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...

References

M., et al. (1997) Independent requirement for ISL1 in the formation of the pancreatic mesenchyme and islet cells. Nature 385 257-260. Al-Abdullah, I. H., Ayala, T., Panigrahi, D., et al. (2000) Neogenesis of pancreatic endocrine cells in copper-derived rat models. Pancreas 21 63-68. Bhutani, M. S. (1999) Interventional Endoscopic Ultrasound, Harwood, Amsterdam, The Netherlands. Bjorson, C. R. R., Reitza, R. L., Reynolds, B. A., et al. (1999) Turning brain into...

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...

Histology Of Pancreas

The mammalian pancreas is composed of six epithelial cell types that can be discriminated on the basis of phenotypic and functional characteristics the two types of exocrine cells, acinar and ductal cells, and four types of endocrine cells, a, P, 8, and PP-cells. These cell types can be recognized by their major secretory products, which are the digestive proenzymes in the case of acinar cells (e.g., amylase, trypsin, chymotrypsin, lipase, ribo-nuclease), and the hormones glucagon, insulin,...

Kathyjo A Jackson phd and Margaret A Goodell phd

Cellular-based therapies may be a future strategy for treatment of cardiac injury. Full differentiation of the heart leaves an organ without a stem cell population to respond to injury. This can be addressed by providing cardiomyocyte precursors from embryonic or adult stem cells. The coronary vasculature derives from both vasculogenesis from the putative hemangioblast and angiogenesis by sprouting from newly formed vessels from the proepicardium, which is formed from villi-like protrusions of...

Mouse Hsc Assays

The term hematopoietic stem cell has been a much abused and misunderstood term that has been used in its loosest form to describe any hematopoietic progenitor cell. A major reason for the frequent incorrect use of the term in the literature is that generally stem cells have been operationally defined based on the assay used to detect and enumerate them. Over time stem cell assays have changed considerably, especially those for the most commonly used hematopoietic model, the mouse. We now know...

Cellular Biology Of Prostatic Epithelium

The prostatic epithelium has a complex composition of three cell types differing in their hormonal regulation and marker expression (Fig. 2). The most prevalent phenotype consists of secretory luminal cells expressing prostate-specific antigen (PSA) and cytokeratins (CKs) 8 and 18 (Nagle et al., 1991 Xue et al., 1998). Basal cells, the second most important phenotype, maintain normal epithelial-stromal relation and express high-molecular-weight cytokeratins (Wernert et al., 1987 Bonkhoff,...

Nschost Interactions A Twoway Street

There is growing evidence to support the notion that donor NSCs and host tissue communicate in a reciprocal fashion. While it has been known that a given host CNS environment is instructive of donor stem cells, influencing their migration and differentiation patterns, the donor NSCs are apparently equally capable of manipulating their milieu. While it seems evident that NSCs that have been engineered to express foreign gene products may influence the host CNS into which they have been...

Tumors In Gi Tractmonoclonal Or Polyclonal In Origin

The GI tract undergoes constant self-renewal throughout the lifetime of its host, with cell proliferation maintaining normal homeostasis by responding to the increases and decreases in cell death determined by the health of the tissue. The huge numbers of daily mitotic events in this complex homeostatic regulation make the GI tract one of the most common sites of human cancers (Cutler et al., 1974). The life-span of a GI epithelial cell is shorter than the time taken to genetically induce...

Determination

Division of the fertilized egg results in the formation of a ball-like structure with a cavity on one end (the blastula). Until this stage, the cells divide by symmetric division, and all cells produced are totipotent. Invagination of one pole of the blastula leads to formation of the gastrula and establishment of the primitive germinal cell layers. During gastrulation and later formation of the fetus, the daughter cells lose potential as they gain...

Ian Ponting phd Yi Zhao md and w French Anderson md

The small population of pluripotent hematopoietic stem cells PHSCs in the bone marrow consists of short-term reconstituting cells STRCs and long-term reconstituting cells LTRCs , based on how quickly the transplanted cells can produce progeny in an irradiated recipient. They can be purified using a combination of cell size density fluorescent dye uptake resistance to cytotoxic chemicals and cell-surface markers including Thy 1.1 T , Sca-1 S , c-kit K , lineage L , CD38 38 , and CD34 34 . Using...

David L Stocum phd

Salamanders, newts, and frogs can regenerate limbs, spinal cord, neural retinal and lens of the eye, cardiac muscle, and so on from adult stem cells that dedifferentiate from differentiated cells at the site of injury and then differentiate in response to signals derived from serum and adjacent tissues. Regeneration of the limb requires degradation of the extracelluar matrix, which liberates osteocytes, chondrocytes, myofibers, Schwann cells, and fibroblasts to undergo dedifferentiation to form...

Stem Cell Origin of Cell Lineages Proliferative Units and Cancer in the Gastrointestinal Tract

Mairi Brittan, bsc and Nicholas A Wright, md, phd The gastrointestinal GI stem cell has the ability to differentiate into every epithelial lineage in the GI tract and is proposed as the target of GI carcinogenesis. There is considerable difference in the epithelial tissue of the GI tract including the oral cavity, pharynx, esophagus, stomach, small intestine, and colon, yet each appears to have a common stem cell that can give rise to both metaplasia and cancer throughout the GI tract. These...

Selective Regulation And Robustness Of Cell Behavioral States

MUTUAL EXCLUSION OF PROLIFERATION AND DIFFERENTIATION The often used metaphor of switch to describe how cells change among different stable behavioral states or fates reflects the implicit perception of cell fates as distinct, mutually exclusive states, separated by all-or-none transitions. One important cell fate switch is the transition from a growth state to a differentiated state cells undergoing terminal differentiation commonly lose the capacity to proliferate Goss, 1967 . This...