Endothelial progenitor cells from human fetal aorta cure diabetic foot in a rat model.

OBJECTIVE: Recent evidence has suggested that circulating endothelial progenitor cells (EPCs) can repair the arterial endothelium during vascular injury. However, a reliable source of human EPCs is needed for therapeutic applications. In this study, we isolated human fetal aorta (HFA)-derived EPCs and analyzed the capacity of EPCs to differentiate into endothelial cells. In addition, because microvascular dysfunction is considered to be the major cause of diabetic foot (DF), we investigated whether transplantation of HFA-derived EPCs could treat DF in a rat model. METHODS: EPCs were isolated from clinically aborted fetal aorta. RT-PCR, fluorescence-activated cell sorting, immunofluorescence, and an enzyme-linked immunosorbent assay were used to examine the expressions of CD133, CD34, CD31, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), von Willebrand Factor (vWF), and Endothelial Leukocyte Adhesion Molecule-1 (ELAM-1). Morphology and Dil-uptake were used to assess function of the EPCs. We then established a DF model by injecting microcarriers into the hind-limb arteries of Goto-Kakizaki rats and then transplanting the cultured EPCs into the ischemic hind limbs. Thermal infrared imaging, oxygen saturation apparatus, and laser Doppler perfusion imaging were used to monitor the progression of the disease. Immunohistochemistry was performed to examine the microvascular tissue formed by HFA-derived EPCs. RESULTS: We found that CD133, CD34, and VEGFR2 were expressed by HFA-derived EPCs. After VEGF induction, CD133 expression was significantly decreased, but expression levels of vWF and ELAM-1 were markedly increased. Furthermore, tube formation and Dil-uptake were improved after VEGF induction. These observations suggest that EPCs could differentiate into endothelial cells. In the DF model, temperature, blood flow, and oxygen saturation were reduced but recovered to a nearly normal level following injection of the EPCs in the hind limb. Ischemic symptoms also improved. Injected EPCs were preferentially and durably engrafted into the blood vessels. In addition, anti-human CD31+-AMA+-vWF+ microvasculars were detected after transplantation of EPCs. CONCLUSION: Early fetal aorta-derived EPCs possess strong self-renewal ability and can differentiate into endothelial cells. We demonstrated for the first time that transplanting HFA-derived EPCs could ameliorate DF prognosis in a rat model. These findings suggest that the transplantation of HFA-derived EPCs could serve as an innovative therapeutic strategy for managing DF.

Isolation and culture of human oligodendrocyte precursor cells from neurospheres.

Culture of human oligodendrocyte precursor cells (OPCs) can help understand the regulatory mechanism of differentiation and myelination of oligodendrocytes. However, existing culture methods have limitations, particularly the lack of a source of human donor tissue and high cost. We sorted cells with the A2B5(+)PSA-NCAM(-) phenotype from neurospheres instead of human donor tissues through immunomagnetic sorting and subsequently cultured the isolated cells in OPC medium. Of all the isolated cells, 15.69% were of the A2B5(+)PSA-NCAM(-) phenotype. More than 90% of the isolated OPCs expressed the OPC-specific markers O4, PDGFαR, and Sox10, and less than 5% of cells expressed GFAP and Tuj-1. After induction, the isolated cells had the capacity to differentiate into oligodendrocytes. Furthermore, the OPCs could be stably passaged in vitro for at least four generations and all the cells had high expression levels of O4 and Sox10 and very low expression levels of GFAP and Tuj-1; moreover, the cells had the capacity to differentiate into oligodendrocytes. After four passages, OPCs can proliferate at least 14 times above. In addition, in the presence of B27, only one cytokine, namely, bFGF, was sufficient to maintain proliferation, and this greatly reduced the experimental cost. Cells of the A2B5(+)PSA-NCAM(-) phenotype have already been identified as OPCs. We developed and characterized a reproducible, simple, and economical method for the isolation and culture of human OPCs. This method will contribute to studying the function of OPCs in development, disease, and treatment.

Immortalization and characterization of human dental mesenchymal cells.

OBJECTIVES: Due to the rarity of human embryonic samples and limited proliferating capability of primary human dental mesenchymal cells, it is valuable to create an immortalized human dental mesenchymal cell line for studying dental mesenchymal cell differentiation and signalling pathways during dentinogenesis in humans. METHODS: In this study, dental mesenchymal cells from human molar tooth germs at 19-week gestation were isolated and immortalized with pSV40. Single cell colonies were then selected by 96-well plate dilution. The immortalized cell line was characterized using immunofluorescent microscopy, RT-PCR and Western blot for the expression of SV40 large T antigen and five genes specific for the mesenchymal stage during tooth development. The differentiation and mineralization activities of the immortalized and primary cells were compared using adipogenic and calcifying induction. RESULTS: The immortalized dental mesenchymal cell line displayed a higher proliferation rate, expressed several tooth-specific markers including Msx1, Pax9, Lhx6, Barx1, and Runx2, and maintained the ability to differentiate and form mineralized nodules. CONCLUSIONS: Our results demonstrated that the immortalized human mesenchymal cell line retained the characteristics similar to primary human dental mesenchymal cells and can be used for studying the mechanisms of human dental mesenchymal cell differentiation and signalling pathways involved in human odontogenesis.

NRIP1/RIP140 siRNA-mediated attenuation counteracts mitochondrial dysfunction in Down syndrome.

Mitochondrial dysfunction, which is consistently observed in Down syndrome (DS) cells and tissues, might contribute to the severity of the DS phenotype. Our recent studies on DS fetal hearts and fibroblasts have suggested that one of the possible causes of mitochondrial dysfunction is the downregulation of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α or PPARGC1A)--a key modulator of mitochondrial function--and of several nuclear-encoded mitochondrial genes (NEMGs). Re-analysis of publicly available expression data related to manipulation of chromosome 21 (Hsa21) genes suggested the nuclear receptor interacting protein 1 (NRIP1 or RIP140) as a good candidate Hsa21 gene for NEMG downregulation. Indeed, NRIP1 is known to affect oxidative metabolism and mitochondrial biogenesis by negatively controlling mitochondrial pathways regulated by PGC-1α. To establish whether NRIP1 overexpression in DS downregulates both PGC-1α and NEMGs, thereby causing mitochondrial dysfunction, we used siRNAs to decrease NRIP1 expression in trisomic human fetal fibroblasts. Levels of PGC-1α and NEMGs were increased and mitochondrial function was restored, as shown by reactive oxygen species decrease, adenosine 5'-triphosphate (ATP) production and mitochondrial activity increase. These findings indicate that the Hsa21 gene NRIP1 contributes to the mitochondrial dysfunction observed in DS. Furthermore, they suggest that the NRIP1-PGC-1α axe might represent a potential therapeutic target for restoring altered mitochondrial function in DS.

MicroRNAs function primarily in the pathogenesis of human anencephaly via the mitogen-activated protein kinase signaling pathway.

Anencephaly is one of the most serious forms of neural tube defects (NTDs), a group of congenital central nervous system (CNS) malformations. MicroRNAs (miRNAs) are involved in diverse biological processes via the post-transcriptional regulation of target mRNAs. Although miRNAs play important roles in the development of mammalian CNS, their function in human NTDs remains unknown. Using a miRNA microarray, we identified a unique expression profile in fetal anencephalic brain tissues, characterized by 70 upregulated miRNAs (ratio ≥ 2) and 7 downregulated miRNAs (ratio ≤ 0.5) compared with healthy human samples. Ten miRNAs with altered expression were selected from the microarray findings for validation with real-time quantitative reverse transcription-polymerase chain reaction. We found that in anencephalic tissues, miR-22, miR-23a, miR-34a, miR-103, miR-125a, miR-132, miR-134, miR-138, and miR-185 were significantly upregulated, while miR-149 was significantly downregulated. Furthermore, 459 potential target genes within the validated miRNAs were revealed using combined four target prediction algorithms in the human genome, and subsequently analyzed with the Molecule Annotation System 3.0. A total of 119 target genes were ultimately identified, including those involved in 22 singular annotations (i.e., transcription, signal transduction, and cell cycle) and 55 functional pathways [i.e., mitogen-activated protein kinase (MAPK) signaling pathway, and actin cytoskeleton regulation]. Six target genes (HNRPU, JAG1, FMR1, EGR3, RUNX1T1, and NDEL1) were chosen as candidate genes and associated with congenital birth abnormalities of the brain structure. Our results, therefore, suggest that miRNA maladjustment mainly contributes to the etiopathogenesis of anencephaly via the MAPK signaling pathway.

Fetal mesenchymal stromal cells differentiating towards chondrocytes acquire a gene expression profile resembling human growth plate cartilage.

We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs) differentiating towards chondrocytes as an alternative model for the human growth plate (GP). Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFß3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development.

Human mesenchymal stem cells derived from limb bud can differentiate into all three embryonic germ layers lineages.

Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them "human limb bud-derived mesenchymal stem cells" (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro.

Valproic acid induces apoptosis in differentiating hippocampal neurons by the release of tumor necrosis factor-α from activated astrocytes.

Human studies of neurodevelopment suggest that children exposed in utero to certain antiepileptic drugs (AEDs) suffer a variety of brain-behavior sequelae, such as neural tube defects, developmental delays, cognitive deficits, etc. Valproic acid (VPA), a commonly used AED, has greater risk for these side effects compared with other AEDs. However, the detailed molecular mechanisms underlying this developmental neurotoxicity of VPA is unclear despite previous research demonstrating that VPA could induce widespread apoptotic neurodegeneration in developing brains of animal models. This study characterizes the role of astrocytes in VPA-induced neurodegeneration. In developing brains, we evaluated the developmental neurotoxicity of VPA on differentiating neurons and astrocytes from neural progenitor cells cultured from the hippocampus of human fetuses. Exposure of a neuron-enriched culture to VPA at 250µM or 500µM did not cause neuronal apoptosis, but at 1mM and 7 days exposure, a slight increase in the percentage of apoptotic cells was observed. In contrast, VPA at 250µM to 1mM, selectively induced neuronal apoptosis in a neuron-astrocyte mixed cell culture model. The VPA-treated astrocytes showed morphological changes, and the level of tumor necrosis factor-α (TNF-α) was elevated in the supernatant. Both neuronal apoptosis and TNF-α release from astrocytes increased with concentration and exposure time to VPA, suggesting a synergism between the two cell types. Treatment of the neuron-astrocyte mixed culture exposed to VPA with TNF-α antibody partly prevented neuronal apoptosis, while the addition of exogenous TNF-α induced apoptosis in both cultures. Moreover, this pro-apoptotic effect was specific to VPA, as another AED, valpromide, failed to mimic this pro-apoptotic effect, nor did an inhibitor of histone deacetylase (iHDAC), sodium butyrate (NaB). We report a novel finding that astrocytes participate in VPA induced neurodegeneration by releasing TNF-α.

[Differentiation of dofaminergic neurons from the human embryonal nerve cells in culture].

The aim of our experiments was to determine the dofaminergic differentiation potential of human embryonic nerve tissue in culture to obtain cell material for neurotransplantation enriched with determinative dofaminergic cells precursors. During the period of culturing their amount in the experimental samples reliable increased from 5.6 +/- 4.3% dofaminergic neurons cells in the field of vision to 23.5 +/- 2.6%. At the same time in the control samples their concentration was 8.1 +/- 6.5% cells in the field of vision. Dofaminergic differentiation was confirmed by expression analyses of genes associated with this type of neuronal differentiation. We have demonstrated that during the period of culture expression of early transcription factors--Nurr1 and Lmx1b disappears while TH expression level increases. So, using specific culture condition the cell material for neurotransplantation enriched by dofaminergic neuron precursors can be obtained.

Characterization of mesenchymal stem cells (MSCs) from human fetal lung: potential differentiation of germ cells.

Pluripotent mesenchymal stem-like cell lines were established from lungs of 3-4 months old aborted fetus. The cells present the high ex vivo expansion potential of MSC, a typical fibroblast-like morphology and proliferate up to 15 passages without displaying clear changes in morphology. Immunological localization and flow cytometry analyses showed that these cells are positive for OCT4, c-Kit, CD11, CD29, CD44, telomerase, CD106, CD105, CD166, and SSEA1, weakly expression or negative for SSEA1, SSEA3, SSEA4, CD34, CD105 and CD106. These cells can give rise to the adipogenic as evidenced by accumulation of lipid-rich vacuoles within cells identified by Oil-red O when they were induced with 0.5 mM isobutylmethylxanthine, 200 microM indomethacin, 10(-6)M dexamethasone, and 10 microg/ml of insulin in high-glucose DMEM. Osteogenic lineage cells were generated in 0.1 microM dexamethasone, 50 microg/ml ascorbic acid, 10 mM beta-glycerophosphate, which are shaped as the osteoblastic morphology, expression of alkaline phosphatase (AP), and the formation of a mineralized extracellular matrix identified by Alizarin Red staining. Neural cells are observed when the cultures were induced with 2-mercapometal, which are positive for nestin, NF-100, MBP and GFAP. Additionally, embryoid bodies (EBs) and sperm like cells are obtained in vitro differentiation of these lung MSCs induced with 10(-5)M retinoic acid (RA). These results demonstrated that these MSCs are pluripotent and may provide an in vitro model to study germ-cell formation and also as a potential source of sperms for male infertility.

Flow perfusion culture of human fetal bone cells in large beta-tricalcium phosphate scaffold with controlled architecture.

One unsolved problem in bone tissue engineering is how to enable the survival and proliferation of osteoblastic cells in large scaffolds. In this work, large beta-tricalcium phosphate scaffolds with tightly controlled channel architectures were fabricated and a custom-designed perfusion bioreactor was developed. Human fetal bone cells in third passage were seeded onto the scaffolds and cultured in static or flow perfusion conditions for up to 16 days. Compared with nonperfused constructs, flow perfused constructs demonstrated improved cells proliferation and differentiation according to cell viability, glucose consumption, alkaline phosphatase activity, and osteopontin. Moreover, after 16 days of perfusion culture, a homogenous layer composed of cells and mineralized matrix throughout the whole scaffold was observed by scanning electron microscopy and histological study. In contrast, cells were located only along the scaffold perimeter in static culture. These results demonstrated the feasibility and benefit of perfusion culture in conjunction with well-defined three-dimensional environment for large bone graft construction. Porous scaffold with controlled architecture can be a potential tool to evaluate the effects of scaffold specific geometry on fluid flow configuration and cell behavior under perfusion culture.

Differential immunomodulatory effects of fetal versus maternal multipotent stromal cells.

Protective mechanisms are likely to be present at the fetomaternal interface because fetus-specific alloreactive T cells present in the decidua do not harm the fetus. We tested the immunosuppressive capacity of maternal and fetal multipotent stromal cells (MSC). Single cell suspensions were made from second-trimester amnion, amniotic fluid, and decidua. Culture-expanded cells were identified as MSC based on phenotype and multilineage potential. Coculture of MSC in a primary mixed lymphocyte culture of unrelated responder-stimulator combinations resulted in a dose-dependent inhibition of proliferation. Fetal MSC demonstrated a significantly higher inhibition compared with maternal MSC. This stronger inhibition by fetal MSC was even more prominent in a secondary mixed lymphocyte reaction (MLR) with primed alloreactive T cells. Analysis of cytokine production revealed that fetal MSC produced significantly more interleukin (IL)-10 and vascular endothelial growth factor than maternal MSC. Cell-cell contact is needed for part of the inhibitory effects of MSC. In addition, soluble factors play a role because blocking experiments with anti-IL-10 revealed that the inhibition of the MLR response by fetal MSC is mainly mediated by IL-10. For maternal MSC, other soluble factors seem to be involved. Fetal MSC derived from the fetomaternal interface have a stronger inhibitory effect on naive and antigen-experienced T cells compared with maternal MSC, which is probably related to their higher IL-10 production.

[Vaccines, biotechnology and their connection with induced abortion]. / Vacunas, Biotecnología y su Relación con el Aborto Provocado.

Diploid cells (WI-38, MRC-5) vaccines have their origin in induced abortions. Among these vaccines we fi nd the following: rubella, measles, mumps, rabies, polio, smallpox, hepatitis A, chickenpox, and herpes zoster. Nowadays, other abortion tainted vaccines cultivated on transformed cells (293, PER.C6) are in the pipeline: flu, Respiratory Syncytial and parainfluenza viruses, HIV, West Nile virus, Ebola, Marburg and Lassa, hepatitis B and C, foot and mouth disease, Japanese encephalitis, dengue, tuberculosis, anthrax, plague, tetanus and malaria. The same method is used for the production of monoclonal antibodies and other proteins, gene therapy and genomics. Technology enables us to develop the aforementioned products without resorting to induced abortion. Full disclosure of the cell origin in the labelling of vaccines and other products must be supported. There are vaccines from non-objectionable sources which should be made available to the public. When no alternative vaccines exist, ethical research must be promoted. Non-objectionable sources in the production of monoclonal antibodies, gene therapy and genomics must be encouraged. It is not be consistent to abstain from products originated in embryonic stem cells and at the same time approve of products obtained from induced abortions. It is of paramount importance to avoid that induced abortion technology seeps into every field of Medicine.

[Quantification of type I and III collagen content in normal human skin in different age groups].

OBJECTIVE: To quantify the content of type I, III collagen and their ratio in normal human skin of different age, and to explore the regulation of changes. METHODS: The normal human skin specimens were obtained from 6 spontaneously aborted fetus and 56 burn patients of different ages, including infants (newborn -3 years), pre-school group ( > 3, < or =7 years), adolescent group ( >7, < or = 18 years), youth and middle age group ( > 18, < or = 50 years), and elderly group ( > 50 years), were studied. The total collagen content were determined by hydroxyproline method. The contents of type I, Ill collagen and their ratio were examined by immunohistochemistry. RESULTS: The total collagen content decreased along with increase in age, and it was highest in fetus [(543 +/- 13) microg/g]. The ratio between type I and Ill collagen increased along with increase in age. The content of type III collagen was highest in fetus [(278 +/- 7) microg/g], and it decreased along with increase in age. The content of type I collagen content was [(265 +/- 7) microg/g] in fetus, and it was increased slightly in infant and pre-school groups, then decreased along with advance in age. CONCLUSION: Decomposition of type III collagen in normal human skin may exceed its synthesis after birth immediately, leading to its reduction. Synthesis of type I collagen in normal human skin is dominant before 8 years old, and it shows an opposite tendency afterwards.

Isolation, characterization and gene modification of fetal neural stem/progenitor cells from cynomolgus monkey.

Successful isolation and expansion of neural stem/progenitor cells from cynomolgus monkey (cm-NSPCs), may not only help to increase our understanding of NSPCs, but also provide an important translational tool for preclinical trials. Here we initially isolated NSPCs from aborted fetal cynomolgus monkey brain, and expanded them in adherent culture system. Then we demonstrated that cultured cm-NSPCs were almost bipolar cells proliferated in clump-like structure, expressed typical markers for NSPCs, and could differentiate into neurons, astrocytes, and oligodendrocytes. After transduction with lentivirus, 70-80% of cm-NSPCs expressed enhanced green fluorescent protein and the stemness was unaffected. This study provided basis for obtaining large numbers of cm-NSPCs, and efficient transduction of them with exogenous genes, which would facilitate cell-based therapies in nonhuman primate models, and might help to investigate the mechanism of central nervous system development and/or controlling neural regeneration.

[Isolation and differentiation characteristics of dermal multipotent stem cells from humans of different ages cultured in vitro].

OBJECTIVE: To study isolation, identification and differentiation characteristics of dermal multipotent stem cells from human of different age in vitro culture. METHODS: Skin samples( 1 cm x 1 cm) were harvested from fetus, infant, adult and elderly. The original clones were screened in stem cell medium. The diameter and number of clones were recorded. Analysis of each clone and determination of the expression of various related proteins were carried out. RESULTS: The number of suspended clones from normal skins of fetus, infant, adult and the elderly were (20. 1 +/-2. 5) x 102 , (15. 8 +/-5. 7) x 102, (10. 8 +/-1.3) x 10(2), (6.2 +/- 1.4) x 10(2), respectively ( P <0.01), while the diameter of the clones from them were (83 +/-12) microm, (55 +/- 10) microm, (46 +/- 12) Lm, (42 +/-8) microm, respectively ( P <0.05). Cloned cells from fetus, infant, adult and elderly could differentiate into neuron cell , neuroglia cell, smooth muscle cell, and adipocyte. The clones from fetus were inclined to differentiate into neuron cells, but those from infant were inclined to differentiate into neuroglia cells, and those from adult and elderly were inclined to differentiate into adipocytes. After 1 month of culture, the clone forming rate of the cells from fetus, infant, adult and elderly were 41. 1% , 25.5% ,17.7% ,15.2% , respectively. The individual clone cells also showed ability of multidirectional differentiation. Nestin, fibronectin, c-Myc, STAT3 and hTERT protein were expressed in all clones. CONCLUSION: Multipotent stem cells with multi-direction differentiation and proliferation can be efficiently isolated from dermis of human of different age in stem cell culture medium. The number, proliferation and differentiation of dermal multipotent stem cells can be affected by age.

[Morphological research on brain development and expression of vital cytokines in brain of human 6-8 week old embryo aborted for unexpected cause].

OBJECTIVE: To clarify the changes in cell proliferation, differentiation, apoptosis and in the expression of vital cytokines during development of 6-8 week old embryo, and hence provide the evidence for identifying the mechanisms of cell proliferation, differentiation, apoptosis during early developing human embryonic brain. METHODS: Human aborted embryos were obtained with the consents signed by the pregnant women with unexpected abortions in gestation of 6-8 weeks. The histochemical SABC method and TUNEL Staining were employed to this research project. RESULTS: At 6 weeks, two telencephalons, diencephalon, mesencephalon, metencephalon, and myelencephalon have been formed, and from week 6 to 8, every cerebral vesicle has had three layer cells including germinal layer (GL), intermediate layer ( IL ), and marginal zone (MZ). At 6-7 weeks, TUNEL-labeled cells and PCNA-, Bcl-2-, Bax-, Fas-, Fas-L-, Rb- and P53-positive cells were all observed in the GL and IL of the five brain regions, positive deposition appeared in nuclei. At week 8, Fas- and Rb-positive cells were observed in the IL of the five brain regions, positive deposition appeared in cytoplasm and cell processes, and no changes in the distributions of TUNEL-labeled cells and positive cells regarding the other five factors. The expressions of the cytokines were in agreement with the occurrence of the neuronal proliferation and apoptosis temporally and in space. CONCLUSION: During development in early embryo brain, neural precursor cell proliferation and apoptosis occur simultaneously. Fas, FasL and Bax may be involved in the induction of cell apoptosis. Bcl-2 probably prevents the cell apoptosis and provides a survival signal for cells. Rb and P53 may play a critical role in monitoring and maintaining the normal neural precursor cell to proliferation and differentiation.

Human embryonic stem cell research: an Australian perspective.

A conscience vote of individual parliamentarians in the Australian government last month regarding amendments to current legislation regulating human embryonic stem cell research yielded a surprising outcome. Despite opposition by the Australian Prime Minister, the Senate and House of Representatives voted to adopt the recommendations of the Lockhart Review and approve human somatic cell nuclear transfer, thus providing a consistent national policy for all researchers in Australia.