Info

A The patient received myeloablative chemotherapy followed by infusion of HLA-matched allogeneic stem cells at 4.4 X 106 kg on d 9. The nadir of peripheral blood counts was reached on d 14-15. The patient experienced bleeding and fever on d 17 and was treated with platelets and antibiotics. Neutrophils appeared in the blood on d 20 she defervesced and was discharged on d 22. a The patient received myeloablative chemotherapy followed by infusion of HLA-matched allogeneic stem cells at 4.4 X 106...

Hematopoietic Stem Cells

With the now widely recognized plasticity of hematopoietic stem cells (HSCs), clearly indicating their ability to give rise to cell types of all three primordial germ cell layers (Anderson et al., 2001), the possibility that hepatic oval cells are actually derived from bone marrow-derived stem cells has introduced further speculation. In rodents, Petersen et al. (1999) first demonstrated that transplanted bone marrow stem cells traffic to the liver of animals lethally irradiated and whose...

Targeted Liver Injury In

Hepatotoxins can be valuable tools to amplify rare pathways of differentiation. Their major drawback is a lack of specificity that results in varying degrees of collateral damage, which can often Fig. 5. Hepatocytes in pancreas of rat maintained on CDE diet for 6 mo. Frozen liver section stained by indirect immunoperoxidase with MAb against OC.2, a cell-surface cytoplasmic antigen expressed on pancreatic ductal cells, oval cells, and bile duct epithelial cells. Split arrows show OC.2-positive...

And Barry R Stripp phd

Two levels of epithelial progenitors are involved in lung morphogenesis multipotent undifferentiated cells (lung primordial cells) and pluripotent regiospecific (bronchial, bronchiolar, and alveolar) stem cells. The trachea and bronchi are lined by pseudostratified columnar epithelium (ciliated, mucous and basal cells). The bronchioles are lined by simple columnar epithelium (ciliated and Clara cells). Pulmonary neuroendocrine cells (PNECs) are also present. The alveolar ducts and sacs and the...

X

D., Keighren, M. A., Flockhart, J. H., Innes, B. A., and Dorin, J. R. (1999) Murine submucosal glands are clonally derived and show a cystic fibrosis gene-dependent distribution pattern. Am. J. Respir. Cell Mol. Biol. 20 1181-1189. Borthwick, D. W., Shahbazian, M., Todd, K. Q., Dorin, J. R., and Randell, S. H. (2001) Evidence for stem-cell niches in the tracheal epithelium. Am. J. Respir. Cell Mol. Biol. 24 662-670. Boyden, E. A. (1972) Development of the human lung....

References

C., Hilton, K., Norris, M. L., and Surani, M. A. (1994) A functional analysis of imprinting in parthenogenetic embryonic stem cells. Development 120 1473-1482. Allen, N. D., Logan, K., Lally, G., Drage, D. J., Norris, M. L., and Keverne, E. B. (1995) Distribution of parthenogenetic cells in the mouse brain and their influence on brain development and behavior. Proc. Natl. Acad. Sci. USA 92 10,782-10,786. Bartolomei, M. S. and Tilghman, S. M. (1997) Genomic imprinting in...

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Seed and soil hypothesis, 21 Septum transversum, 346 Sertoli cells, 57, 65 Skin cancer, 289-306 melanoma, 297-306 non-melanoma, 289-296 Somatic differentiation of embryonic cells, 37 Sonic hedgehog, 210 Specific mouse embryonic antigen (SSEA), 35 Spectrosome, 59 Spermatogenesis, 59-64 cell signaling, 60-66 hormones and cytokines, 63 hub cells, 64 mammalian, 61, 62 Spermatogonia, 57-59 Spleen colonies (hematopoietic), 120 Spleen colonies (leukemic), 125 Spontaneous generation, 21 Squamous cell...

Blcf Ci

0 23456789 10 days of in vitro differentiation Fig. 2. In vivo vs in vitro hematopoietic development. To date, BL-CFCs have only been identified in vitro. Both BL-CFCs and primitive erythroid progenitors are transient. Definitive erythroid and myeloid lineages develop shortly after and persist throughout EB differentiation. Only the developmental kinetics, not the actual numbers, of each hematopoietic cell population is illustrated. The findings that BL-CFCs form blast colonies in response to...

On Characteristics Of Target Cells

A subpopulation of dark cells has been recognized within the infundibulum of the hair follicle and in the basal layer of interfollicular epidermis (Raick 1973 Klein-Szanto et al., 1980). The abundance of these cells during embryonic development, and their induction following carcinogenic doses of DMBA, suggested that they are both stem cells and target cells for tumor-initiating agents (Slaga and Klein-Szanto, 1983). The proportion of these cells increases up to 11-fold following treatment of...

Human Embryonic Stem Cells

In recent years, many species, including humans, have been included in stem cell research. Stem cell lines have been derived from human blastocysts (Thomson et al., 1998) and PGCs (Shamblott et al., 1998) with techniques very similar to those developed for mouse embryos. These lines have been designated with the same terminology of ES and EG cells, respectively. Like their mouse counterparts, these stem cells maintain a stable karyotype and perhaps can proliferate indefinitely in vitro. They...

Conclusion

The nephroblastoma, or Wilms' tumor, provides a compelling paradigm of a tumor originating in a defined pluripotent stem cell population. This has been aptly demonstrated histo-logically and confirmed biochemically. The expression patterns of most blastemal markers resemble the profiles observed for stem cells of putative preneoplastic lesions (i.e., the nephrogenic rests) and of the Wilms' tumors themselves. Most striking, however, is the genetic evidence that despite morphological...

Or Exogenous Reporter Genes

Transplantation of donor cells that can be distinguished from host liver cells by endogenous markers or exogeneous reporter genes is another widely used method for generating chimeric livers suitable for lineage analysis and cell fate determinations. However, interpretation of events in chimeric livers generated by transplantation can be difficult as there are several confounding variables that can greatly influence the results. One issue is the stability of marker gene expression. If the...

Differentiation Of Mouse Es Cells In Culture

Mouse ES cell differentiation can be achieved in vitro via several techniques. The withdrawal of gp130 agonists from ES cells in adherent culture results in loss of pluripotence, as indicated by downregulation of Oct4 expression, and formation of heterogeneous populations of cells morphologically distinct from ES cells (Smith, 1991). Although these cell populations have not been extensively characterized, they appear to comprise a limited number of cell types, predominantly a fibroblastic-like...

Existence Of Stem Cells In The Germline Two Types One Purpose

GSCs exist in many organisms, ranging from hydrazoan polyps, nematodes, arthropods, amphibians, birds, fishes, to reptiles and mammals (reviewed in Lin, 1997). Exceptions to this rule are some vertebrates, including mammals, that do not contain stem cells in the female germline (reviewed in Lin, 1997). GSCs can be classified into two types, stereotypic vs populational, according to how they self-renew. The main features of these two types of stem cells are discussed below. 5.2.1. STEREOTYPIC...

Heart Development In Drosophila

Basic mechanisms of heart development (cardiogenesis) are conserved between vertebrates and invertebrates. Remarkably, although the Drosophila heart is linear and thus totally different in the morphology of the looped and chambered heart of vertebrates, outstanding similarities exist concerning the embryonic origins and genes involved in the cardiac specification (Harvey, 1996 Olson and Srivastava, 1996 Bodmer and Venkatesh, 1998 Su et al., 1999). In this context, the homeobox gene tinman in...

Fiona C Mansergh phd Michael A Wride phd

Contrary to long held theory it has been shown recently that there are self-renewing stem cells in the adult central nervous system and that neuronal precursor cells can be derived in vitro from embryonic stem (ES) cells as well as other types of adult stem cells. Differentiation can be controlled by growth factors and culture conditions, such as, epidermal growth factor for the astrocyte lineage, and basic fibroblast growth factor for neuronal phenotypes, presumably by selection of stem cells...

Epithelial Cell Lineages In The Gi Tract

The GI tract comprises the oral cavity, pharynx, esophagus, stomach, small intestine, and colon. Each organ is histologically distinct, although throughout the tract an epithelial luminal lining with underlying vascular lamina propria forms the GI mucosa. The gastric glands open onto the stomach mucosal surface and are further subdivided into foveolar, isthmus, neck, and base regions. In the fundus, gastric glands contain surface mucous cells and mucous neck cells acid-secreting parietal...

Mechanism Of Stem Cell Formation

Degradation of Extracellular Matrix On amputation, the extracellular matrix (ECM) of bone, cartilage, muscle, nerve sheath, and dermal tissue is degraded, liberating osteocytes, chondrocytes, myofibers, Schwann cells, and fibroblasts from their tissue organization. The liberated cells then undergo dedifferentiation to become mesenchyme-like stem cells. Degradation of the ECM is accomplished by proteases. These include acid hydrolases such as cathepsin D and acid phosphatase (Ju and...

Stem Cells Of Gi Epithelium

Even though specific biomarkers for stem cells of normal gut epithelium are not yet available, these cells can be defined by two major criteria. First, morphologically, they are undifferentiated and exhibit embryonic cell-like features (Fig. 1) high nucleus-to-cytoplasm ratio, a nucleus with much diffuse chromatin and large reticulated nucleoli, and cytoplasm containing a few small organelles but many free ribosomes (Leblond, 1981 Karam, 1995). Second, functionally, they have a high capacity to...

Cell Lineages Scattered Along Gi Tract

ENTEROENDOCRINE CELL LINEAGES The pep-tide- or polypeptide-producing enteroendocrine cell lineages are scattered throughout the GI epithelium. In mice, they represent about 7 of all cells in the stomach body (Karam and Leblond, 1992) and 3 in the pyloric antrum (Lee, 1985). In the small intestine, they are more abundant in the crypts than in the villi and generally form about 0.5 of all crypt-villus cells (Cheng and Leblond, 1974b). They form about 0.4 of cells in the colon (Tsubouchi...

Gene Therapy

The use of stem cells is a potential method of delivering genes of interest into the heart for therapeutic purposes. In the rat, heart-specific expression of the P-galactosidase gene has been shown demonstrating the feasibility of this approach for clinical therapies (Griscelli et al., 1998). 23.4.1. HEART One potential application for gene therapy is preventing ischemic myocardial damage by protecting tissue from repeated ischemia reperfusion injury. To this end, Melo et al. (2002) delivered...

C

More, D-LIF was shown to act as a proliferative stimulus on fully differentiated cardiomyocytes and increased their longevity (Bader et al., 2000). LIF receptor mRNA has been detected in yolk sac visceral endoderm (Passavant et al., 2000), which is thought to be involved in cardiogenesis. In EBs differentiation of primitive extraembryonic endoderm to visceral and parietal endoderm has been studied in detail (Boller et al., 1987 Sauer et al., 1998 Bader et al., 2001) and has been demonstrated to...

Introduction

In vivo analysis of hepatic stem progenitor cells is required for defining the fate of specific cell populations. Moreover, if stem cells are to be utilized for cell therapy, it is essential to demonstrate mechanisms concerning cell engraftment, proliferation, and function, similar to studies with primary hepatocytes (Gupta et al., 1999b). The correction of diseases in specific animal models following stem cell transplantation will constitute an important step in developing cell therapy...

Future Prospects

Development to term of an offspring derived from a cloned embryo is a remarkable demonstration of plasticity, especially of even fully differentiated cells. This ability to become repro-grammed is dependent on placing the differentiated nucleus in the correct environment, i.e., oocyte cytoplasm. Investigations into the early events of nuclear reprogramming, and the oocyte factors involved, will enhance our understanding of cellular differentiation. Increasing our knowledge in this area will not...

Tb

Cellular composition of pulmonary acinus in early embryonic lung. (A) Mouse embryo on d 15 after conception (scanning electron microscopy). The pulmonary acinus consists of a short first-order (1) and two second-order (2) acinar tubules One of which has been cut off, arrow) with a saccular ending (S). The cuboid epithelium of the acinar tubule is sharply demarcated from the columnar epithelium of the connecting bronchiole. The most proximal type II cell is indicated (asterisk) (x1400)....

Possible Clinical Scenarios For Use Of Imaging In Different Stem Cell Therapy Approaches

A simplistic scenario for stem cell therapy for an organ regeneration after injury or infarct would involve the following 1. Generation of tracer cells by stably transducing the stem cells with a reporter gene. 2. Administration of unmodified stem cells mixed with the tracer cells to a patient either systemically or by a locoregional injection (e.g., intracerebral). 3. Monitoring of the localization, migration, homing, and persistence of stem cells by imaging tracer cells using reporter...

Systems For Mouse Es Cell Differentiation Exploiting Pluripotence In Culture For The Study Of Embryogenesis

FORMATION OF THE EARLY EXTRAEMBRYONIC LINEAGES The first differentiation event in EBs is formation of extraembryonic endoderm lineages from outer pluripotent cells. Disruption of FGF signaling, achieved by expression of a dominant-negative FGF receptor in ES cells, results in failure to form extraembryonic endoderm during EB differentiation (Chen et al., 2000), implicating FGF-mediated signaling in establishment of this lineage. Although the source and molecular identity of the FGF...

To Functional Tissue Architecture

What Are the Signals and How Are They Processed Sui Huang, md, phd and Donald E. Ingber, md, phd Specific regulatory inputs from the cell's environment influence cell and tissue differentiation soluble growth factors and insoluble extracellular matrix interactions, as well as less-specific signals, such as mechanical forces, can switch cells among different phenotypic fates. This behavior may be explained by the existence of different attractor states, which represent stable phenotypes,...

Cell Lineages In Body Of Stomach

In the body region of the stomach, the oxyntic epithelium in-vaginates to form short pits continuous with long tubular glands (Helander, 1981 Ito, 1987 Karam and Leblond, 1992). Each gland can be divided into isthmus, neck, and base regions (Fig. 2). In the mouse, the pit-gland unit is lined by a monolayer of about 200 cells (Karam and Leblond, 1992). All cells lining the pit-gland unit of the oxyntic epithelium originate from the stem cells. These cells are stationary, anchored in the isthmus...

Wilms Tumora Pediatric Problem

Wilms' tumor is predominantly a pediatric neoplasm, arising in some 1 in 10,000 children by age 15, although tumors may occur during fetal development or even well into adulthood (Bennington and Beckwith, 1975 Breslow et al., 1988). The vast majority of tumors (more than 75 ), however, are actually diagnosed by age 5. The relatively high frequency (i.e., 6 of all childhood neoplasms) makes it one of the most common solid pediatric cancers. Unlike the majority of adult tumors, though, the number...

Challenges For Future Research

IMPROVING MARKERS AVAILABLE FOR MEASURING THE DIFFERENTIATION STATE OF HEPATIC CELLS As can be seen from Table 1, there is a real problem of markers permitting the classification of cells, particulary among hepatoblasts, bile duct-cells, and oval cells. Judging from the careful analysis of Plescia et al. (2001), microarrays will come into increasing use for the definition of gene expression patterns of hepatic cell lines and their differentiated derivatives. Once the gene expression...

Models Of Stem Cell Biology

Stem cell-based models of development and proliferation have been proposed in a number of organs. These models have generally suggested the presence of a stem cell compartment with the potential to undergo many rounds of division. Divisions of stem cells are proposed to give rise to daughter cells that are stem cells or that join a population of transient-amplifying cells capable of undergoing clonal expansion, finally giving rise to a cell population that is fully differentiated but has...

Differentiation Studies

PLASTICTY Determination is a well-known concept in embryology (Hopper and Hart, 1985) that describes the progression of a totipotent oocyte into a collection of cells that is more restricted in the number of cell types into which they can differentiate. Cells become determined to differentiate along one of three germ layers and later become determined to differentiate into specific organs or cells within that layer. While it has generally been accepted that cells retained some...

Cell Line From Liver Diverticulum

A deliberate attempt to isolate a line of liver progenitor hepatoblast cells has been described by Rogler (1997). She dissected E9.5 mouse liver diverticuli and treated them as was formerly done to obtain embryonic stem cells dissociation and growth on fibroblast feeder layers. Colonies of polygonal cells, judged to be hepatoblasts, were selected for study. Only one retained this morphology and was able to grow at low density. Cells of this HBC-3 line presented a euploid karyotype. Several...

Stem Cells from Early Mammalian Embryos

Common Themes and Significant Differences and Anna-Katerina Hadjantonakis, phd A description of the potential of cells during embryonic development indicates that the first restriction of the totipoten-tiality in the zygote occurs during formation of the blastocyst when the outer layer of cells forms the trophectoderm, which will give rise to the placenta, and the inner cells form the inner cell mass (ICM), which will develop into the fetus and fetal membranes. At this point, the ICM cells lose...

Mixed morphologyPalmate

BMEL and MMH cell lines display different morphologies due to culture conditions. Monolayer cultures show the mixed morphology of BMEL cell lines containing palmate-like and epithelial cells, whereas MMH palmate cell lines are of homogeneous morphology. Cells cultured in bacteriological dishes form aggregates (5 d of culture). BMEL cells cultured in Matrigel form bile duct units, and MMH cells form branching bile duct tubules (10 d of culture). All magnifications are 100x except the...

Pierre Charbord md dr inserm

Bone marrow stromal cells make up the microenvironment for hematopoiesis. The prototype for stem cell and lineages is that of the hematopoietic stem cell (HSC), as demonstrated by clonal analysis. The fate of the HSC is determined largely by the microenvironment (niche) provided by the mesenchymal stem cells (MSC). MSCs give rise to cells constituting the hematopoietic microenvironnement i.e., stromal cells, endothelial cells, vascular smooth muscle cells (VSMCs), adipocytes, and osteoblasts...

A

Structural organization of clusters of developing cardiomyocytes in plated whole mount EBs. The EBs were immunostained with a monoclonal antibody directed against sarcomeric a-actinin. Shown are representative 6-d-old (A), 9-d-old (B), and 19-d-old (C) EBs. Note that no sarcomeric organization was visible in 6-d-old cardiac precursor cells. The bar in (A) represents 45 lm. The bars in (B) and (C) represent 15 m. (From Sauer et al., 2001a, with permission). developmental stages express...

B

Basal cell carcinoma, see Non-melanoma skin cancer Beckwith-Wiedemann syndrome, 279 BFU-E, burst forming unit embryo, 134 erythrocyte, 122 Blastema, 89-93 plasticity, 93 transdifferentiation, 93 Blastocyst, 2 Blastomere, 2 Blastula, 2 Bone marrow, angioblasts, 255 Bone marrow stem cells, and heart repair, 253,262 Bone marrow transplantation liver replacement 124,125 spleen colony formation, 124 stem cell plasticity, 124 Bone marrow transplantation in leukemias and lymphomas, 168-173 graft...

Bipotential Hepatic Cell Lines From Mice Of Multiple Genotypes

The cell lines described above originated from transgenic mice. However, the role of the transgene in cell line emergence was unknown. Recently, we were able to isolate similar cell lines from nontransgenic mouse embryos (Strick-Marchand and Weiss, 2002). The technique is simple, easily reproducible with mice of any genetic background, and thus widely applicable. Embryonic livers are dissociated and plated, and one waits until proliferating colonies of epithelial cells appear 6-12 wk later the...

Emma M A Ball phd and Gail P Risbridger phd

Development of the permanent mammalian kidney (metanephros) involves complex processes such as tissue induction, branching morphogenesis of epithelia, and mesenchyme-to-epithelium transition, which give rise to the two main components of the renal system the collecting ducts and the nephrons. While renal stem cell or embryonic progenitor cell populations have not been definitively identified, their existence is implied throughout development, during maintenance of the mature organ and in...

Molecular Control Of Human Liver Stem Cell Growth And Differentiation

Several families of cytokines and growth factors are potentially important in regulation of liver stem cell responses. In a series of comprehensive studies from Thorgeirsson's laboratory, a number of receptor ligand families were reported to be upregulated during activation or progression of rat oval cell growth and differentiation. These include FGFs, leukaemia inhibitory factor, SCF, transforming growth factor-a (reviewed in Grisham and Thorgeirsson, 1997). Important clues also come from...

Regis Doyonnas phd and Helen M Blau phd

The goal of the intense research on stem cells is for human application. Recently, knowledge of stem cells has progressed rapidly and experimental therapies are already in clinical trials. However, for more far reaching application and successful therapy much more remains to be learned about stem cells. There are many more questions than answers. What is a stem cell What different kinds are there Can they be obtained and manipulated What are the lineages that derive from stem cells, and how...

Pet Imaging Of Mutant Dhfrhsv1tk Fusion Gene Expression In Vivo

Dihydrofolate reductase (DHFR) (EC 1.5.1.3.) catalyzes the formation of tetrahydrofolate (THF) from dihydrofolate (DHF). The most significant consequence of DHFR inhibition by methotrexate (MTX) or trimethotrexate (TMTX) is a decrease in thymidylate biosynthesis by means of depletion of the N N10-methylene-THF pool resulting in DNA synthesis inhibition and cell death. MTX is used to treat acute lymphoblastic leukemia, lymphoma, gastrointestinal cancers, and breast cancer. However, antifolate...

Cell Lines Vs Primary Cultures

The use of cell lines for research carries several important caveats. One primary criticism concerning the use of cell lines is that the entire basis of generating or selecting for a cell line renders that cell line nonphysiological in that most of the cells are transformed and some are tumorigenic. Indeed, the base characteristic of a cell line is that it will expand in culture indefinitely. This alone makes these cells different from native cells. Additionally, the details of the origin and...

Mario A Bourdon phd and Richard EB Seftor phd

Microarray analysis of melanoma cell lines suggests that aggressive melanomas have a pluripotent, embryonic-like phenotype, implying the possibility of a stem cell origin for tumor components. Aggressive melanoma cells also form vascular structures and express endothelial-associated genes (including vascular endothelial-cadherin and EphA2) critical for vessel formation, indicating that the tumor cells have the plasticity to generate progeny, which express multiple cellular phenotypes with...

Genomics Gene Discovery And Stem Cells

Bioinformatic analysis of genes implicated in neural differentiation could be important in unraveling stem cell biology (Bain et al., 2000 Mansergh et al., 2000). The advantage of in vitro systems such as ES neural differentiation is that large amounts of material undergoing synchronous differentiation can be made available for analysis. Such systems have, to date, been invalu able in gene discovery projects intended to uncover novel regulators of differentiation. Subtractive libraries and...

D

Daughter cell, 3 Dedifferentiation, 3, 90, 496 Deep crypt secretory cells, 325 Dermal wound healing, 101-105 collagen formation, 103 events, 101-102 hematogenous cells, 103, 104 stem cells, 103 Determination, 4 Developmental origin of hematopoietic stem cells, 133 BL-CFC, 138 Flk-1, 137, 138 hemangioblast, 134, 135 intraembryonic sites, 134 liver, fetal, 135 long-term repopulation hematopoietic stem cell assay, 135 paraarotic splanchnopleure (P-Sp AGM), 134, 135 SCL, 138 T- and B-cell...

Nephroblastoma A Stem Cell Tumor

As described above, Wilms' tumors generally exhibit a tripha-sic histological phenotype with blastemal, stromal, and epithelial cell populations, although there is a continuum in the quantitative representation of each population. Thus, tumors may appear predominantly blastemal, epithelial, or stromal. While the blastemal and epithelial elements resemble the structures observed in the differentiating metanephros, the stroma can undergo heterologous differentiation to yield cartilage, adipose...

Role Of Embryonic Stem Cells In Development

LINEAGE SPECIFICATION AND PLURIPOTENT CELLS WITHIN THE EARLY EMBRYO The totipotent cells of the cleaving mammalian embryo compact to form a morula and become radially polarized. This ball of cells gives rise to the cystic Fig. 1. Overview of mouse embryonic development from fertilization to midgestation. After fertilization has taken place within the oviduct, the preimplantation stage embryo makes its way to the uterus. The first cell division, or cleavage, occurs approx 1 d after...

Culture

Dispersed mouse mammary epithelial cells have been shown to be able to recombine and grow to form a new gland within the epithelium-free mammary fat pad (Daniel, 1965 DeOme et al., 1978a, 1978b Medina et al., 1986). In these experiments, both normal and transformed mammary outgrowths were developed, indicating that both normal and abnormal mammary cells could exist within any given apparently normal glandular population. Alternative interpretations included the acquisition of an abnor mal...

Alastair J Strain phd Sarbjit S Nijjar phd and Heather A Crosby phd

Although until recently the existence of the liver stem cell was questioned, now the race is on to obtain and characterize the human liver stem cell for clinical therapeutic use for gene replacement, liver repopulation, drug development, and bioartificial liver support systems. Experimental models have identified cells at different stages in the hepatocyte lineage, including mature hepatocytes, bipotential ductular cells (so-called oval cells), as well as blood-derived periductular cells, as...

Extrinsic Mechanisms The Stem Cell Niche

It has long been implicated that the self-renewing division of GSCs is regulated by extrinsic signaling (reviewed in Lin, 1997). In mammalian systems, extrinsic signaling is mediated by hormones, growth factors, cytokines, and short-range cell-cell signaling pathways such as those involving Steel c-kit. In C. elegans, a laser ablation experiment has elegantly demonstrated that somatic signaling is required for germline maintenance (Kimble and White, 1981). Somatic signaling also plays an...

In Vivo Hematopoietic Potential Of Es Derived Cells

The ability of ES cells to generate many different somatic cells in vitro argues for their usage as a source for cell transplantation, provided that they can function in vivo. Accumulating studies demonstrate that in vitro-generated hematopoietic progenitors can function in vivo, although the generation of HSCs from ES cells has not been firmly established. Muller and Dzierzak (1993) have utilized in vitro-differentiated ES cells as donor cells in cell transfer studies using newborn Wv Wv and...

Mechanisms Of Pancreas Regeneration Can Mature Cells Transdifferentiate

Regeneration of pancreatic tissue, and especially of islets, has been studied using several experimental rodent models. In general, it can be said that pancreas does not seem to possess as impressive a regenerative potential as, e.g., liver. Nevertheless, chemically or mechanically caused injury is followed by at least a partial regeneration in rodents. When massive acinar cell necrosis is induced by administration of agents such as ethionin or caerulein, acute pancreatitis is induced. Numerous...

Reepithelialization And Stem Cells

Closure of the epidermis following injury is essential to reestablishing a functional homeostatic barrier over the entire body surface. The injury response of the epidermis initially represents a migratory response by keratinocytes from islands of viable cells within the wound and from around the wound's circumference (Odland and Ross, 1968). This migration represents an intricate interplay between ECM molecules present in the provisional ECM and the keratinocytes with little contribution from...

R

Reepithelialization, wound healing, 102, 103 Regeneration, 221, 397, 496 Regulatory signals, 45 Renal development, see Kidney morphogenesis Renal stem cells, see Kidney stem cells Repopulating stem cell unit assay (RESCU), 158-160 adult retinal stem cells, 212-213 cellular diversification of retina, 209 factors affecting potential, 210 gene targeting of, 213 growth factors and, 210 lineages, 210, 213, 216 loss of function studies, 214-215 molecular studies of, 213 origin of, 211 potential, 210...

P

P-glycoprotein, 123 Pancreas, histology, 429 duct ligation, 431-432 ontogeny, 430 regeneration, 431 Pancreatic stem cells, 417-436 activation of, 419 autoimmune insulitis, 417 cell lineage, 434 cell lines, 433 embryonic, 433 future, 425 location, 431 markers, 417, 420, 431 ontogeny, 430 organogenesis, 420-421, 430 plasticity, 417-436 regeneration, 431-432 therapy for diabetes, 425 transcription factors, 418, 430 transplantation, 422-424 Paneth cells, 323 Paraarotic splanchnopleure (P-Sp AGM),...

Definition Of The Renal Stem Cell

Several criteria must be satisfied if a particular cell type is to be considered a true organ-specific stem cell (reviewed in Watt and Hogan, 2000 Al-Awqati and Oliver, 2002). In the case of the kidney, as in other organs, the putative stem cell must be able to generate a number of different cell types found in that organ, a characteristic known as multipotency, and the stem cell must be capable of self-renewal. It has been hypothesized that when a mammalian stem cell divides, its daughter...

Pit Cell Lineage

Pre-Pit Cells Pre-pit cells represent about 17 of all isthmal cells and are usually located near the pit border. Both the morphological features and dynamic behavior of these cells are quite similar to those of the pre-pit cells in the isthmus region of the oxyntic pit-gland units (Karam and Leblond, 1993a Lee, 1985). 29.5.1.2. Pit Cells Pit cells are located in the pit region and represent about 180 cells per pit-gland unit. The mode of migration and structural features of these...

Signaling Activity Or Differentiation

Significant efforts are being made to develop novel approaches for imaging progenitor cell differentiation after their administration in vivo. One approach is based on the coexpression of a bea con reporter gene from a strong constitutive promoter to visualize the localization of transduced stem cells and their progeny tissues another reporter gene (different from the beacon) could be linked to a promoter element that is selectively activated at a certain stage of progenitor cell...

Hepatocyte Cell Lines

Although strictly hepatocyte cell lines do not fall within the scope of this chapter, it is necessary to mention some of them briefly, for their study has led to techniques and approaches that would later be useful for the appreciation of bipotential cell lines. Indeed, many of the hepatocyte lines, especially the less well-differentiated ones and or those whose differentiation is conditional, may be bipotential without this having been realized when the work was performed. Since the focus was...

O

Interconversion of stem cell identity. The expression of Oct4 is pivotal for maintenance of ES cell identity. Loss of Oct4 and stimulation of the MAPK pathway by exposure to FGF4 can change the developmental potential and identity of stem cells from the primitive ectoderm to that of the trophectoderm. associated genetic pathways, and only by genetically manipulating the expression of key intrinsic regulators can a change in developmental potential be achieved and hidden pluripotency...

In Vitro Models Of Wilms Tumor

Efforts to develop a renewable source of nephroblastoma tissue for studies of the biochemical and molecular pathogenesis of Wilms' tumor have been limited and largely unsuccessful. These have included the serendipitous immortalization of cultured tumor cells, the use of tissues from heterotransplants of spontaneous or chemically induced tumors, primary cultures of dissociated Wilms' tumors, or dissociated tissues transduced with a transforming virus. Of these approaches, none has provided a...

In Vivo Differentiation Of Pancreatic Stem Cells To Islets Of Langerhans

Islets of Langerhans are compact clusters of endocrine hormone-producing cells that, for most vertebrate species, are embedded within the acinar tissue of the pancreas (Fig. 1A). These clusters have evolved a cellular organization that optimizes rapid and highly regulated responses to elevated blood glucose levels. During embryogenesis, the pancreas forms from a fusion of the dorsal and ventral primordia. These two primitive glands, which Edited by S. Sell Humana Press Inc., Totowa, NJ appear...

Carcinogenesis Protocols Producing Progenitor Cellderived

Recent studies indicate that progenitor cell activation is a constant feature of viral hepatocarcinogenesis. Patients with chronic HCV and HBV infections often exhibit extensive oval cell proliferation, usually in close proximity to regenerating nodules and HCC (Hsia et al., 1992 Lowes et al., 1999). Approximately 50 of the HCCs found in HBV-positive individuals express both oval cell and hepatocyte markers, a percentage similar to CDE diet-induced carcinomas in the rat. These observations...

Of Vascular Structures Augments Survival And Function Of Cardiomyocyte Precursors

An additional explanation for the poor survival of transplanted cardiomyocytes or skeletal myoblasts may be that viability and prolonged function of transplanted cells requires an augmented vascular supply. Whereas many transplanted cardiomyocytes die by apoptosis, cultured cardiomyocytes that incorporate more vascular structures in vivo demonstrate significantly greater survival (Ogawa et al., 1999). Moreover, in situations in which transplanted cardiomyocyte precursors contained an admixture...

Human Angioblasts Protect Hypertrophied Endogenous Cardiomyocytes Against Apoptosis

By concomitantly staining rat tissues for the myocyte-specific marker desmin and performing DNA end labeling using the TUNEL technique, temporal examinations demonstrated that the infarct zone neovascularization induced by injection of human angioblasts prevented an eccentrically extending proapoptotic process evident in saline controls. Thus, at 2 wk postinfarction, myocardial tissue of LAD-ligated rats that received saline demonstrated sixfold higher numbers of apopto-tic myocytes compared...

Conclusions And Implications For Stem Cells From Adults

It is apparent that ES and EG cells have abnormal imprinting profiles, or changes in allele-specific methylation and expression patterns. The changes appear to be more significant in EG cells, and this is probably due to their derivation from PGCs that have undergone a significant amount of imprinting erasure, or are poised to do so. Because some imprinted genes are involved in growth and control of the cell cycle (e.g., Igf2, Igf2r, and Cdckn1c, and their dysregulation is implicated in cancer...

Stem Cells Derived From Early Mouse Embryos

EC CELLS EC cells were first derived by culturing cells from spontaneous teratocarcinomas that occur in the testes or ovaries of certain strains of mice. These spontaneous tumors arise from the germ cells and are capable of differentiation into many cell types such that the tumors resemble embryonic development gone awry. A tumor might contain several types of epithelia, areas of bone and cartilage, muscle, fat, and hair, all mixed together in Fig. 3. Totipotent and pluripotent cells in...

Cardiomyogenesis Of Es Cells

Studies in the in vitro EB model have revealed a strictly regulated program of cardiomyogenesis that is triggered by specific signaling molecules and mediated by tissue-specific transcription factors. This program controls the specification of cardiomyocytes from mesodermal stem cells and the subsequent activation of genes involved in cardiac force generation. During EB differentiation toward functional cardiomyocytes, a number of transcription factors known to play a critical role in early...

Haifan Lin phd

Germline stem cells (GSCs) serve as the self-renewing source for the continuous production of gametes in diverse organisms. These stem cells can be classified into two types stereotypic and populational-according to how they self-renew. Stereotypic GSCs self-renew by asymmetric division, producing a daughter stem cell and a differentiated daughter cell. An example is the Drosophila ovary. Each ovariole contains two to three GSCs at its apical region. These cells divide to produce one daughter...

Rat Liver Epithelial Stemlike Cells Wbf344

The pioneering work of Coon (1968) established that epithelial cell colonies can be cloned from low-density cultures inoculated with collagenase-digested suspensions of rat liver. This work was then extended by J. W. Grisham and coworkers, who have contributed an exhaustive characterization of WB-F344 rat epithelial cells from adult liver. This section provides an overview of this work as a preamble to discussing other cell lines. In 1980, Grisham suggested that long-term propagable hepatic...

Potentiality Of Adult Epithelial Tissues

Glandular organs are generally composed of an epithelial parenchyma surrounded by stroma. For a long time the stroma was considered to be a supporting matrix that aided in organ function. For example, the fibromuscular prostatic stroma provides the force needed for ejaculation, while smooth muscle in the gut provides the peristaltic action needed to move food. It is now clear that the stroma plays an active role both in development, in which mesenchyme directs epithelial differentiation, and in...

Multipotential Cells In Early Mammalian Development

Throughout mammalian development, there exist only a few proven totipotent cells. Following fertilization, the zygote has the potential to differentiate into all the cell types of the fetal membranes and placenta, as well as all the cell types of the body, a capacity that defines totipotency. As the cleavage divisions take place, the earliest blastomeres also share this capacity to give rise to all cell types. However, by the time the blastocyst forms, cells have become limited and fixed in...

Conclusion And Research Questions

Amphibians create stem cells for limb, lens, and NR regeneration by a process of histolysis and dedifferentiation that involves the proteolytic degradation of ECM, loss of phenotypic structure, and renewed cell cycling. Dedifferetiation involves changes in the shape of cells liberated from their tissue matrix loss of cell-surface proteins and proteoglycans, and, in the case of myofibers, the dismantling of a highly differentiated contractile system. The FGF family of growth factors and...

Pet Imaging Of Reporter Gene Expression Driven By Endogenous Moleculargenetic Processes

Imaging regulation of endogenous gene expression in living animals (and potentially in human subjects) using noninvasive imaging techniques will provide a better understanding of normal and cancer-related biological processes. Modern molecular techniques provide the opportunity to design specific reporter gene constructs, in which the reporter gene is placed under the control of different promoter enhancer elements. For example, they can be always turned on by constitutive promoters (such as...

Characterization Of Hscs

MATURATION PATHWAY OF MURINE PHSCs To characterize more fully the surface markers of murine PHSCs, our laboratory developed a five-color FACS sorting technique and analyzed murine PHSCs by testing different subsets of fractionated bone marrow cells with the competitive repopulation assay (Zhao et al., 2000). The very primitive PHSCs in adult murine bone marrow harbor the characteristic surface marker profile of L- l0, S+, K+, 38+, 34-. These cells appear to mature into L- l0, S+, K+,...

Intracellular Stem Cell Mechanism Symmetry Vs Asymmetry

The very nature of stem cells determines that they should possess a robust cell-cycle program that is tightly regulated by signal ing from the niche. For stereotypic stem cells, it is also important to have a precise asymmetry-generating mechanism. The asymmetric mechanism may consist of asymmetrically expressed and or segregated cell fate regulators and a cellular machinery responsible for their asymmetric segregation or for establishing an asymmetric exposure of the two daughter cells to...

Factors And Signals Promoting Cardiogenesis In Vertebrates

Identification of soluble growth factors, transcription factors, and signal cascades capable of priming cardiogenesis is a crucial issue for understanding heart development. In recent years, through applying the embryonic stem (ES) cell and knockout animal model, several soluble factors and intracellular transcription factors as well as intracellular signal transduction pathways have been recognized to be involved in heart formation. In mammalians, the heart is the first mesoderm-derived...

Proliferation Of Blastema Stem Cells

Wound Epidermis and Nerves are Required for Proliferation Continuous- and pulse-labeling studies with 3H-thymidine indicate that > 90 of blastemic cells will ultimately cycle during the regeneration of either larval or adult regenerating limbs. The actively cycling fraction of cells at any given time is lower in adult limbs, however, thus partly accounting for the fact that regeneration of adult limbs takes longer (Goldhamer and Tassava, 1987 Tomlinson and Barger, 1987)....

Animal Models For Nephroblastoma

Nephroblastoma occurs spontaneously in a variety of animals. In surveys of slaughterhouses, it is the most common tumor observed in swine, and both unilateral (80 ) and bilateral disease (20 ) have been noted (Migaki et al., 1971). Classic nephroblastomas arise frequently in chickens (Feldman and Olson, 1965), and tumors are readily induced with a myeloblastosis virus (Walter et al., 1962). While tumors have been reported in cattle, the incidence is relatively low (1 of 302 renal tumors)...

Therapeutic Vasculogenesis By Epc Transplantation

Recently, the regenerative potential of stem cells has been under intense investigation. In vitro, stem and progenitor cells possess the capability of self-renewal and differentiation into organ-specific cell types. In vivo, transplantation of these cells may reconstitute organ systems, as shown in animal models of diseases (Anklesaria et al., 1987 Lindvall et al., 1990 Asahara et al., 1997 Flax et al., 1998 Evans et al., 1999 Kalka et al., 2000b). By contrast, differentiated cells do not...

Petct Ci

Paradigm for imaging HSV1-tk reporter gene expression with FIAU reporter probe. The HSV1-tk gene complex is transfected into stem cells by a vector in vitro or is coexpressed along with another therapeutic gene after in vivo administration of a gene delivery vector (left). Inside the transfected cell, the HSV1-tk gene is transcribed to HSV1-tk mRNA and then translated on the ribosomes to a protein (enzyme), HSV1-TK. After administration of a radiolabeled FIAU and its transport into the...

Cellular Composition And Origin Of The Lung Epithelium

CELL TYPES AT DIFFERENT AIRWAY LEVELS The respiratory tract in the mammalian lung (Fig. 1) is subdivided into the air-conducting bronchial system (components trachea, bronchi, and bronchioles) and the gas-exchanging respiratory system with its units, the pulmonary acini (components respiratory bronchioles, alveolar ducts, and alveolar sacs). Light and electron microscopy have identified notable differences in cell composition in different airway generations between humans and common...

Gilbert H Smith phd

A major interest in mammary stem cells relates to their potential role in the development of mammary cancer. The role of stem cells in development of premalignant and malignant lesions is exemplified by the study of the lesions, that develop in the mammary glands of mice infected with mouse mammary tumor virus. In addition, fragments or dispersed cells from the mammary glands of old or young mice possess equivalent ability to repopulate a cleared mammary fat pad through serial passages before...

Are Adult Stem Cells Located In Pancreatic Ducts

Where could the pancreatic stem cells be located in the adult organ Most investigators have been looking for islet progenitor cells (IPCs) in the pancreatic ducts, based on several arguments 1. The ducts are reminiscent of the early embryonic stage wherein pancreatic endodermal cells are organized in ducts or ductlike structures, at a time when there are not yet islets or acini. 2. Both in the fetal pancreas and in islet regeneration models, islet cells are seen to bud from the ductal lining...

Contributors

French Anderson, md, Gene Therapy Laboratories, USC Keck School of Medicine, Norris Cancer Center, Los Angeles, CA Takayuki Asahara, md, phd, Cardiovascular Research and Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Medford, MA Kurtis I. Auguste, md, Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA Stephen M. Baird, md, Professor of Pathology, University of California San Diego, and Chief Laboratory Services, VA...

Identification Of Hscs

Identification and isolation of PHSCs is a first step in order to study function. Because of the limited frequency of the PHSC in the bone marrow, major efforts have been made to obtain pure stem cells for both clinical and research purposes. Clinically, transplantation of pure stem cells should eliminate graft-vs-host disease as well as the reintroduction of malignancies from a research viewpoint, pure stem cells would facilitate the study of stem cell regulation in vivo and in vitro, which...

Alan O Perantoni phd

The histological appearance of nephroblastoma, or Wilms' tumor, closely resembles the histodifferentiation of the kidney from primitive metanephrogenic tissue. This is classically one of the tumors for which pathologists first recognized the possible role of stem cells in cancer as the blastemal cells from the nephroblastoma behave as pluripotent stem cells differentiating along multiple defined pathways. Wilms' tumors may appear predominantly blastemal, epithelial, or stromal are associated...

Wendy C Weinberg phd and Stuart H Yuspa md

Mosaic pattern analysis and genetic mutations common to all cells of a cancer show that squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), as well as squamous dysplasias, are clonal, whereas focal hyperplasias are polyclonal. One compartment of putative stem cells in the skin is located in the bulge of the hair follicle. Cells in this compartment are multipotent and can give rise to progeny that differentiate into any of the epidermal cells or adnexal organs. The interfollicular...

Cell Lineages In Colon

The epithelial lining of the colon invaginates to form numerous crypts (Fig. 5). It is estimated that the mouse colon includes about 700,000 crypts (Cheng and Bjerknes, 1985). The size of crypts and their lining cell types vary in the ascending and descending portions of the colon. In the ascending colon, crypts are shorter (about 20 vs 30 cell positions) and are populated by a smaller number of cells (about 300 vs 700 cells crypt) than in the descending colon. Cell types in the descending...

Evidence For Renal Stem Cells

In epithelia during collecting duct formation, the existence of renal stem cells is assumed, but the number of distinct populations in the kidney is still a contentious issue. Historically, it was believed that the two major epithelial compartments in the kidney are derived from different cell populations that is, the ureteric bud epithelium gives rise to the collecting duct system while the metanephric mesenchyme gives rise to the nephrons. According to this hypothesis, cells isolated from the...

Ian Wilmut and Lesley Ann Paterson phd

Development to term of a cloned offspring derived from an embryo created by somatic cell nuclear transfer is a remarkable demonstration of adult cellular plasticity. Reconstruction of embryos by transfer of human cells into enucleated oocytes (therapeutic cloning) is one potential source of pluripotent embryonic stem (ES) cells for cell replacement therapy. Furthermore, ES cell lines that are derived by this method should be histocompatible with the patient who supplied the donor cells. In...

Selective Activation Of Rodent Liver Progenitor Cells

In most animal models, activation of progenitor cells requires treatment with agents that severely compromise the proliferative capacity of hepatocytes but have little or no effect on progenitor cells, presumably because progenitors lack the cytochrome p450s needed to generate mitoinhibitory metabolites. 2-Acetylamino-fluorene (2-AAF), a liver carcinogen that is effective in blocking the regenerative capacity of hepatocytes at noncarcinogenic doses, has been used for this purpose in several...

Into The Future

We have touched on the many possibilities for NSCs as therapeutic tools for the future. Will these multipotent cells truly be a godsend or just a devil in a trypan blue dress Time and further research will be the judge, but the evidence is mounting that clearly points to their place among the armamentarium of therapeutic weapons. Nevertheless, many aspects concerning the clinical potential of NSCs remain speculative and much work needs to be done (Snyder and Park, 2002). There are many...

Field Cancerization Hypothesis And Patch Size

In a study of 783 resected head and neck carcinomas by Slaughter et al. (1953), multiple, synchronous premalignant primary foci were present in areas outside and overlapping the original invasive squamous carcinoma. This led to the field cancerization hypothesis that an initial carcinogenic stimulus induces neoplastic transformation in multiple cells within a tissue. Premalignant regions of epithelium adjacent to the initial primary tumor are termed field cancerizations and are believed to...

Pet Imaging Of Adoptive Tcell Transfer

The recent work at MSKCC on imaging trafficking and targeting of genetically HSV1-tk-labeled T-cells after in vitro loading with 131I FIAU for gamma camera imaging (early trafficking and targeting) (Koehne et al., 2002) and repetitive administration of 124I FIAU in vivo for PET imaging (late trafficking and targeting) (Doubrovina et al., 2002) demonstrated the feasibility of implementing this combined approach, which could be easily applied to imaging stem cells in vivo. Fig. 12. BLI of...

Differentiation And Proliferation Disorders In Early Phases Of Prostatic Cancerogenesis

HGPIN is the most likely precursor of prostate cancer (Bostwick, 1996 Montironi et al., 1996). This lesion usually arises in preexisting ducts and duct-acinar units of the peripheral zone and shares cytological features with intermediate and high-grade carcinoma but retains basal cell differentiation (Bostwick, 1996). Autopsy studies indicate that PIN precedes carcinoma by 10 yr and more. HGPIN is currently the most significant risk factor for prostate cancer. Its identification in prostatic...

Strategies Using Cell Therapy to Induce Cardiomyocyte Regeneration in Adults with Heart Disease

Congestive heart failure remains a major public health problem and is frequently the end result of cardiomyocyte apoptosis and fibrous replacement after myocardial infarction (MI), a process referred to as left ventricular remodeling. Cardiomyocytes undergo terminal differentiation soon after birth and are generally considered to withdraw irreversibly from the cell cycle. In response to ischemic insult, adult cardiomyocytes undergo cellular hypertrophy, nuclear ploidy, and a high degree of...