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Juan Carlos Polanco,
Mirabelle S H Ho,
Bei Wang,
Qi Zhou,
Ernst Wolvetang,
Elizabeth Mason,
Christine A Wells,
Gabriel Kolle,
Sean M Grimmond, Ivan Bertoncello,
Carmel O'Brien,
Andrew L Laslett
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ABSTRACT: Human induced pluripotent stem cells (hiPSC) have the potential to generate healthy cells and tissues for the study and medical treatment of a large number of diseases. The utility of putative hiPSC-based therapies is constrained by a lack of robust quality-control assays that address the stability of the cells or their capacity to form teratomas after differentiation. Here we report that virally derived hiPSC, but not human embryonic stem cells (hESC) or hiPSC derived using episomal non-integrating vectors, exhibit a propensity to revert to a pluripotent phenotype following differentiation. This instability was revealed using our published method to identify pluripotent cells undergoing very early-stage differentiation in standard hESC cultures, by fluorescence activated cell sorting (FACS) based on expression of the cell surface markers TG30 (CD9) and GCTM-2. Differentiated cells cultured post-FACS fractionation from virally-derived hiPSC lines re-acquired immunoreactivity to TG30 (CD9) and GCTM-2, formed stem cell-like colonies and re-expressed canonical pluripotency markers. Furthermore, differentiated cells from pluripotency-reverting hiPSC lines generated teratomas in immunocompromised mice, raising concerns about their safety in downstream applications. In contrast, differentiated cell populations from hESC and episomally derived hiPSC did not show any of these abnormalities. Our assays may be used to identify "unsafe" hiPSC cell lines and this information should be considered when selecting hiPSC lines for clinical use and indicate that experiments using these "unsafe" hiPSC lines should be interpreted carefully.
Stem Cells 06/2013; · 7.78 Impact Factor
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ABSTRACT: Recognition of the potential of stem cell based therapies for alleviating intractable lung diseases has provided the impetus for research aimed at identifying regenerative cells in the adult lung, understanding how they are organised and regulated, and how they could be harnessed in lung regenerative medicine. In this review we describe the attributes of adult stem and progenitor cells in adult organs, and how they are regulated by the permissive or restrictive microenvironment in which they reside. We describe the power and limitations of experimental models, cell separative strategies and functional assays used to model the organisation and regulation of adult airway and alveolar stem cells in the adult lung. The review summarises recent progress and obstacles in defining endogenous lung epithelial stem and progenitor cells in mouse models and in translational studies.
Respirology 02/2013; · 2.42 Impact Factor
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ABSTRACT: The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) directly regulates the development of Paneth cells (PC) and influences proliferation and cell fate in the small intestine (SI). In the present study, we have examined the role of CSF-1 and the CSF-1R in the large intestine, which lacks PC, in the steady state and in response to acute inflammation induced by dextran sulfate sodium (DSS). As previously shown in mouse, immunohistochemical (IHC) analysis of CSF-1R expression showed that the receptor is baso-laterally expressed on epithelial cells of human colonic crypts, indicating that this expression pattern is shared between species. Colons from null and mice were isolated and sectioned for IHC identification of enterocytes, enteroendocrine cells, goblet cells and proliferating cells. Both and mice were found to have colon defects in enterocytes and enteroendocrine cell fate, with excessive goblet cell staining and reduced cell proliferation. In addition, the gene expression profiles of the cell cycle genes, , , , and were suppressed in colonic crypt, compared with those of WT mice and the expression of the stem cell marker gene was markedly reduced. However, analysis of the proliferative responses of immortalized mouse colon epithelial cells (lines; Immorto-5 and YAMC) indicated that CSF-1R is not a major regulator of colonocyte proliferation and that its effects on proliferation are indirect. In an examination of the acute inflammatory response, male mice were protected from the adverse affects of DSS-induced colitis compared with WT mice, while female mice were significantly less protected. These data indicate that CSF-1R signaling plays an important role in colon homeostasis and stem cell gene expression but that the receptor exacerbates the response to inflammatory challenge in male mice.
PLoS ONE 01/2013; 8(2):e56951. · 4.09 Impact Factor
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ABSTRACT: Despite burgeoning interest in the potential of cellular therapies in lung regenerative medicine, progress in delivering these therapies has been confounded by a lack of knowledge about the identity of appropriate targets which can be harnessed to repair the lung, and the cellular and molecular factors which regulate their regenerative potential. While systematic analysis of lung development and cell lineage tracing studies in normal and perturbed animal models provides a framework for understanding the complex interplay of the multiple cell types, biomatrix elements and soluble and insoluble cytokines and factors that regulate lung structure and function, a reductionist approach is also required to analyze the organization of regenerative cells in the adult lung and identify the factors and molecular pathways which regulate their capacity to generate descendent lineages. In this review we describe recent progress in identifying and characterizing endogenous epithelial, mesenchymal and endothelial stem/progenitor cells in the adult lung using multiparameter cell separative strategies and functional in vitro clonogenic assays.
Stem Cells 02/2012; 30(5):811-6. · 7.78 Impact Factor
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ABSTRACT: A large body of evidence suggests hemopoietic stem cells (HSCs) exist in an endosteal niche close to bone, whereas others suggest that the HSC niche is intimately associated with vasculature. In this study, we show that transplanted hemopoietic stem and progenitor cells (HSPCs) home preferentially to the trabecular-rich metaphysis of the femurs in nonablated mice at all time points from 15 minutes to 15 hours after transplantation. Within this region, they exist in an endosteal niche in close association with blood vessels. The preferential homing of HSPCs to the metaphysis occurs rapidly after transplantation, suggesting that blood vessels within this region may express a unique repertoire of endothelial adhesive molecules. One candidate is hyaluronan (HA), which is highly expressed on the blood vessel endothelium in the metaphysis. Analysis of the early stages of homing and the spatial dis-tribution of transplanted HSPCs at the single-cell level in mice devoid of Has3-synthesized HA, provides evidence for a previously undescribed role for HA expressed on endothelial cells in directing the homing of HSPCs to the metaphysis.
Blood 06/2011; 118(6):1516-24. · 9.90 Impact Factor
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ABSTRACT: Air spaces of the mammalian lung are lined by a specialized epithelium that is maintained by endogenous progenitor cells. Within bronchioles, the abundance and distribution of progenitor cells that contribute to epithelial homeostasis change as a function of maintenance versus repair. It is unclear whether functionally distinct progenitor pools or a single progenitor cell type maintain the epithelium and how the behavior is regulated in normal or disease states. To address these questions, we applied fractionation methods for the enrichment of distal airway progenitors. We show that bronchiolar progenitor cells can be subdivided into two functionally distinct populations that differ in their susceptibility to injury and contribution to repair. The proliferative capacity of these progenitors is confirmed in a novel in vitro assay. We show that both populations give rise to colonies with a similar dependence on stromal cell interactions and regulation by TGF-β. These findings provide additional insights into mechanisms of epithelial remodeling in the setting of chronic lung disease and offer hope that pharmacologic interventions may be developed to mitigate tissue remodeling.
American Journal of Respiratory Cell and Molecular Biology 06/2011; 44(6):794-803. · 5.13 Impact Factor
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ABSTRACT: Adult mouse lung epithelial stem/progenitor cells (EpiSPC) can be defined in vitro as epithelial colony-forming units that are capable of self-renewal, and which when co-cultured with lung mesenchymal stromal cells (MSC) are able to give rise to differentiated progeny comprising mature lung epithelial cells. This unit describes a protocol for the prospective isolation and in vitro propagation and differentiation of adult mouse lung EpiSPC. The strategy used for selection of EpiSPC and MSC from adult mouse lung by enzymatic digestion and flow cytometry is based on the differential expression of CD45, CD31, Sca-1, EpCAM, and CD24. The culture conditions required for the differentiation (co-culture with MSC) and expansion (stromal-free culture with FGF-10 and HGF) of EpiSPC are described.
Current protocols in stem cell biology 01/2011; Chapter 2:Unit 2G.1.
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ABSTRACT: Advances in stem cell technologies in recent years have generated considerable interest in harnessing the potential of adult and embryonic stem cells in regenerative medicine. Stem cell-based therapies are a particularly attractive option for the treatment of intractable lung diseases for which current therapies are essentially palliative. Proof-of-principle experiments in animal models demonstrate the efficacy of exogenous stem cells in mediating lung repair by attenuating fibrotic responses to injury, but also suggest that their ability to contribute to lung epithelial regeneration and repair is limited. Consequently, attention has turned to endogenous lung stem cells as targets or vehicles for the delivery of lung regenerative therapies. In this article, we discuss the potential and promise of endogenous lung stem cells in regenerative medicine, and the problems and challenges faced by researchers and clinicians in harnessing their potential to repair the lung.
Expert Review of Respiratory Medicine 06/2010; 4(3):349-62.
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ABSTRACT: The role of lung epithelial stem cells in maintenance and repair of the adult lung is ill-defined, and their identity remains contentious because of the lack of definitive markers for their prospective isolation and the absence of clonogenic assays able to measure their stem/progenitor cell potential. In this study, we show that replication of epithelial-mesenchymal interactions in a previously undescribed matrigel-based clonogenic assay enables the identification of lung epithelial stem/progenitor cells by their colony-forming potential in vitro. We describe a population of EpCAM(hi) CD49f(pos) CD104(pos) CD24(low) epithelial cfus that generate colonies comprising airway, alveolar, or mixed lung epithelial cell lineages when cocultured with EpCAM(neg) Sca-1(pos) lung mesenchymal cells. We show that soluble fibroblast growth factor-10 and hepatocyte growth factor partially replace the requirement for mesenchymal support of epithelial colony formation, allowing clonal passaging and demonstration of their capacity for self-renewal. These data support a model in which the adult mouse lung contains a minor population of multipotent epithelial stem/progenitor cells with the capacity for self-renewal and whose descendants give rise to airway and alveolar epithelial cell lineages in vitro.
Proceedings of the National Academy of Sciences 01/2010; 107(4):1414-9. · 9.68 Impact Factor
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Huiling Xu,
Kuhendra Balakrishnan,
Jordane Malaterre,
Matthew Beasley,
Yuqian Yan,
Jeroen Essers,
Esther Appeldoorn,
Jonathan M Tomaszewski,
Jonathan M Thomaszewski,
Melisa Vazquez,
Sandra Verschoor,
Martin F Lavin, Ivan Bertoncello,
Ivan Bertonchello,
Robert G Ramsay,
Michael J McKay
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ABSTRACT: Approximately half of cancer-affected patients receive radiotherapy (RT). The doses delivered have been determined upon empirical experience based upon average radiation responses. Ideally higher curative radiation doses might be employed in patients with genuinely normal radiation responses and importantly radiation hypersensitive patients would be spared the consequences of excessive tissue damage if they were identified before treatment. Rad21 is an integral subunit of the cohesin complex, which regulates chromosome segregation and DNA damage responses in eukaryotes. We show here, by targeted inactivation of this key cohesin component in mice, that Rad21 is a DNA-damage response gene that markedly affects animal and cell survival. Biallelic deletion of Rad21 results in early embryonic death. Rad21 heterozygous mutant cells are defective in homologous recombination (HR)-mediated gene targeting and sister chromatid exchanges. Rad21+/- animals exhibited sensitivity considerably greater than control littermates when challenged with whole body irradiation (WBI). Importantly, Rad21+/- animals are significantly more sensitive to WBI than Atm heterozygous mutant mice. Since supralethal WBI of mammals most typically leads to death via damage to the gastrointestinal tract (GIT) or the haematopoietic system, we determined the functional status of these organs in the irradiated animals. We found evidence for GIT hypersensitivity of the Rad21 mutants and impaired bone marrow stem cell clonogenic regeneration. These data indicate that Rad21 gene dosage is critical for the ionising radiation (IR) response. Rad21 mutant mice thus represent a new mammalian model for understanding the molecular basis of irradiation effects on normal tissues and have important implications in the understanding of acute radiation toxicity in normal tissues.
PLoS ONE 01/2010; 5(8):e12112. · 4.09 Impact Factor
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Huiling Xu,
Kuhendra Balakrishnan,
Jordane Malaterre,
Matthew Beasley,
Yuqian Yan,
Jeroen Essers,
Esther Appeldoorn,
Jonathan M Tomaszewski,
Melisa Vazquez,
Sandra Verschoor,
Martin F Lavin, Ivan Bertoncello,
Robert G Ramsay,
Michael J McKay
PLoS ONE 01/2010; 5(9). · 4.09 Impact Factor
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ABSTRACT: The ultrastructural study of rare cells within their niche in situ is very difficult. We have developed a method for locating individual transplanted cells and simultaneously identifying and analyzing the molecules and cellular phenotypes surrounding them in situ using transmission electron microscopy. This innovative method involves triple immunogold labeling combined with serial ultrathin sectioning. We demonstrate the validity of this approach by examining the niche of individual transplanted cells from a population highly enriched for hemopoietic stem cells and the ultrastructural expression of two key stem cell regulatory molecules, hyaluronic acid and osteopontin. In addition, we describe the phenotypes of the surrounding cells.
Microscopy and Microanalysis 10/2009; 15(5):403-14. · 3.01 Impact Factor
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ABSTRACT: Paneth cells (PCs) secrete defensins and antimicrobial enzymes that contribute to innate immunity against pathogen infections within the mucosa of the small intestine. We examined the role of colony stimulating factor-1 (CSF-1) in PC development.
CSF-1-deficient and CSF-1 receptor (CSF-1R)-deficient mice and administration of neutralizing anti-CSF-1R antibody were used to study the requirement of CSF-1 for the development of epithelial cells of the small intestine. CSF-1 transgenic reporter mice and mice that express only the membrane-spanning, cell-surface CSF-1 isoform were used to investigate regulation by systemic versus local CSF-1.
Mice deficient in CSF-1 or CSF-1R had greatly reduced numbers of mature PCs. PCs express the CSF-1R, and administration of anti-CSF-1R antibody to neonatal mice significantly reduced the number of PCs. Analysis of transgenic CSF-1 reporter mice showed that CSF-1-expressing cells are in close proximity to PCs. CSF-1/CSF-1R-deficient mice also had reduced numbers of the proliferating epithelial cell progenitors and lamina propria macrophages. Expression of the membrane-spanning, cell-surface CSF-1 isoform in CSF-1-deficient mice completely rescued the deficiencies of PCs, proliferating progenitors, and lamina propria macrophages.
These results indicate local regulation by CSF-1 of PC development, either directly, in a juxtacrine/paracrine manner, or indirectly, by lamina propria macrophages. Therefore, CSF-1R hyperstimulation could be involved in hyperproliferative disorders of the small intestine, such as Crohn's disease and ulcerative colitis.
Gastroenterology 04/2009; 137(1):136-44, 144.e1-3. · 11.68 Impact Factor
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ABSTRACT: Originally identified as a marker specifying murine hematopoietic stem cells, the Sca-1 antigen has since been shown to be differentially expressed by candidate stem cells in tissues including vascular endothelium, skeletal muscle, mammary gland, and prostate of adult mice. In the adult murine lung, Sca-1 has previously been identified as a selectable marker for the isolation of candidate nonhematopoietic (CD45(-)), nonendothelial (CD31(-)) bronchioalveolar stem cells (BASC) located at the bronchioalveolar duct junction that coexpress surfactant protein C and the Clara cell specific protein. Our systematic analysis of CD45(-)CD31(-)Sca-1(+) cells in fetal, neonatal, and adult lung shows that very few of these cells are detectable prior to birth but expand exponentially postnatally coinciding with the transition from the saccular to the alveolar stage of lung development. Unlike candidate BASCs, the CD45(-)CD31(-)Sca-1(+)CD34(+) cell fraction we describe coexpresses immunophenotypic markers (Thy-1 and platelet-derived growth factor receptor alpha) that define lung fibroblastic rather than epithelial cells. The mesenchymal "signature" of the CD45(-)CD31(-)Sca-1(+)CD34(+) cell fraction is further confirmed by transcriptional profiling, by cell culture studies demonstrating enrichment for clonogenic lipofibroblastic and nonlipofibroblastic progenitors, and by immunohistochemical localization of Sca-1 in perivascular cells of the lung parenchyma. Although the CD45(-)CD31(-)Sca-1(+)CD34(+) cell phenotype does define endogenous clonogenic progenitor cells in the adult murine lung, our data indicate that these progenitors are predominantly representative of mesenchymal cell lineages, and highlights the pressing need for the identification of alternative markers and robust functional assays for the identification and characterization of epithelial and fibroblastic stem and progenitor cell populations in the adult lung.
Stem Cells 01/2009; 27(3):623-33. · 7.78 Impact Factor
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Benjamin B Williams,
Meg Wall,
Rebecca Yu Miao,
Brenda Williams, Ivan Bertoncello,
Michael H Kershaw,
Theo Mantamadiotis,
Michelle Haber,
Murray D Norris,
Anand Gautam,
Phillip K Darcy,
Robert G Ramsay
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ABSTRACT: Overexpression of the proto-oncogene c-Myb occurs in more than 80% of colorectal cancer (CRC) and is associated with aggressive disease and poor prognosis. To test c-Myb as a therapeutic target in CRC we devised a DNA fusion vaccine to generate an anti-CRC immune response. c-Myb, like many tumor antigens, is weakly immunogenic as it is a "self" antigen and subject to tolerance. To break tolerance, a DNA fusion vaccine was generated comprising wild-type c-Myb cDNA flanked by two potent Th epitopes derived from tetanus toxin. Vaccination was performed targeting a highly aggressive, weakly immunogenic, subcutaneous, syngeneic, colon adenocarcinoma cell line MC38 which highly expresses c-Myb. Prophylactic intravenous vaccination significantly suppressed tumor growth, through the induction of anti-tumor immunity for which the tetanus epitopes were essential. Vaccination generated anti-tumor immunity mediated by both CD4+ and CD8+ T cells and increased infiltration of immune effector cells at the tumor site. Importantly, no evidence of autoimmune pathology in endogenous c-Myb expressing tissues was detected as a consequence of breaking tolerance. In summary, these results establish c-Myb as a potential antigen for immune targeting in CRC and serve to provide proof of principle for the continuing development of DNA vaccines targeting c-Myb to bring this approach to the clinic.
Cancer Immunology and Immunotherapy 05/2008; 57(11):1635-45. · 3.70 Impact Factor
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ABSTRACT: Previous studies revealed that mAb BB9 reacts with a subset of CD34(+) human BM cells with hematopoietic stem cell (HSC) characteristics. Here we map BB9 expression throughout hematopoietic development and show that the earliest definitive HSCs that arise at the ventral wall of the aorta and surrounding endothelial cells are BB9(+). Thereafter, BB9 is expressed by primitive hematopoietic cells in fetal liver and in umbilical cord blood (UCB). BB9(+)CD34(+) UCB cells transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice contribute 10-fold higher numbers of multilineage blood cells than their CD34(+)BB9(-) counterparts and contain a significantly higher incidence of SCID-repopulating cells than the unfractionated CD34(+) population. Protein microsequencing of the 160-kDa band corresponding to the BB9 protein established its identity as that of somatic angiotensin-converting enzyme (ACE). Although the role of ACE on human HSCs remains to be determined, these studies designate ACE as a hitherto unrecognized marker of human HSCs throughout hematopoietic ontogeny and adulthood.
Blood 05/2008; 111(8):4055-63. · 9.90 Impact Factor
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ABSTRACT: The hematopoietic and vascular system of the developing embryo share a common mesodermal precursor, the hemangioblast (1–3). The primitive hematopoietic system arises in the extraembryonic blood islands of the yolk sac and the aorta-gonad-mesonephros
(AGM) region of the embryo. Multipotent hematopoietic stem cells from these primary sites then migrate through the developing
vascular system to colonize the fetal liver. Late in gestation, fetal liver-derived stem and progenitor cells seed the developing
bone marrow, spleen, and thymus. In the adult, the hematopoietic system comprises an hierarchically ordered, concatenated
series of stem and progenitor cell compartments of progressively restricted potentiality and proliferative capacity (4) (see
Fig. 1). These processes are precisely regulated by the complex interplay of cytokines, accessory cells, stromal cells, and matrix.
This involves the coordinated expression of many genes that directly or indirectly govern hematopoietic stem and progenitor
cell maintenance, maturation, lineage commitment, and differentiation; cell migration, mobilization, and sequestration; and
mature blood cell function (5–7).
Fig. 1.Schematic representation of the hierarchical organization of the hematopoietic system, surrogate stem, and progenitor cell
assays (34–36), and the level of expression of hematopoietic lineage antigens during lymphoid (33), myeloid, and erythroid cell maturation and differentiation. Abbreviations: LTRA-stem cells with long-term reconstituting
ability in vivo; CAFC-cobblestone area-forming cell; LTCIC- long-term culture-initiating cell; CFU-S12-colony-forming unit-spleen measured 12 d posttransplantation; HPP-CFC1 and −2-high-proliferative potential colony-forming cells stimulated by IL1α + IL3 + CSF-1 and IL3 + CSF-1 respectively; CFU-GEMM-colony-forming
unit-granulocyte/ erythrocyte/macrophage/megakaryocyte; CFU-GM-colony-forming unit-granulo-cyte/macrophage; BFU-E-burst-forming
unit-erythroid; LPP-CFC-low proliferative potential colony-forming cell.
02/2008: pages 181-203;
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ABSTRACT: Bone marrow (BM)-derived cells (BMCs) have demonstrated a myogenic tissue remodeling capacity. However, because the myoremodeling is limited to approximately 1%–3% of recipient muscle fibers in vivo, there is disagreement regarding the clinical relevance of BM for therapeutic application in myodegenerative conditions. This study sought to determine whether rare selectable cell surface markers (in particular, c-Kit) could be used to identify a BMC population with enhanced myoremodeling capacity. Dystrophic mdx muscle remodeling has been achieved using BMCs sorted by expression of stem cell antigen-1 (Sca-1). The inference that Sca-1 is also a selectable marker associated with myoremodeling capacity by muscle-derived cells prompted this study of relative myoremodeling contributions from BMCs (compared with muscle cells) on the basis of expression or absence of Sca-1. We show that myoremodeling activity does not differ in cells sorted solely on the basis of Sca-1 from either muscle or BM. In addition, further fractionation of BM to a more mesenchymal-like cell population with lineage markers and CD45 subsequently revealed a stronger selectability of myoremodeling capacity with c-Kit/Sca-1 (p < .005) than with Sca-1 alone. These results suggest that c-Kit may provide a useful selectable marker that facilitates selection of cells with an augmented myoremodeling capacity derived from BM and possibly from other nonmuscle tissues. In turn, this may provide a new methodology for rapid isolation of myoremodeling capacities from muscle and nonmuscle tissues.Disclosure of potential conflicts of interest is found at the end of this article.
Stem Cells 05/2007; 25(6):1364 - 1374. · 7.78 Impact Factor
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ABSTRACT: The procedures of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are routinely used in modern medicine to overcome infertility and, in animal husbandry, to propagate lines with compromised fertility. However, there remains concern that manual selection and injection of whole sperm into oocytes could contribute to pre- and postnatal developmental defects. To address this, we have used gene expression profiling and immunophenotyping to characterize offspring generated by these procedures. We used gametes from glutathione peroxidase 1 knockout (Gpx1-/-) mice as a sensitized screen responsive to oxidative stress from artificial reproduction technologies (ART). There were no differences between IVF and ICSI derived offspring in gene expression patterns, and minor differences in hematopoietic parameters. Furthermore there were only minor differences between these IVF and ICSI pups and those derived from natural mating. These data demonstrate for the first time in that there is no significant phenotypic affects of ICSI when compared to IVF and we identified a relatively minor influence of the artificial fertilization methods on phenotype of offspring compared with natural mating. These observations would support the use of ICSI for derivation of mutant mouse lines and may be of some importance for the use of this technique in human ART.
Molecular Reproduction and Development 05/2007; 74(4):512-9. · 2.53 Impact Factor
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ABSTRACT: It is now evident that hemopoietic stem cells (HSC) are located in close proximity to bone lining cells within the endosteum. Accordingly, it is unlikely that the traditional method for harvesting bone marrow (BM) from mice by simply flushing long bones would result in optimal recovery of HSC. With this in mind, we have developed improved methodologies based on sequential grinding and enzymatic digestion of murine bone tissue to harvest higher numbers of BM cells and HSC from the endosteal and central marrow regions. This methodology resulted in up to a sixfold greater recovery of primitive hemopoietic cells (lineage(-)Sca(+)Kit(+) [LSK] cells) and HSC as shown by transplant studies. HSC from different anatomical regions of the marrow exhibited important functional differences. Compared with their central marrow counterparts, HSC isolated from the endosteal region (a) had 1.8-fold greater proliferative potential, (b) exhibited almost twofold greater ability to home to the BM following tail vein injection and to lodge in the endosteal region, and (c) demonstrated significantly greater long-term hemopoietic reconstitution potential as shown using limiting dilution competitive transplant assays.
Stem Cells 05/2007; 25(4):1062-9. · 7.78 Impact Factor
