell populations in the rat small intestinal epithelium.     

人宫颈癌干细胞的分离鉴定

目的:通过分选人宫颈癌细胞中的侧群细胞验证其肿瘤干细胞特性。方法:取16例行宫颈鳞癌切除的手术标本进行宫颈癌细胞原代培养,流式细胞仪分选侧群细胞(Side Population,SP),对比SP细胞和非SP细胞(Non Side Population,Non-SP)的体外自我更新能力和肿瘤形成能力。结果:在原代培养的16株宫颈癌细胞中均分选出SP细胞,比例约占(1.67±0.94)%。SP细胞的克隆形成能力显著高于NSP细胞,SP细胞在裸鼠肿瘤形成能力显著高于NSP细胞。结论:人宫颈癌侧群细胞具有肿瘤干细胞特性,为宫颈癌干细胞的研究提供了简单、有效的分离方法。     

干细胞治疗薄型子宫内膜的研究进展

在辅助生殖技术中,子宫内膜厚度可以反映内膜功能状态,薄型子宫内膜是指子宫内膜厚度不足以获得胚胎着床及临床妊娠。虽然临床对薄型子宫内膜治疗的方式较多,但总体治疗效果欠佳。干细胞因具有多向分化和自我更新的潜能而展现出广阔的发展前景,包括胚胎干细胞、成体干细胞和诱导多能干细胞,随着对干细胞研究的深入,目前有研究诱导干细胞向子宫内膜细胞定向分化并增生,以促进子宫内膜生长,进而用于治疗薄型子宫内膜。现主要就骨髓间质干细胞（BMSCs）、子宫内膜干细胞（EDSCs）、人胚胎干细胞（hESCs）及人脐带华通胶间充质干细胞（WJ-MSCs）在薄型子宫内膜治疗的研究进展以及这4种细胞用于临床治疗的优缺点进行综述。     

体外诱导胚胎干细胞分化为神经细胞特性的实验研究

目的研究体外利用全反视黄酸(RA)诱导小鼠胚胎干细胞(mESC)分化为神经细胞的培养方法。方法悬滴3天转悬浮1天两者结合的培养方法得到胚体(EBs),再利用RA对其处理4天后,进行免疫组织化学、RT-PCR以及兴奋性功能的检测,观察神经细胞获得的效率及其生理特性。结果利用RA诱导方法得到的神经细胞,免疫组化表明nestin蛋白表达的阳性率为(53.49±6.02)%,且RT-PCR法分析其能表达nestin、glutaminase和Brn-3等神经细胞特异基因,同时在Glu刺激下具有与脑来源神经元相似的特性和功能。结论利用本实验诱导方法,获得神经细胞的比例较高,且具有与神经元相似的生物学特性。