Reticulum cells, stem cells and lymphocytes.
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Animals↗
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Neoformation of liver epithelial cells: progenitor cells, stem cells, and phenotypic transitions.
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2-Acetylaminofluorene↗
Primordial germ cells, stem cells and testicular cancer.
Primordial Germ Cells (PGCs) arise in the mouse embryo as a small population of cells some way from the gonad anlagen. In order for the embryo to develop into a fully fertile adult animal the PGCs must increase in number and reach the gonad. Mutations causing sterility in the mouse have identified some of the genes involved in regulating PGC development and some of these genes have been molecularly cloned. Similarly, mutations affecting the development and differentiation of PGC-derived tumors (teratomas and teratocarcinomas) have been identified in certain strains of mice and these identify genes involved in the normal growth and differentiation of PGCs. These studies should help to define the role of growth factors in PGC development and in the development of germ-cell-derived tumors.
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Stem cells. 'Stemness' genes still elusive.
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Animals↗
Tubular regeneration and the role of bone marrow cells: 'stem cell therapy'--a panacea?
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Animals↗
A comparison study in the proteomic signatures of multipotent germline stem cells, embryonic stem cells, and germline stem cells.
Germline stem (GS) cells can only differentiate into germline cells, while multipotent germ stem (mGS) cells, like embryonic stem (ES) cells, can differentiate into various somatic cells and tissues. The proteomic profiles in GS and mGS cells were compared by two-dimensional gel electrophoresis. Ten down-regulated and 16 up-regulated proteins were differentially expressed in mGS cells in comparison to GS cells, and these proteomic characteristics were very much similar to those in ES cells indicating that multipotency of mGS and ES cells is based on a common molecular event(s). Protein identification by mass spectrometry revealed that these proteins were functionally involved in cell signaling, transcription factors, metabolism, and protein folding. The identified proteins in the present study may thus reveal its biological characteristics and functional property in self-renewal and multipotency.
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Daily measurements of blood CD34+ cells after stem cell mobilization predict stem cell yield and posttransplant hematopoietic recovery.
The value of daily monitoring of the blood CD34+ cell concentration as a guide to the optimal timing of stem cell harvests was studied in 60 patients who underwent 66 stem cell mobilizations and 189 leukaphereses. There was a highly significant correlation between the blood CD34+ count and the CD34+ cell content in the apheresis product of the same day (r = 0.904, p < 0.01). Thus, the target yield of 4 x 10(6) CD34+ cells/kg can be harvested in one or two leukaphereses when the blood CD34+ cell count exceeds 50 x 10(6)/L. However, an insufficient harvest is to be expected when the blood CD34+ cell count is below 20 x 10(6)/L. The data from 35 autologous blood cell transplantations with a minimum CD34+ cell yield of 1.5 x 10(6)/kg showed that the recovery of blood neutrophil counts to 1.0 x 10(9)/L occurred in all patients within 9-14 days, but the time to recovery of the platelet counts to 20 x 10(9)/L may exceed 14 days, especially if the CD34+ cell content is below 4 x 10(6)/kg. Daily monitoring of blood CD34+ cell counts is a rapid and reliable means to guide the timing of stem cell collections. The count predicts well the CD34+ cell content of the harvests, the number of leukaphereses needed, and the speed of hematopoietic recovery.
Adult↗
Stem cells and stem cell transplantation.
Stem cell transplantation (SCT) is an increasingly used therapeutic approach for the treatment of hematological and non-hematological disease of neoplastic and non-neoplastic origin. How the phenomena controlling blood cell production take place during SCT is still largely unclear. Increasing knowledge of stem cell biology, the availability of large amounts of stem cells due to mobilization techniques, as well as new developments in hematopoietic cell manipulation offer exciting experimental and therapeutical options in the field of SCT and will be reviewed here.
Colony-Forming Units Assay↗
[Methodologies for isolation, expansion and differentiation of somatic stem cells(tissue stem cells)].
Recent studies have shown that pluriponten stem cells are also found in adult tissue. These adult stem cells has a great advantage over other stem cells sources, human embryos or human fetal tissue, that trouble many people on ethical grounds. While the adult stem cells have great potential for use in the cell therapy, we must pass numerous technical hurdles to reach a goal. Here we describe a subset of problems encountered in isolation and expansion of somatic stem cells for clinical application. As it is necessary to obtain the enough number of cells to supply the defect tissue and organ, we required purification and ex vivo expansion of stem cells, overcoming senescence. We also refer to the argument about plasticity of adult stem cells.
Adult↗
[A stem cell ... is stem cell?].
We are used to associate stem cells with renewable tissues such as blood, gut and skin. But some cells in the adult central nervous system have the capacity to generate new neurons and glial cells as well and as such, they are considered to be neural stem cell. Yet their ability to generate neurons and glia, and their presence in the central nervous system throughout life, suggests new, intriguing possibilities for recovery and repair after damage to the central nervous system--and unexpectedly, the regeneration of blood tissues. After transplantation into irradiated hosts, neural stem cells were found to produce a variety of blood cell types including myeloid and lymphoid cells as well as early hematopoietic cells. Therefore, the developmental potential of stem cells is not restricted to the differentiated elements of the tissue in which they reside. Multipotential stem cells can persist in an undifferentiated state, and depending on specific environmental conditions function as a stem cell for many different tissues.
Hematopoietic Stem Cells↗
Maintenance of pluripotential embryonic stem cells by stem cell selection.
As gastrulation proceeds, pluripotential stem cells with the capacity to contribute to all primary germ layers disappear from the mammalian embryo. The extinction of pluripotency also occurs during the formation of embryoid bodies from embryonic stem (ES) cells. In this report we show that if the initial differentiated progeny are removed from ES cell aggregates, further differentiation does not proceed and the stem cell population persists and expands. Significantly, the presence of even minor populations of differentiated cells lead to the complete loss of stem cells from the cultures. This finding implies that the normal elimination of pluripotent cells is dictated by inductive signals provided by differentiated progeny. We have exploited this observation to develop a strategy for the isolation of pluripotential cells. This approach, termed stem cell selection, may have widespread applicability to the derivation and propagation of stem cells.
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Cancer stem cells--normal stem cells "Jedi" that went over to the "dark side".
Evidence has accumulated that cancer develops from a population of quiescent tissue committed/pluripotent stem cells (TCSC/PSC) or cells developmentally closely related to them that are distributed in various organs. To support this notion, stem cells (SC) are long lived cells and thus may become the subject of accumulating mutations that are crucial for initiation/progression of cancer. More important, they may maintain these mutations and pass them to the daughter stem cells. Therefore, mutations that occur in normal SC, accumulate during the life of an organism at the clonal level in the stem cell compartment committed to a given tissue/organ. As a consequence, this may lead to the malignant transformation of SC and tumor initiation. Furthermore, many biological features of normal and cancer SC such as the physiological trafficking of normal and metastasis of cancer stem cells involve similar molecular mechanisms, and we discuss these similarities here. Therefore, looking both at the origin and behavioral aspects we can envision cancer SC being normal SC "Jedi" that went over to the "dark side".
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Relationships between stem cells and cancer stem cells.
Stem cells have been shown to exist in a variety of tissues. Recent studies have characterized stem cell gene expression patterns, phenotypes, and potential therapeutic uses. One of the most important properties of stem cells is that of self renewal. This raises the possibility that some of the clinical properties of human tumors may be due to transformed stem cells. Similar signaling pathways may regulate self renewal in normal and transformed stem cells. These rare transformed stem cells may drive the process of tumorigenesis due to their potential for self renewal. There are important ramifications for clinical cancer treatment if the growth of solid tumors is at least partially dependent on a cancer stem cell population. In the cancer stem cell model, tumor recurrence may be due to the non-targeted stem cell compartment repopulating the tumor. If cancer stem cells can be prospectively identified and isolated, it should be possible to identify therapies that will selectively target these cells.
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Pluripotential liver stem cells: facultative stem cells located in the biliary tree.
The ability of the liver to regenerate after parenchymal damage is usually accomplished by the ephemeral entry of normally proliferatively quiescent (G0) hepatocytes into the cell cycle. However, when hepatocyte regeneration is defective, arborizing ductules which are continuous with the biliary tree, proliferate and migrate into the surrounding parenchyma. In man these biliary cells have variously been referred to as ductular structures, neoductules and neocholangioles, and have been observed in many forms of chronic liver disease, including cancer. In experimental animals similar ductal cells are usually called oval cells, and their association with defective regeneration has led to the belief that these cells represent a progenitor cell population. Oval cells are thought to take over the burden of regenerative growth after substantial hepatocyte loss, suggesting that they are the progeny of facultative stem cells. The liver is not, however, generally considered as a stem cell-fed hierarchy, although this is disputed by others. Despite this, the subject of oval cells has aroused intense interest as these cells may represent a target population for hepatic carcinogens, and they may be useful vehicles for ex vivo gene therapy. This review proposes that the liver does harbour stem cells which are located throughout the biliary epithelium, and that oval cells represent the progeny of these stem cells and function as an amplification compartment for the generation of 'new' hepatocytes. This is a conditional process which only occurs when the regenerative capacity of hepatocytes is overwhelmed and thus, unlike the intestinal epithelium, the liver is not behaving as a classical continually renewing stem cell-fed lineage. We focus on the biliary network, not merely as a conduit for bile, but also as a cell compartment with the potential to proliferate under appropriate conditions and give rise to fully differentiated hepatocytes and other cell types.
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Hematopoietic stem cells, leukemic stem cells and chronic myelogenous leukemia.
Blood-related cancers, or leukemias, have been shown to arise from a rare subset of cells that escape normal regulation and drive the formation and growth of the tumor. The finding that these so-called cancer stem cells, or leukemic stem cells (LSC), can be purified away from the other cells in the tumor allows their precise analysis to identify candidate molecules and regulatory pathways that play a role in progression, maintenance, and spreading of leukemias. The analyses of the other, numerically dominant, cells in the tumor, while also interesting, do not directly interrogate these key properties of malignancies. Mouse models of human myeloproliferative disorder and acute myelogenous leukemia have highlighted the remarkable conservation of disease mechanisms between both species. They can now be used to identify the LSC for each type of human leukemia and understand how they escape normal regulation and become malignant. Given the clinical importance of LSC identification, the insights gained through these approaches will quickly translate into clinical applications and lead to improved treatments for human leukemias.
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Mesenchymal stem cells in stem cell transplant recipients are damaged and remain of host origin.
The aim of this study was to investigate the expansion capacity and origin of bone marrow-derived mesenchymal stem cells (MSCs) in 34 patients who received a sex-mismatched stem cell transplant (SCT). Polymerase chain reaction (PCR) analysis of the amelogenin gene (AMEL) was used to detect donor-derived MSCs. Cultured MSCs were hybridized with fluorescence in situ hybridization (FISH) probes for chromosomes X and Y to distinguish cells of donor origin from those of host origin. The MSCs of 31 of the 34 patients showed confluent stroma, and the MSCs from 24 of these 31 patients were successfully passaged more than 5 times and were able to be used for PCR and FISH analyses. The colony-forming unit-fibroblast, confluence time, and passage numbers of the MSCs and the colony-forming capacity of the hematopoietic progenitor cells of the patients were significantly different from those of 30 healthy control subjects. Flow cytometry results showed that the proportion of CD14(+)CD45(+) cells, which are regarded as monocytes/macrophages, in cultured MSCs (fifth passage) was less than 0.04%. PCR and FISH analyses revealed that the MSC-derived cells in all 24 patients were from the host. In conclusion, the expansion capacity of MSCs in patients who receive an SCT is damaged, and the MSCs originate from the host.
Adolescent↗
Tumor stem cells.
Stem cells possess two basic characteristics: they are able to renew themselves and to develop into different cell types. The link between normal stem cells and tumor cells could be examined in three aspects: what are the differences and similarities in the control of self-renewal capacity between stem cells and tumor cells; whether tumor cells arise from stem cells; do tumorous stem cells exist? Since tumor cells also exhibit self-renewal capacity, it seems plausible that their regulation is similar to that of the stem cells. The infinite self-renewal ability (immortalization) is assured by several, so far only partly known, mechanisms. One of these is telomerase activity, another important regulatory step for survival is the inhibition of apoptosis. Other signal transduction pathways in stem cell regulation may also play certain roles in carcinogenesis: e.g. Notch, Sonic hedgehog (SHH), and Wnt signals. Existence of tumor stem cells was suggested since it is simpler to retain the self-renewal capacity than to reactivate the immortality program in an already differentiated cell. Moreover, stem cells live much longer than the differentiated ones, and so they are exposed for a long period of time to impairments, collecting gene errors leading to the breakdown of the regulation. However, it is still an open question whether all cells in the tumor possess the capacity that produces this tissue or not, that is: are there tumor stem cells or there are not. If tumor stem cells exist, they would be the main target for therapy: only these must be killed since the other tumor cells possess limited proliferative capacity, therefore limited life span. The only problem is that during tumor progression stem-like cells can develop continuously and the identification but mainly the prevention of their formation is still a great challenge.
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Changing genetic world of IVF, stem cells and PGD. B. Polarities and gene expression in differentiating embryo cells and stem cells.
Novel genetic techniques in the later twentieth century led to new analytical methods for assessing the growth of embryos and stem cells and improve preimplantation diagnosis. Increasing attention to the nature of polarities in mouse and human embryos revealed the existence of an animal-vegetal axis in human oocytes and embryos. Combinations of meridional and transverse cleavage divisions, the latter due to spindle rotation, determined the unequal division of ooplasm to embryonic blastomeres. Blastomeres with differing functions were accordingly formed in 4-cell embryos, including founders of inner cell mass and trophectoderm. New forms of gene analysis led to the polymerase chain reaction, while fluorescence in-situ hybridization revealed astonishingly high degrees of heteroploidy in human embryos. Developmental genetics gained immense analytical power as cDNA libraries, microarrays, transcriptomes RNAi and other methods clarified the roles of hundreds of genes in pre- and early post-implantation embryos and stem cells.
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