使用干细胞机制优化反向传播神经网络

借鉴细胞学中的干细胞理论,提出了基于干细胞机制的进化神经网络(SCEABPNN),以实现误差反向传播神经网络(BPNN)的优化。SCEABPNN不需要遗传神经网络(GABPNN)中的编码、解码、交叉、变异等操作,把网络中的结点看成细胞,通过细胞移植、细胞置换、细胞凋亡操作进行网络优化。仿真结果证实,SCEABPNN不但可以全局收敛,有效解决BPNN易陷局部最小的问题,而且收敛速度比GABPNN和标准BPNN更快。

间充质干细胞移植治疗作用机制

间充质干细胞治疗的疾病谱比造血干细胞更广。迄今为止,国外已有十多个间充质干细胞产品被批准临床应用,国内也有数个产品被批准临床试验研究。间充质干细胞通过直接和间接两种方式发挥治疗作用。直接方式包括归巢、促进外源干细胞植入患处,以及定向分化与多向分化等;间接方式包括双向调节免疫反应和炎症反应、抗氧化应激、抗纤维化、抗凋亡、造血支持作用及参与或促进血管再生、激活内源干细胞增殖分化及患病组织器官已分化的正常细胞去分化,以及抗衰老、抗瘢痕等。间充质干细胞移植治疗的作用机制十分复杂,迄今仍没有完全弄清,还需要进行深入研究。研究间充质干细胞的移植治疗作用机制,对于间充质干细胞临床应用具有重要意义。

造血干细胞的动员

引言 造血干细胞(HSC)移植的潜在优点包括避免骨髓的穿刺和麻醉,能扩大适宜病人群,包括那些骨髓已被肿瘤罹患或先前骨盆接受放射疗法的病人,这些常妨碍骨髓采集.

细胞“返老还童”二维码被破译

生命科学中是否存在类似支付二维码一样的二进制规律密码？中国科学院广州生物医药与健康研究院裴端卿课题组通过研究干细胞诱导过程,发现细胞在发生＂返老还童＂时,染色质的＂开—关＂状态恰似二维码一样记录了这个过程的大量信息。通过破译这些＂二维码＂的内在含义,他们阐述了干细胞诱导过程的变化机制。成纤维细胞在导入诱导因子后,会启动一套奇妙的未知程序,将体细胞返老还童到受精后约3.5天的状态。

Stem cells, a two-edged sword: Risks and potentials of regenerative medicine

The recent advancements in stem cell (SC) biology have led to the concept of regenerative medicine, which is based on the potential of SC for therapies aimed to facilitate the repair of degenerating or injured tissues. Nonetheless, prior to large scale clinical appli- cations, critical aspects need to be further addressed, including the long-term safety, tolerability, and efficacy of SC-based treatments. Most problematic among the risks of SC-based therapies, in addition to the pos- sible rejection or loss of function of the infused cells, is their potential neoplastic transformation. Indeed, SCs may be used to cure devastating diseases, but their specific properties of self-renewal and clonogenicity may render them prone to generate cancers. In this respect, ‘Stemness’ might be seen as a two-edged sword, its bright side being represented by normal SCs, its dark side by cancer SCs. A better understand- ing of SC biology will help fulfill the promise of regen- erative medicine aimed at curing human pathologies and fighting cancer from its roots.

Local signals in stem cell-based bone marrow regeneration

The cellular basis of bone marrow （BM） tissue development and regeneration is mediated through hematopoietic stem cells （HSCs） and mesenchymal stem cells （MSCs）. Local interplays between hematopoietic cells and BM stromal cells （BMSCs） determine the reconstitution of hematopoiesis after myelosuppression. Here we review the BM local signals in control of BM regeneration after insults. Hematopoietic growth factors （HGFs） and cytokines produced by BMSCs are primary factors in regulation ofBM hematopoiesis. Morphogens which are critical to early embryo development in multiple species have been added to the family of HSCs regulators, including families of Wnt proteins, Notch ligands, BMPs, and Hedgehogs. Global gene expression analysis of HSCs and BMSCs has begun to reveal signature groups of genes for both cell types. More importantly, analysis of global gene expression coupled with biochemical and biological studies of local signals during BM regeneration have strongly suggested that HGFs and cytokines may not be the primary local regulators for BM recovery, rather chemokines （SDF- 1, FGF-4） and angiogenic growth factors （VEGF-A, Ang- 1） play instructive roles in BM reconstitution after myelosuppression. A new direction of management of BM toxicity is emerging from the identification of BM regenerative regulators.

ABC transporters,neural stem cells and neurogenesis - a different perspective

Stem cells intrigue. They have the ability to divide exponentially, recreate the stem cell compartment, as well as create differentiated cells to generate tissues. Therefore, they should be natural candidates to provide a renewable source of cells for transplantation applied in regenerative medicine. Stem cells have the capacity to generate specific tissues or even whole organs like the blood, heart, or bones. A subgroup of stem cells, the neural stem cells （NSCs）, is characterized as a self-renewing population that generates neurons and glia of the developing brain. They can be isolated, genetically manipulated and differentiated in vitro and reintroduced into a developing, adult or a pathologically altered central nervous system. NSCs have been considered for use in cell replacement therapies in various neurodegenerative diseases such as Parkinson＇s disease and Alzheimer＇s disease. Characterization of genes with tightly controlled expression patterns during differentiation represents an approach to understanding the regulation of stem cell commitment. The regulation of stem cell biology by the ATP-binding cassette （ABC） transporters has emerged as an important new field of investigation. As a major focus of stem cell research is in the manipulation of cells to enable differentiation into a targeted cell population; in this review, we discuss recent literatures on ABC transporters and stem cells, and propose an integrated view on the role of the ABC transporters, especially ABCA2, ABCA3, ABCB 1 and ABCG2, in NSCs＇ proliferation, differentiation and regulation, along with comparisons to that in hematopoietic and other stem cells.

Generation of human/rat xenograft animal model for the study of human donor stem cell behaviors in vivo

AIM： TO accurately and realistically elucidate human stem cell behaviors in vivo and the fundamental mechanisms controlling human stem cell fates in vivo, which is urgently required in regenerative medicine and treatments for some human diseases, a surrogate human-rat chimera model was developed. METHODS： Human-rat chimeras were achieved by in utero transplanting low-density mononuclear cells from human umbilical cord blood into the fetal rats at 9-11 d of gestation, and subsequently, a variety of methods, including flow cytometry, PCR as well as immunohistochemical assay, were used to test the human donor contribution in the recipients. RESULTS： Of 29 live-born recipients, 19 had the presence of human CD45^＋ cells in peripheral blood （PB） detected by flow cytometry, while PCR analysis on genomic DNA from 11 different adult tissues showed that 14 selected from flow cytometry-positive 19 animals possessed of donor-derived human cell engraftment in multiple tissues （i.e. liver, spleen, thymus, heart, kidney, blood, lung, muscle, gut and skin） examined at the time of tissue collection, as confirmed by detecting human 132- microglobulin expression using immunohistochemistry. Tn this xenogeneic system, the engrafted donor-derived human cells persisted in multiple tissues for at least 6 mo after birth. Moreover, transplanted human donor cells underwent site-specific differentiation into CK18-positive human cells in chimeric liver and CEHS-positive human cells in chimeric spleen and thymus of recipients. CONCLUSION： Taken together, these findings suggest that we successfully developed human-rat chimeras, in which xenogeneic human cells exist up to 6 mo later. This humanized small animal model, which offers an in vivo environment more closely resembling to the situations in human, provides an invaluable and effective approach for in vivo investigating human stem cell behaviors, and further in vivo examining fundamental mechanisms controlling human stem cell fates in the future. The potential for new advances in our better understanding the living biological systems in human provided by investigators in humanized animals will remain promising.

Mechanism of RNA interference targeting at survivin gene on apoptosis of hepatoma-cellular carcinoma cell line HepG2

Objective:The aim of this study was to investigate the molecular mechanism of anti-apoptotic action of survivin to the hepatoma-cellular carcinoma cell line HepG2.Methods:Design and synthesize siRNA gene sequence specifically targeting at HepG2 cell.HepG2 cells cultures were divided into five groups:blank control group,negative control group,low dose group,medium dose group and high dose group.HepG2 cells were treated respectively by pshRNA-survivin-387 of different concentrations.The apoptosis index(AI) was determined by flow cytometry(FCM).Cells were stained with rhodomine-123(Rh123) to detect changes of mitochondrial membrane potentials.The concentration of cytoplasmic cytochrome C(Cyt.C) was continuously determined by ELISA.Relative activities of caspase-9 and caspase-3 were assessed by colorimetric assay.Results:Compared with the control group,due to the function of short interference RNAs(SiRNAs) that suppresses the survivin gene expression,the apoptotic index of transfected groups were significantly higher than those of control groups(F = 13568.68,q = 110.47-327.16,P < 0.01),the apoptosis index of high concentration of transfected cells was higher than the low concentration transfected group(q = 39.63-168.22,P < 0.01).The apoptosis index of high concentrations transfected HepG2 cells was 25.54%,higher than that of blank control group,negative control group,low dose group and medium dose group(5.24%,6.61%,12.63% and 15.64%,respectively).HepG2 cells transfected with SiRNA exhibit gradually decreasing mitochondrial membrane potentials,which then lead to the releasing of Cyt C,following it were the activation of caspase-9 and caspase-3.Conclusion:Survivin performs the function of anti-apoptosis to the HepG2 cells via modulating the apoptosis of mitochondrial.HepG2 cells transfected with SiRNA survivin can significantly induce apoptosis.

High-efficiency somatic reprogramming induced by intact MII oocytes

Somatic nuclei can be reprogrammed into a pluripotent state by nuclear transfer, cell fusion and expression of transcription factors. However, these reprogramming processes are very inefficient, which has greatly hindered efforts to elucidate the underlying molecular mechanisms. Here, we report a new reprogramming strategy that combines the advantages of all three reprogramming methodologies into one process. We injected nuclei from cumulus cells into intact MII oocytes. Following activation, 80% of the reconstructed embryos developed to the blastocyst stage, and tetraploid （4N） embryonic stem （ES） cell lines were generated at a rate of 30% per reconstructed oocyte. We also generated triploid （3N） ES cells after injection of somatic nuclei into activated oocytes. 4N and 3N ES cells expressed pluripotent markers and differentiated into cell types of three embryonic germ layers in vivo. Moreover, all ES cells generated histocompatible, differentiated cells after being engrafted in immunocompetent B6D2F1 mice, showing that ES cells derived from this reprogramming strategy might serve as a source of genetically tailored tissues for transplantation. Thus, we have established a simple and highly efficient reprogramming procedure that provides a system for investigating the molecular mechanisms involved in somatic reprogramming.

Characterization of cancer stem-like cells in a novel STI571-resistant chronic myeloid leukemia cell line

Objective： To characterize a novel chronic myeloid leukemia （CML） cell line and to further elucidate the mechanisms of resistance to STI571. Methods： A novel K562 cell line （K562NP16） was achieved after exposure of the K562 cells to VP16. A small subpopulation （K562NP16 SP） that was capable of excluding Hoechst 33342 in the K562NP16 cell line was isolated by fiow cytometry sorting. The rest of the K562NP16 cells were classified as non-SP K562NP16. The mechanisms involved in K562NP16 SP cells which became resistant to STI571 were studied. Results： The levels of Bcr-Abl and Abl proteins were similar in the K562 cell line and in non-SP K562NP16 and K562NP16 SP cells. The multidrug-resistant gene 1 （MDR1） expression of the 170 kDa P-glycoprotein （P-gp） was detected in K562NP16 non-SP and K562NP16 SP cells but not in K562 cells. The expression levels of P-gp in the two K562NP16 cell lines were similar. Compared with non-SP K562/ VP16, the K562NP16 SP cells were more resistant to STI571. This resistance could hardly be reversed by many multidrug resistance inhibitors. In addition, in vivo study showed that the K562NP16 SP cells induced tumorigenesis in mice, while the K562NP16 non-SP cells failed to do so. Conclusion： A novel K562 cell line, K562NP16, was generated. A small side population K562NP16 SP cells, had high resistance to STI571 treatment and more tumorigenic than the K562 cells. It may represent the cancer stem cells of the K562NP16 cell line.

Progress in the treatment of myocardial infarction with stem cells transplantation

Embryonic stem cells and adult stem cells derives from bone marrow, muscule, liver, skin, nerve, adiposes and other tissues or organs are pluripotent. Embryonic stem cells in vitro can differentiate into derivatives of all three embryonic germ layers when transferred to an in vitro environment, and have the ability to form any fully differentiated cells of the body. A series of remarkable studies suggested that adult stem cells undergo novel patterns of development named as transdifferentiation. All of them can be induced into cardiomyocytes in a certain condition and used to treat myocardial infarction. In this review, progress in the treatment of myocardial infarction with stem cells transplantation is summarized.