Induced pluripotent stem cells

Induced pluripotent stem (iPS) cells are a recent development which has brought a promise of great therapeutic values. The previous technique of somatic cell nuclear transfer (SCNT) has been ineffective in humans. Recent discoveries show that human fibroblasts can be reprogrammed by a transient over expression of a small number of genes; they can undergo induced pluripotency. iPS were first produced in 2006. By 2008, work was underway to remove the potential oncogenes from their structure. In 2009, protein iPS (piPS) cells were discovered. Surface markers and reporter genes play an important role in stem cell research. Clinical applications include generation of self renewing stem cells, tissue replacement and many more. Stem cell therapy has the ability to dramatically change the treatment of human diseases.

     

脂肪干细胞的分化功能及在组织修复中的应用

成体干细胞有巨大的潜能治疗多种疾病,细胞疗法和再生医学为治疗组织缺损和器官损伤提供了新思路,脂肪干细胞(ADSCs)与胚胎干细胞(ESCs)、诱导多能干细胞(iPSCs)及骨髓干细胞(BMSCs)为比较理想的类型。通过查阅一定量的文献我们了解到,获取脂肪干细胞的方法对人体的损伤最小,且含量丰富,也不受到伦理道德、识别困难等问题的限制并易于扩增。同时ADSCs在不同的条件下能够分化成脂肪细胞、成骨细胞、软骨细胞、肌细胞、神经细胞。这些特性为脂肪干细胞移植治疗软组织缺损和难愈合伤口提供了一种选择,并且在美容外科也有一定的应用。现在对目前脂肪干细胞的分离、分化和治疗进行阐述。     

The advancement of stem cell transplantation to treat acute myocardial infarction

The current findings have provided compelling evidence that a specific opulation of cells derived from bone marrow,stem cells,might hold the key to producing functional cardiac cells in damaged hearts. This cellular therapeutics intervention reduced the infracted area and improved cardiac haemodynamics. Our rhesus monkey studies have also confirmed that stem cells transplantation therapy can improve the infarcted cardiac functions. Recent interest has focused on not only the development of stem cells as a therapeutic option in treatment of the disease,but also the mobilization of bone marrow cells repairing the infarcted heart,and try to get no immune-rejection cardiomyocyte engrafts.The objective of this review is to describe the derivation and unique properties of human ES cells.Particular emphasis well be given to summarizing recent studies that focus on the potential of human ES cells for differentiation into cardiomyocyte in vitro and in vivo,especially the advancement of stem cells transplantation for treating AMI.We will also outline key scientific questions that will need to be answered before the full therapeutic potential of human ES cells can be used.     

Therapeutic potential of motor neurons differentiated from embryonic stem cells and induced pluripotent stem cells

Degeneration of motor neurons (MN) caused by disease or injury leads to paralysis and is fatal in some conditions. To date, there are no effective treatments for MN disorders; therefore, cell therapy is a promising strategy to replace lost MN. Embryonic stem (ES) cells isolated from the inner cell mass of mammalian blastocysts self-renew and are pluripotent because they differentiate into cell types of the three germinal layers. Reprogramming of adult cells to a state similar to ES cells, termed induced pluripotent stem (iPS) cells, has been recently reported. It is well established that pluripotent cell types can give rise to specialized phenotypes, including neurons. Mouse, monkey and human MN can be differentiated from ES and iPS cells using procedures generally involving embryoid bodies formation and stimulation with retinoic acid and Sonic hedgehog. Differentiated MN express characteristic molecular markers such as Islet1, HB9 and Choline acetyltransferase, exhibit electrophysiological maturity and are able to form synaptic contacts similar to neuromuscular junctions in vitro. Furthermore, transplanted MN promote functional recovery in animal models of neurodegenerative diseases and MN injury. The potential clinical applications of stem cell-derived MN was enhanced after iPS cell derivation, which makes possible the generation of patient-specific pluripotent cells for autologous cell replacement therapies and may be used for drug development and disease modeling. This review summarizes MN differentiation protocols from ES and iPS cells in regard to neuronal differentiation efficiency, expression of MN markers and functional properties in vitro, as well as their therapeutic effects after grafting.     

干细胞与皮肤创伤愈合

皮肤直接与外界接触，易于受伤，并且皮肤创伤愈合较为复杂，因此，研究皮肤创伤愈合具有重要的理论和实际意义。干细胞在多种生理和病理情况下都发挥了重要作用，在皮肤创伤愈合中也具有重要意义。本文综述了与皮肤创伤愈合密切相关的干细胞研究进展。     

Wnt和Notch信号通路在肺癌干细胞调控中的研究进展

肿瘤干细胞是具有自我更新和多向分化潜能的少部分未分化细胞,在多种肿瘤的发生、发展中发挥重要作用。肺癌干细胞被认为是肺癌发生的根源,具有自我更新、分化、转移、致瘤性等特征。已有研究表明,肺癌干细胞受自身内在基因和其所处微环境信号的共同调控,两条经典的发育调控通路Wnt、Notch在其中发挥重要作用。深入研究Wnt和Notch信号通路在肺癌干细胞调控中的作用,有望在肺癌的诊断及治疗中找到新靶点。     

人干细胞的分化研究及临床应用探索

人干细胞是具有自我复制和分化潜能的细胞,有很多种类,在人体发育中起着决定性的作用.干细胞的分化是干细胞研究的核心内容,除了受干细胞自身分化潜能制约外,同时受干细胞周围环境的控制.人干细胞的分化研究分为体外研究和体内研究,除观察人干细胞诱导分化后的形态变化外,同时也探索细胞分化的分子机制.人们关注人干细胞的研究,目的就是体外扩增干细胞并获得具有定向分化能力的干细胞,采用适当的手段治疗人类疾病,维护人体健康.     

白血病靶向治疗新进展

白血病的传统治疗通常是采用细胞毒药物联合化疗配合造血干细胞移植。近年来随着分子生物学及抗体工程技术的兴起,只杀伤肿瘤细胞而正常细胞不受到损害的白血病的靶向治疗得到了广泛地关注和发展,本文总结了近来研究较多的靶向治疗,有的已进入了Ⅰ、Ⅱ期临床试验,这些方法对于研究针对白血病细胞特异性靶点的新药,开发新的治疗模式,有选择性地去除白血病细胞、克服耐药,提高患者的无病生存率有着深远的意义和作用。     

Tissue engineering: current strategies and future directions

Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, or other clinical issues. Currently, patients with diseased and injured organs are often treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and as the number of new cases of organ failure increases. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured tissues. In addition, the stem cell field is a rapidly advancing part of regenerative medicine, and new discoveries in this field create new options for this type of therapy. For example, new types of stem cells, such as amniotic fluid and placental stem cells that can circumvent the ethical issues associated with embryonic stem cells, have been discovered. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous, adult cells have already entered the clinical setting, indicating that regenerative medicine holds much promise for the future.     

人脐带间充质干细胞在脊髓损伤修复中的研究进展

脊髓损伤发病率和致残率高,至今尚无完全修复损伤脊髓的治疗方法。随着干细胞移植技术的发展,有望从根本上修复损伤的脊髓。而在所有干细胞中,人脐带间充质干细胞可能是最佳的移植选择。动物研究已证实人脐带间充质干细胞具有巨大的脊髓损伤修复潜力,但临床转化并不顺利。本文将着重讨论人脐带间充质干细胞对脊髓损伤的神经修复机制,以及临床最佳移植途径、剂量、时机和临床安全性、有效性。     

Stem cell plasticity: the growing potential of cellular therapy

The fundamental principle of stem cell biology is that cells with the potential for both self-renewal and terminal differentiation into one or more cell types may be found in a given tissue. The corollary of this principle is that the stem cells give rise to tissues in which they reside, the so-called expected tissues. Many exciting discoveries reported over the last several years challenge this paradigm by showing that there are not only tissue-specific stem cells that differentiate to the expected mature cells, but also that tissue stem cells can differentiate into unexpected cell lineages, suggesting an enormous plasticity of differentiation. Hematopoietic stem cells, which have drawn the most attention, mesenchymal stem cells, and neural stem cells have been the focus of many investigations. However, recent studies directed toward hematopoietic stem cells have disputed the concept of stem cell plasticity, suggesting that experimental artifact or somatic cell fusion may account for reported observations of plasticity. Although the data are mounting, stem cell plasticity, strictly defined, has yet to be rigorously proven. Animal models to meticulously define the biology and potential plasticity of stem cells and pilot clinical trials to begin to explore the biology and therapeutic potential of human stem cells will both be vital to advance the field over the coming years.     

肝干细胞与肝癌关系的研究进展

肝干细胞是肝内具有自我更新、高度增殖和多向分化潜能的成体干细胞,与肝脏发育和再生修复密切相关。近年研究表明,肝干细胞有多种来源,与肝癌的发生密切相关,支持肝癌干细胞来源于正常肝干细胞转化的假说。肝干细胞的研究可能为肝癌靶向治疗提供新的靶点。     

脂肪干细胞：细胞治疗的新选择

成体干细胞在组织修复和再生中具有强大的优势并已成为一种新型的细胞治疗肢体缺血性疾病的细胞来源.本文阐述了关于脂肪组织来源的基质细胞(adipose tissue-derived stromal cells,ADSCs)在组织重建细胞治疗上的巨大潜能.ADSC最大优点在于能方便取得而且容易在体外培养.体外培养的ADSCs能够在特定条件下诱导成为成熟脂肪细胞、骨细胞、神经细胞和内皮细胞.ADSCs还能分泌一定数量的与细胞成熟有关的细胞因子.另外,近年有报道ADSC具有向心肌细胞分化的能力.这些脂肪组织来源的基质细胞有望在不久的将来取代骨髓细胞成为再生细胞治疗的重要材料.     

间充质干细胞归巢的研究进展

间充质干细胞(MSCs)被认为是最有希望治疗多种疾病的一种非造血组织的多能干细胞,具有多向分化潜能,已被证明在临床应用中具有很大的潜能,但是其向靶组织器官归巢率低,且MSCs归巢后的分布和分化直接影响其应用。因此,进一步明确MSCs的归巢机制及归巢的影响因素有助于将MSCs更好地用于临床治疗。     

神经干细胞研究进展

神经干细胞存在于中枢神经系统中,具有自我更新和多方向分化的潜能。近年来神经干细胞疗法成为治疗多种神经系统疾病的新策略,其目的是替代、修复或加强受损细胞的生物学特性。神经干细胞应用主要集中于:直接细胞移植进行神经系统多种疾病的治疗;作为基因载体,进行细胞替代和基因治疗;通过对生长因子和细胞因子的调控,诱导自身神经干细胞分化进行自我修复,广泛应用于帕金森病、脑血管病、脑瘤、脊髓损伤、阿尔茨海默病等疾病的治疗。     

干细胞与转化医学研究进展浅析

干细胞与医学转化是近阶段比较热门的学科。由于干细胞的多种分化潜能和高度的自我更新能力,已经成为修复生命有机体功能细胞的种子细胞,而且在再生医学和组织工程中愈发引起人们的广泛重视。干细胞在临床转换应用的实验研究结果给许多种疾病带来了希望,它克服了临床常规治疗的局限性。目前,干细胞的临床研究处于一个快速的发展阶段,世界各国均高度重视。我国政府对干细胞研究也高度重视,加大了科研的投入,加强了规范化管理,制定了相关政策。如果在干细胞治疗的领域采用转化医学的模式,将科研与临床密切的联系结合,重视在大型实验动物如猪,狗,猴的人类疾病的动物模型的干细胞治疗应用研究,将会促进干细胞临床转化的速度。     

细胞基因重编程在中枢神经损伤修复中的应用

神经干细胞移植替代治疗已经成为治疗中枢神经损伤的一个重要手段,但其细胞来源由于伦理学和免疫排斥等问题而受到了限制.既往研究认为,非神经细胞不能转变成神经细胞.但诱导型多潜能干细胞出现之后,研究发现,通过细胞基因重编程技术可以将鼠和人的自身体细胞诱导转分化为神经干细胞或各种类型的神经元,从而避免了细胞移植治疗中相关的伦理学问题和免疫排斥反应,表明细胞基因重编程在中枢神经损伤修复中具有很好的应用前景.本文对细胞基因重编程技术在诱导神经干细胞或神经元形成方面的相关研究进展及其在中枢神经损伤修复中的应用进行了综述.     

Embryonic stem cell research in Iran: status and ethics

Various successes in regenerative medicine by therapeutic cloning have given rise to expectations that treatments will soon be developed for incurable diseases. But using embryonic stem cells for this purpose raises many ethical dilemmas including those about the beginning of human life. Arguments concerning stem cell research and therapeutic cloning in different countries are influenced by both the religious and bioethical traditions which dominate in these cultures. This article examines how these traditions have influenced stem cell research in Iran through an account of scientific advances and the development of regulations on embryonic stem cell research in Iran.     

Stem cell-based therapy for erectile dysfunction

Objective  To review the effect of stem cells in erectile dysfunction as well as their application to the therapy of erectile dysfunction.

Data sources  The data used in the present article were mainly from PubMed with relevant English articles published from 1974 to 2011. The search terms were “stem cells” and “erectile dysfunction”.

Study selection  Articles regarding the role of stem cells in erectile dysfunction and their application to the therapy of erectile dysfunction were selected.

Results  Stem cells hold great promise for regenerative medicine because of their ability to self-renew and to differentiate into various cell types. Meanwhile, in preclinical experiments, therapeutic gene-modified stem cells have been approved to offer a novel strategy for cell therapy and gene therapy of erectile dysfunction.

Conclusion  The transplantation of stem cells has the potential to provide cell types capable of restoring normal function after injury or degradation inerectile dysfunction. However, a series of problems, such as the safety of stem cells transplantation, their application in cell therapy and gene therapy of erectile dysfunction need further investigation.

     

Establishment and characterization of two new human embryonic stem cell lines, SYSU-1 and SYSU-2

Background Human embryonic stem cells can propagate indefinitely in vitro and are able to differentiate into derivatives of all three embryonic germ layers. The excitement surrounding human embryonic stem cells lies largely in their potential to produce specialized cells that can be used for transplant therapies. However, further investigation requires additional cell lines with varying genetic background. Therefore, efforts to derive and establish more human embryonic stern cell lines are highly warranted. Methods Surplus embryos （blastocysts） from donors were used to isolate the inner cell mass by immunosurgery. All cells were cultured continuously on irradiated murine embryonic fibroblasts feed layer and likely human embryonic stem cell colonies were subsequently characterized by cell surface marker staining, karyotyping and teratoma formation. Results Two human embryonic stern cell lines （SYSU-1 and SYSU-2） were established from surplus embryos. The two lines express several pluripotency markers including alkaline phosphatase, SSEA- 4, Tra-1-60, Oct-4, Nanog and Rex-1. They remain in undifferentiated state with normal karyotype after prolonged passages and can form embryoid bodies in vitro and teratoma in vivo. Conclusion Two new human embryonic stem cell lines have been established from surplus embryos. They can be used to understand selfrenewal and differentiating mechanisms and provide more choices for regenerative medicine.