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1. Inhibition of SRC-mediated integrin signaling in bone marrow niche enhances hematopoietic stem cell function

Author

Irene Mariam Roy, P.V. Anu, Samantha Zaunz, Srinu Reddi, Aravind M. Giri, Rithika Saroj Sankar, Sarah Schouteden, Joerg Huelsken, Catherine M. Verfaillie, and Satish Khurana

Subjects
Biological sciences, cell biology, stem cells research, Science
Abstract

Summary: Interaction with microenvironmental factors is crucial for the regulation of hematopoietic stem cell (HSC) function. Stroma derived factor (SDF)-1α supports HSCs in the quiescent state and is central to the homing of transplanted HSCs. Here, we show that integrin signaling regulates Sdf-1α expression transcriptionally. Systemic deletion of Periostin, an Integrin-αv ligand, showed increased expression of Sdf-1α in bone marrow (BM) niche. Pharmacological inhibition or CRISPR-Cas9-mediated deletion of SRC, resulted in a similar increase in the chemokine expression in vitro. Importantly, systemic SRC-inhibition led to increase in SDF-1α levels in BM plasma. This resulted in a robust increase (14.05 ± 1.22% to 29.11 ± 0.69%) in the homing efficiency of transplanted HSCs. In addition, we observed enhancement in the recovery of blood cell counts following radiation injury, indicating an enhanced hematopoietic function. These results establish a role of SRC-mediated integrin signaling in the transcriptional regulation of Sdf-1α. This mechanism could be harnessed further to improve the hematopoietic function.

Published
2022
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2. Fetal hematopoietic stem cell homing is controlled by VEGF regulating the integrity and oxidative status of the stromal-vascular bone marrow niches

Author

Marion Mesnieres, Anna-Marei Böhm, Nicolas Peredo, Dana Trompet, Roger Valle-Tenney, Manmohan Bajaj, Nikky Corthout, Elena Nefyodova, Ruben Cardoen, Pieter Baatsen, Sebastian Munck, Andras Nagy, Jody J. Haigh, Satish Khurana, Catherine M. Verfaillie, and Christa Maes

Subjects
hematopoietic stem cell, niche, bone marrow, angiogenesis, stromal cell, hematopoiesis, Biology (General), QH301-705.5
Abstract

Summary: Hematopoietic stem and progenitor cell (HSPC) engraftment after transplantation during anticancer treatment depends on support from the recipient bone marrow (BM) microenvironment. Here, by studying physiological homing of fetal HSPCs, we show the critical requirement of balanced local crosstalk within the skeletal niche for successful HSPC settlement in BM. Transgene-induced overproduction of vascular endothelial growth factor (VEGF) by osteoprogenitor cells elicits stromal and endothelial hyperactivation, profoundly impacting the stromal-vessel interface and vascular architecture. Concomitantly, HSPC homing and survival are drastically impaired. Transcriptome profiling, flow cytometry, and high-resolution imaging indicate alterations in perivascular and endothelial cell characteristics, vascular function and cellular metabolism, associated with increased oxidative stress within the VEGF-enriched BM environment. Thus, developmental HSPC homing to bone is controlled by local stromal-vascular integrity and the oxidative-metabolic status of the recipient milieu. Interestingly, irradiation of adult mice also induces stromal VEGF expression and similar osteo-angiogenic niche changes, underscoring that our findings may contribute targets for improving stem cell therapies.

Published
2021
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4. SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells

Author

Juan Antonio García-León, Manoj Kumar, Ruben Boon, David Chau, Jennifer One, Esther Wolfs, Kristel Eggermont, Pieter Berckmans, Nilhan Gunhanlar, Femke de Vrij, Bas Lendemeijer, Benjamin Pavie, Nikky Corthout, Steven A. Kushner, José Carlos Dávila, Ivo Lambrichts, Wei-Shou Hu, and Catherine M. Verfaillie

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Summary: Scarce access to primary samples and lack of efficient protocols to generate oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering our understanding of OL biology and the development of novel therapies. Here, we demonstrate that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4+) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The SOX10-induced O4+ population resembles primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OL-neuron co-cultures, myelination of neurons by OLs can also be demonstrated, which can be adapted to a high-throughput screening format to test the response of pro-myelinating drugs. In conclusion, we provide an approach to generate OLs in a very rapid and efficient manner, which can be used for disease modeling, drug discovery efforts, and potentially for therapeutic OL transplantation. : In this article, García-León JA and colleagues demonstrate the generation of functional oligodendrocytes (OLs) from human pluripotent stem cells in a rapid and efficient manner by the single overexpression of SOX10. Generated OLs resemble primary OLs at the transcriptome level and can myelinate neurons both in vivo and in vitro. Neuron-OL co-cultures, adapted to high-throughput screening formats, responded to drugs affecting myelination. Keywords: oligodendrocyte, induced pluripotent stem cells (iPSCs), multiple sclerosis, amyotrophic lateral sclerosis, myelination, disease modeling, drug screening

Published
2018
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5. Generation of induced pluripotent stem cells from Chinese hamster embryonic fibroblasts

Author

Haiyun Pei, Hsu-Yuan Fu, Hiroyuki Hirai, Dong Seong Cho, Timothy D. O'Brien, James Dutton, Catherine M. Verfaillie, and Wei-Shou Hu

Subjects
Biology (General), QH301-705.5
Abstract

We derived a stable cell line from Chinese hamster embryonic fibroblasts by transduction of four mouse transcription factors (M3O, Sox2, Klf4, and n-Myc) using a lentiviral vector. The cell line possess all the characteristics of an induced pluripotent stem cell (iPSC) line. Given that Chinese hamster ovary (CHO) cells are the predominant host cells used for therapeutic protein production and no pluripotent stem cell line or other normal cell line has been isolated from Chinese hamster, this iPSC line may serve as a useful tool for research using CHO cells or even be used for deriving new cell lines.

Published
2017
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6. PDGFRα+ Cells in Embryonic Stem Cell Cultures Represent the In Vitro Equivalent of the Pre-implantation Primitive Endoderm Precursors

Author

Antonio Lo Nigro, Anchel de Jaime-Soguero, Rita Khoueiry, Dong Seong Cho, Giorgia Maria Ferlazzo, Ilaria Perini, Vanesa Abon Escalona, Xabier Lopez Aranguren, Susana M. Chuva de Sousa Lopes, Kian Peng Koh, Pier Giulio Conaldi, Wei-Shou Hu, An Zwijsen, Frederic Lluis, and Catherine M. Verfaillie

Subjects
embryonic stem cell heterogeneity, pre-implantation PrE precursors, in vitro model of early blastocyst development, PDGFRα+ subpopulations, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

In early mouse pre-implantation development, primitive endoderm (PrE) precursors are platelet-derived growth factor receptor alpha (PDGFRα) positive. Here, we demonstrated that cultured mouse embryonic stem cells (mESCs) express PDGFRα heterogeneously, fluctuating between a PDGFRα+ (PrE-primed) and a platelet endothelial cell adhesion molecule 1 (PECAM1)-positive state (epiblast-primed). The two surface markers can be co-detected on a third subpopulation, expressing epiblast and PrE determinants (double-positive). In vitro, these subpopulations differ in their self-renewal and differentiation capability, transcriptional and epigenetic states. In vivo, double-positive cells contributed to epiblast and PrE, while PrE-primed cells exclusively contributed to PrE derivatives. The transcriptome of PDGFRα+ subpopulations differs from previously described subpopulations and shows similarities with early/mid blastocyst cells. The heterogeneity did not depend on PDGFRα but on leukemia inhibitory factor and fibroblast growth factor signaling and DNA methylation. Thus, PDGFRα+ cells represent the in vitro counterpart of in vivo PrE precursors, and their selection from cultured mESCs yields pure PrE precursors.

Published
2017
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7. H3K27me3 Does Not Orchestrate the Expression of Lineage-Specific Markers in hESC-Derived Hepatocytes In Vitro

Author

Jolien Vanhove, Mariaelena Pistoni, Marc Welters, Kristel Eggermont, Veerle Vanslembrouck, Nicky Helsen, Ruben Boon, Mustapha Najimi, Etienne Sokal, Philippe Collas, J. Willem Voncken, and Catherine M. Verfaillie

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Although pluripotent stem cells can be differentiated into the hepatocyte lineages, such cells retain an immature phenotype. As the chromatin state of regulatory regions controls spatiotemporal gene expression during development, we evaluated changes in epigenetic histone marks in lineage-specific genes throughout in vitro hepatocyte differentiation from human embryonic stem cells (hESCs). Active acetylation and methylation marks at promoters and enhancers correlated with progressive changes in gene expression. However, repression-associated H3K27me3 marks at these control regions showed an inverse correlation with gene repression during transition from hepatic endoderm to a hepatocyte-like state. Inhibitor of Enhancer of Zeste Homolog 2 (EZH2) reduced H3K27me3 decoration but did not improve hepatocyte maturation. Thus, H3K27me3 at regulatory regions does not regulate transcription and appears dispensable for hepatocyte lineage differentiation of hESCs in vitro.

Published
2016
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8. Sodium Iodide Symporter PET and BLI Noninvasively Reveal Mesoangioblast Survival in Dystrophic Mice

Author

Bryan Holvoet, Mattia Quattrocelli, Sarah Belderbos, Lore Pollaris, Esther Wolfs, Olivier Gheysens, Rik Gijsbers, Jeroen Vanoirbeek, Catherine M. Verfaillie, Maurilio Sampaolesi, and Christophe M. Deroose

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Muscular dystrophies are a heterogeneous group of myopathies, characterized by muscle weakness and degeneration, without curative treatment. Mesoangioblasts (MABs) have been proposed as a potential regenerative therapy. To improve our understanding of the in vivo behavior of MABs and the effect of different immunosuppressive therapies, like cyclosporine A or co-stimulation-adhesion blockade therapy, on cell survival noninvasive cell monitoring is required. Therefore, cells were transduced with a lentiviral vector encoding firefly luciferase (Fluc) and the human sodium iodide transporter (hNIS) to allow cell monitoring via bioluminescence imaging (BLI) and small-animal positron emission tomography (PET). Non-H2 matched mMABs were injected in the femoral artery of dystrophic mice and were clearly visible via small-animal PET and BLI. Based on noninvasive imaging data, we were able to show that co-stim was clearly superior to CsA in reducing cell rejection and this was mediated via a reduction in cytotoxic T cells and upregulation of regulatory T cells.

Published
2015
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9. Efficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition

Author

Laura Ordovás, Ruben Boon, Mariaelena Pistoni, Yemiao Chen, Esther Wolfs, Wenting Guo, Rangarajan Sambathkumar, Sylwia Bobis-Wozowicz, Nicky Helsen, Jolien Vanhove, Pieter Berckmans, Qing Cai, Kim Vanuytsel, Kristel Eggermont, Veerle Vanslembrouck, Béla Z. Schmidt, Susanna Raitano, Ludo Van Den Bosch, Yaakov Nahmias, Toni Cathomen, Tom Struys, and Catherine M. Verfaillie

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Published
2018
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10. Efficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition

Author

Laura Ordovás, Ruben Boon, Mariaelena Pistoni, Yemiao Chen, Esther Wolfs, Wenting Guo, Rangarajan Sambathkumar, Sylwia Bobis-Wozowicz, Nicky Helsen, Jolien Vanhove, Pieter Berckmans, Qing Cai, Kim Vanuytsel, Kristel Eggermont, Veerle Vanslembrouck, Béla Z. Schmidt, Susanna Raitano, Ludo Van Den Bosch, Yaakov Nahmias, Toni Cathomen, Tom Struys, and Catherine M. Verfaillie

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Tools for rapid and efficient transgenesis in “safe harbor” loci in an isogenic context remain important to exploit the possibilities of human pluripotent stem cells (hPSCs). We created hPSC master cell lines suitable for FLPe recombinase-mediated cassette exchange (RMCE) in the AAVS1 locus that allow generation of transgenic lines within 15 days with 100% efficiency and without random integrations. Using RMCE, we successfully incorporated several transgenes useful for lineage identification, cell toxicity studies, and gene overexpression to study the hepatocyte lineage. However, we observed unexpected and variable transgene expression inhibition in vitro, due to DNA methylation and other unknown mechanisms, both in undifferentiated hESC and differentiating hepatocytes. Therefore, the AAVS1 locus cannot be considered a universally safe harbor locus for reliable transgene expression in vitro, and using it for transgenesis in hPSC will require careful assessment of the function of individual transgenes.

Published
2015
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11. Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways

Author

Javed K. Manesia, Zhuofei Xu, Dorien Broekaert, Ruben Boon, Alex van Vliet, Guy Eelen, Thomas Vanwelden, Steve Stegen, Nick Van Gastel, Alberto Pascual-Montano, Sarah-Maria Fendt, Geert Carmeliet, Peter Carmeliet, Satish Khurana, and Catherine M. Verfaillie

Subjects
Hematopoietic stem cells, Fetal liver, Bone marrow, Metabolism, Oxidative phosphorylation, Self-renewal, Biology (General), QH301-705.5
Abstract

Hematopoietic stem cells (HSCs) in the fetal liver (FL) unlike adult bone marrow (BM) proliferate extensively, posing different metabolic demands. However, metabolic pathways responsible for the production of energy and cellular building blocks in FL HSCs have not been described. Here, we report that FL HSCs use oxygen dependent energy generating pathways significantly more than their BM counterparts. RNA-Seq analysis of E14.5 FL versus BM derived HSCs identified increased expression levels of genes involved in oxidative phosphorylation (OxPhos) and the citric acid cycle (TCA). We demonstrated that FL HSCs contain more mitochondria than BM HSCs, which resulted in increased levels of oxygen consumption and reactive oxygen species (ROS) production. Higher levels of DNA repair and antioxidant pathway gene expression may prevent ROS-mediated (geno)toxicity in FL HSCs. Thus, we here for the first time highlight the underestimated importance of oxygen dependent pathways for generating energy and building blocks in FL HSCs.

Published
2015
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12. Restoration of Progranulin Expression Rescues Cortical Neuron Generation in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia

Author

Susanna Raitano, Laura Ordovàs, Louis De Muynck, Wenting Guo, Ira Espuny-Camacho, Martine Geraerts, Satish Khurana, Kim Vanuytsel, Balazs I. Tóth, Thomas Voets, Rik Vandenberghe, Toni Cathomen, Ludo Van Den Bosch, Pierre Vanderhaeghen, Philip Van Damme, and Catherine M. Verfaillie

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Summary: To understand how haploinsufficiency of progranulin (PGRN) causes frontotemporal dementia (FTD), we created induced pluripotent stem cells (iPSCs) from patients carrying the GRNIVS1+5G > C mutation (FTD-iPSCs). FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD. Although generation of neuroprogenitors was unaffected, their further differentiation into CTIP2-, FOXP2-, or TBR1-TUJ1 double-positive cortical neurons, but not motorneurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of GRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNA sequencing analysis confirmed reversal of the altered gene expression profile following genetic correction. We identified the Wnt signaling pathway as one of the top defective pathways in FTD-iPSC-derived neurons, which was reversed following genetic correction. Differentiation of FTD-iPSCs in the presence of a WNT inhibitor mitigated defective corticogenesis. Therefore, we demonstrate that PGRN haploinsufficiency hampers corticogenesis in vitro. : Verfaillie and colleagues describe the inefficient cortical neuron, but not motorneuron, generation, from FTD-patient-derived iPSCs carrying a mutation in the GRN gene. They show restoration of the defective phenotype following introduction of the GRN cDNA in FTD-iPSC using zinc finger nucleases and by inhibiting the WNT pathway.

Published
2015
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13. FANCA knockout in human embryonic stem cells causes a severe growth disadvantage

Author

Kim Vanuytsel, Qing Cai, Nisha Nair, Satish Khurana, Swati Shetty, Joris R. Vermeesch, Laura Ordovas, and Catherine M. Verfaillie

Subjects
Biology (General), QH301-705.5
Abstract

Fanconi anemia (FA) is an autosomal recessive disorder characterized by progressive bone marrow failure (BMF) during childhood, aside from numerous congenital abnormalities. FA mouse models have been generated; however, they do not fully mimic the hematopoietic phenotype. As there is mounting evidence that the hematopoietic impairment starts already in utero, a human pluripotent stem cell model would constitute a more appropriate system to investigate the mechanisms underlying BMF in FA and its developmental basis. Using zinc finger nuclease (ZFN) technology, we have created a knockout of FANCA in human embryonic stem cells (hESC). We introduced a selection cassette into exon 2 thereby disrupting the FANCA coding sequence and found that whereas mono-allelically targeted cells retain an unaltered proliferation potential, disruption of the second allele causes a severe growth disadvantage. As a result, heterogeneous cultures arise due to the presence of cells still carrying an unaffected FANCA allele, quickly outgrowing the knockout cells. When pure cultures of FANCA knockout hESC are pursued either through selection or single cell cloning, this rapidly results in growth arrest and such cultures cannot be maintained. These data highlight the importance of a functional FA pathway at the pluripotent stem cell stage.

Published
2014
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14. Altered osteo-angiogenic development of fetal endochondral bones impacts hematopoietic stem cell homing during embryogenesis and B cell production in postnatal life

Author

Manmohan Bajaj, Christa Maes, Marion Mesnieres, Anna-Marei Böhm, Satish Khurana, Pieter Baatsen, Nicolas Peredo, and Catherine M. Verfaillie

Subjects
Fetus, lcsh:Diseases of the musculoskeletal system, Endocrinology, Diabetes and Metabolism, Embryogenesis, Hematopoietic stem cell, Biology, Cell biology, medicine.anatomical_structure, medicine, Orthopedics and Sports Medicine, lcsh:RC925-935, Endochondral ossification, B cell, Homing (hematopoietic)
Published
2020

15. PDGFRα+ Cells in Embryonic Stem Cell Cultures Represent the In Vitro Equivalent of the Pre-implantation Primitive Endoderm Precursors

Author

Susana M. Chuva de Sousa Lopes, Pier Giulio Conaldi, Anchel de Jaime-Soguero, Frederic Lluis, Antonio Lo Nigro, Vanesa Abon Escalona, Ilaria Perini, An Zwijsen, Xabier L. Aranguren, Wei Shou Hu, Rita Khoueiry, Catherine M. Verfaillie, Dong Seong Cho, Kian Peng Koh, and Giorgia Maria Ferlazzo

Subjects
0301 basic medicine, Receptor, Platelet-Derived Growth Factor alpha, Cellular differentiation, Embryonic Development, Biology, Fibroblast growth factor, Biochemistry, Article, Cell Line, Epigenesis, Genetic, 03 medical and health sciences, Mice, 0302 clinical medicine, Growth factor receptor, Genetics, medicine, Angiopoietin-1, Animals, pre-implantation PrE precursors, Blastocyst, embryonic stem cell heterogeneity, lcsh:QH301-705.5, Cells, Cultured, Embryonic Stem Cells, lcsh:R5-920, Endoderm, Gene Expression Regulation, Developmental, Cell Differentiation, Cell Biology, DNA Methylation, in vitro model of early blastocyst development, Embryonic stem cell, Cell biology, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), Epiblast, Immunology, PDGFRα+ subpopulations, lcsh:Medicine (General), Leukemia inhibitory factor, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology, Signal Transduction
Abstract

Summary In early mouse pre-implantation development, primitive endoderm (PrE) precursors are platelet-derived growth factor receptor alpha (PDGFRα) positive. Here, we demonstrated that cultured mouse embryonic stem cells (mESCs) express PDGFRα heterogeneously, fluctuating between a PDGFRα+ (PrE-primed) and a platelet endothelial cell adhesion molecule 1 (PECAM1)-positive state (epiblast-primed). The two surface markers can be co-detected on a third subpopulation, expressing epiblast and PrE determinants (double-positive). In vitro, these subpopulations differ in their self-renewal and differentiation capability, transcriptional and epigenetic states. In vivo, double-positive cells contributed to epiblast and PrE, while PrE-primed cells exclusively contributed to PrE derivatives. The transcriptome of PDGFRα+ subpopulations differs from previously described subpopulations and shows similarities with early/mid blastocyst cells. The heterogeneity did not depend on PDGFRα but on leukemia inhibitory factor and fibroblast growth factor signaling and DNA methylation. Thus, PDGFRα+ cells represent the in vitro counterpart of in vivo PrE precursors, and their selection from cultured mESCs yields pure PrE precursors., Graphical Abstract, Highlights • Three subpopulations can be purified from mESC cultures by using PECAM1 and PDGFRα • Expression of PDGFRα is associated with a molecular and epigenetic PrE signature • PDGFRα+ cells are committed toward PrE derivatives in vitro and in vivo, In this article, Lo Nigro and colleagues further dissect the heterogeneity of mESC cultures by using the endogenous and heterogeneous expression of PECAM1 and PDGFRα. By combining the expression of these surface markers, the authors describe a strategy to sort out a subpopulation that exclusively gives rise to extraembryonic endodermal derivatives in vitro and in vivo.

Published
2017

17. The Development and Application of Key Technologies and Tools

Author

Tuula Heinonen and Catherine M. Verfaillie

Subjects
Systems toxicology, Risk analysis (engineering), Laboratory animal welfare, Cellular differentiation, Key (cryptography), Public concern, Business, Stem cell, Induced pluripotent stem cell, Omics technologies
Abstract

An interest in understanding the cellular and molecular mechanisms behind biological processes, and diseases, and the toxicity of chemicals, and the need to develop effective pharmaceuticals, have been the key drivers for the development of cellular models and related technologies. Public concern about laboratory animal welfare and the recognition that animals and humans have substantial physiological differences have also encouraged and promoted the shift from animal-based tests toward human-based cell, organ and tissue models. In Europe, the European Commission has been one of the key players. The standardised production of human stem cells and induced human pluripotent cell-based differentiated cells with human in vivo-like properties has, and will be, a key factor, in addition to other key technologies, e.g. in relation to biomaterials and culture media, in developing adequate models. A very important milestone and promoter for cellular models was the mapping of all the genes of the human genome, which, via the development of omics technologies, helped to increase understanding of the biological processes behind normal functions, adverse effects and diseases. This has also laid the basis for systems toxicology-based risk assessment.

Published
2019

18. Contributors

Author

Rachit Agarwal, Jon D. Ahlstrom, Rafiq Ahmad, Emilio I. Alarcon, Alejandro J. Almarza, Graça Almeida-Porada, Manuel Almeida, Melissa Alvarado-Velez, James M. Anderson, Judith Arcidiacono, Anthony Atala, Stephen F. Badylak, Wayne Balkan, Brian G. Ballios, Pedro M. Baptista, M. Douglas Baumann, Supinder S. Bedi, Ravi V. Bellamkonda, Nicole M. Bergmann, Helen M. Blau, Joel D. Boerckel, Andres M. Bratt-Leal, James C. Brown, Scott Brubaker, Isabelle Brunette, Gisele A. Calderon, Arnold I. Caplan, David G. Castner, Cynthia Chang, Aditya Chawla, Xuguang Chen, Paul Cohen, Michael J. Cooke, Joshua S. Copus, Vitor M. Correlo, Charles S. Cox, Abritee Dahl, Richard M. Day, Paolo De Coppi, Mahesh C. Dodla, Jennifer H. Elisseeff, Juliet A. Emamaullee, Adam Esa, Yunlan Fang, Heather J. Faust, John P. Fisher, Matthew B. Fisher, Elvis L. Francois, Andrés J. García, Svetlana Gavrilov, Dan Gazit, Zulma Gazit, Christopher V. Gemmiti, Gregory J. Gillispie, Sarah E. Gilpin, W.T. Godbey, Andrea Gray, Ronald M. Green, May Griffith, Robert E. Guldberg, Qiongyu Guo, Geoffrey C. Gurtner, Michael C. Hacker, Issa A. Hanna, Joshua M. Hare, Konstantinos E. Hatzistergos, Ralf-Peter Herber, Jöns Hilborn, H. David Humes, Joshua G. Hunsberger, Kenjiro Iwasa, John D. Jackson, Margaret L. Jackson, Hae Lin Jang, John A. Jansen, Josephine Johnston, Carl Jorns, Huijun Kang, David L. Kaplan, David S. Kaplan, Adam J. Katz, Matthew W. Kelley, Kelsey Kennedy, Ali Khademhosseini, Gilson Khang, Jinho Kim, Rachel H. Klein, Irina Klimanskaya, Paul S. Knoepfler, In Kap Ko, Yash M. Kolambkar, Jan Krieghoff, Nathan W. Kucko, Manoj Kumar, Joanne Kurtzberg, Anna Kwilas, Donald W. Landry, Mark T. Langhans, Robert Lanza, Giacomo Lanzoni, Sang Jin Lee, Sander C.G. Leeuwenburgh, Kam W. Leong, Rui Liang, Volha Liaudanskaya, Hang Lin, Michael T. Longaker, Hermann P. Lorenz, Jeanne F. Loring, Shi-Jiang Lu, Alberto Lue, Peter X. Ma, Renata S. Magalhaes, Serena Mandla, Clement D. Marshall, Manuela Martins-Green, Devon E. Mason, Jonquil R. Mau, Richard McFarland, Melissa K. McHale, James C. Melville, Jason R. Meyers, Antonios G. Mikos, Jordan S. Miller, Paul A. Mittermiller, Hideki Miyachi, Shinka Miyamoto, Nelson Monteiro, Alessandra L. Moore, Sara Morini, Philipp T. Moser, Vivek J. Mukhatyar, Mark Murdock, Aaron Nagiel, Gail K. Naughton, Allison Nauta, Javier Navarro, Jared M. Newton, Aparna Nori, Teruo Okano, Joaquim M. Oliveira, Harald C. Ott, Jagannath Padmanabhan, Kristin M. Page, Anil Kumar Pallickaveedu Rajan Asari, Virginia E. Papaioannou, Jihoon Park, Samantha L. Payne, Gadi Pelled, Andrew Pepper, Elumalai Perumal, Melissa Petreaca, Christopher J. Pino, Alessandro Pirosa, Iris Pla-Palacín, Marta Pokrywczynska, Christopher D. Porada, Blaise D. Porter, Milica Radisic, Kunal J. Rambhia, F. Raquel Maia, Buddy D. Ratner, A.H. Reddi, Rui L. Reis, Laura Ricles, Camillo Ricordi, Muhammad Rizwan, Rebecca Robinson, Melanie Rodrigues, Benjamin B. Rothrauff, Hooman Sadri-Ardekani, Pilar Sainz-Arnal, Rangarajan Sambathkumar, Natalia Sánchez-Romero, Michelle Scarritt, Christopher M. Schneider, Steven D. Schwartz, Sarah Selem, Trinidad Serrano-Aulló, A.M. James Shapiro, Dmitriy Sheyn, Tatsuya Shimizu, Toshiharu Shinoka, Molly S. Shoichet, Toshihiro Shoji, Thomas Shupe, Andrew G. Sikora, Fiona Simpson, Aleksander Skardal, Daniel Skuk, Brandon T. Smith, Jihee Sohn, Shay Soker, Estela Solanas, Jeong Eun Song, Disha Sood, David L. Stocum, Stephen C. Strom, Jessica M. Sun, Hironobu Takahashi, Jacques P. Tremblay, Nirmalya Tripathy, John W. Tse, Rocky S. Tuan, Catherine M. Verfaillie, Gordana Vunjak-Novakovic, William R. Wagner, Yanling Wang, Emma Watson, Jennifer L. West, David F. Williams, James K. Williams, Mark E. Wong, Savio L-Y. Woo, Fiona M. Wood, Lei Xu, Doron C. Yakubovich, Yafeng Yang, Michael J. Yaszemski, Pamela C. Yelick, Evelyn K.F. Yim, Carolyn Yong, James J. Yoo, Simon Young, Nora Yucel, Rachel L. Zacharias, Yuanyuan Zhang, Ai Zhang, Jin Zhang, and Yang Zhu

Published
2018

19. Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways

Author

Alberto Pascual-Montano, Guy Eelen, Alexander R. van Vliet, Geert Carmeliet, Catherine M. Verfaillie, Zhuofei Xu, Steve Stegen, Nick van Gastel, Sarah-Maria Fendt, Satish Khurana, Thomas Vanwelden, Dorien Broekaert, Javed Karim Manesia, Ruben Boon, and Peter Carmeliet

Subjects
DNA repair, Oxidative phosphorylation, Mitochondrion, Biology, Fetus, medicine, Humans, Bone marrow, lcsh:QH301-705.5, Cells, Cultured, chemistry.chemical_classification, Medicine(all), Reactive oxygen species, hemic and immune systems, General Medicine, Cell Biology, Cell biology, Haematopoiesis, Metabolic pathway, Fetal liver, medicine.anatomical_structure, Metabolism, Biochemistry, chemistry, Liver, lcsh:Biology (General), Self-renewal, Stem cell, Metabolic Networks and Pathways, Hematopoietic stem cells, Developmental Biology
Abstract

Hematopoietic stem cells (HSCs) in the fetal liver (FL) unlike adult bone marrow (BM) proliferate extensively, posing different metabolic demands. However, metabolic pathways responsible for the production of energy and cellular building blocks in FL HSCs have not been described. Here, we report that FL HSCs use oxygen dependent energy generating pathways significantly more than their BM counterparts. RNA-Seq analysis of E14.5 FL versus BM derived HSCs identified increased expression levels of genes involved in oxidative phosphorylation (OxPhos) and the citric acid cycle (TCA). We demonstrated that FL HSCs contain more mitochondria than BM HSCs, which resulted in increased levels of oxygen consumption and reactive oxygen species (ROS) production. Higher levels of DNA repair and antioxidant pathway gene expression may prevent ROS-mediated (geno)toxicity in FL HSCs. Thus, we here for the first time highlight the underestimated importance of oxygen dependent pathways for generating energy and building blocks in FL HSCs. publisher: Elsevier articletitle: Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways journaltitle: Stem Cell Research articlelink: http://dx.doi.org/10.1016/j.scr.2015.11.001 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier B.V. ispartof: Stem Cell Research vol:15 issue:3 pages:715-21 ispartof: location:England status: published

Published
2015

20. Restoration of Progranulin Expression Rescues Cortical Neuron Generation in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia

Author

Rik Vandenberghe, Thomas Voets, Satish Khurana, Philip Van Damme, Kim Vanuytsel, Wenting Guo, Louis De Muynck, Laura Ordovás, Catherine M. Verfaillie, Toni Cathomen, Martine Geraerts, Susanna Raitano, Ira Espuny-Camacho, Pierre Vanderhaeghen, Ludo Van Den Bosch, and Balázs István Tóth

Subjects
Génétique du développement, Time Factors, Transcription, Genetic, Cellular differentiation, Gene Expression, Haploinsufficiency, Biochemistry, Progranulins, Neural Stem Cells, Elméleti orvostudományok, Induced pluripotent stem cell, Wnt Signaling Pathway, lcsh:QH301-705.5, Neurons, Genetics, lcsh:R5-920, Neurogenesis, Wnt signaling pathway, Cell Differentiation, Orvostudományok, Neural stem cell, Cell biology, Microbiologie et protistologie [entomologie,phytoparasitolog.], Corticogenesis, Phenotype, Frontotemporal Dementia, Intercellular Signaling Peptides and Proteins, lcsh:Medicine (General), Frontotemporal dementia, Microbiologie et protistologie [parasitologie hum. et anim.], Biochimie, Induced Pluripotent Stem Cells, Biology, Cell Line, Report, mental disorders, medicine, Humans, Gene Expression Profiling, nutritional and metabolic diseases, Cell Biology, medicine.disease, nervous system diseases, lcsh:Biology (General), Mutation, Biologie cellulaire, Transcriptome, Microbiologie et protistologie [bacteriol.virolog.mycolog.], Biomarkers, Developmental Biology
Abstract

Summary To understand how haploinsufficiency of progranulin (PGRN) causes frontotemporal dementia (FTD), we created induced pluripotent stem cells (iPSCs) from patients carrying the GRNIVS1+5G > C mutation (FTD-iPSCs). FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD. Although generation of neuroprogenitors was unaffected, their further differentiation into CTIP2-, FOXP2-, or TBR1-TUJ1 double-positive cortical neurons, but not motorneurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of GRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNA sequencing analysis confirmed reversal of the altered gene expression profile following genetic correction. We identified the Wnt signaling pathway as one of the top defective pathways in FTD-iPSC-derived neurons, which was reversed following genetic correction. Differentiation of FTD-iPSCs in the presence of a WNT inhibitor mitigated defective corticogenesis. Therefore, we demonstrate that PGRN haploinsufficiency hampers corticogenesis in vitro., Graphical Abstract, Highlights • In vitro generation of cortical neurons from PGRN deficient FTD-iPSC is inefficient • Incorporation of GRN cDNA via ZFN technology rescues cortical neurons generation • WNT signaling may also play a major role in the defects observed, Verfaillie and colleagues describe the inefficient cortical neuron, but not motorneuron, generation, from FTD-patient-derived iPSCs carrying a mutation in the GRN gene. They show restoration of the defective phenotype following introduction of the GRN cDNA in FTD-iPSC using zinc finger nucleases and by inhibiting the WNT pathway.

Published
2015

21. Stem cells in neurodegeneration: mind the gap

Author

Catherine M. Verfaillie, Christel Claes, and Joke Terryn

Subjects
Transplantation, Cell therapy, Neurodegeneration, medicine, Disease, Biology, Stem cell, medicine.disease, Neuroscience
Abstract

Stem cell technology has opened new opportunities to crack neurodegeneration. Stem cell therapies are being developed to replace the lost neuronal tissue. The major questions in cell transplantation will be addressed, guided by examples of trials conducted in Parkinson’s and Alzheimer’s disease. In addition, we will elaborate on stem cell models, as they are ideally suited for disease modeling and drug screening. Disease modeling complements cell therapy, as it aids in the development of therapies for neurodegeneration.

Published
2017

22. List of Contributors

Author

Matthew Bird, Christel Claes, Mark R. Cookson, Marc Cruts, Nicole Déglon, Marion Delenclos, Ilse Dewachter, Richard Gordon, Sarah Libbrecht, Pamela J. McLean, Ronald Melki, Simon Moussaud, Tiago F. Outeiro, Wouter Peelaerts, Kristel Sleegers, Ilie-Cosmin Stancu, Joke Terryn, Dick Terwel, Christine Van Broeckhoven, Ludo Van Den Bosch, Bruno Vasconcelos, Catherine M. Verfaillie, Eline Wauters, and Trent M. Woodruff

Published
2017

23. Multipotent Adult Progenitor Cells (MAPCs) for Cardiovascular and Neurologic Diseases

Author

Philip Roelandt, Valerie D. Roobrouck, and Catherine M. Verfaillie

Subjects
Transplantation, Paracrine signalling, Regeneration (biology), Mesenchymal stem cell, Immunology, medicine, Disease, Progenitor cell, Biology, medicine.disease, Stroke, Inflammatory bowel disease
Abstract

Multipotent adult progenitor cells (MAPCs) are isolated from bone marrow-derived mesenchymal stem cell cultures. Human MAPCs (commercially available as a clinical-grade product termed MultiStem®) possess the capacity to be expanded long term; however, the differentiation potential of human MAPC is restricted mainly to the mesodermal lineage. Both rodent and human MAPCs have been shown to be effective in improving outcome of preclinical models of ischemic cardiac, vascular and neurological diseases, where the mechanism of action is mainly via trophic, cytoprotective, and/or immunomodulatory effects, as actual cellular replacement is rare. Human MAPCs are currently being evaluated in a number of phase I/II clinical trials in patients with stroke, acute myocardial infarction (AMI), inflammatory bowel disease (IBD), and in patients undergoing BM transplantation for the prevention of acute graft-versus-host disease (GvHD).

Published
2016

24. List of Contributors

Author

Deborah D. Ascheim, Wayne Balkan, Akshay Bareja, Courtney E. Bartlett, Atta Behfar, Lisle Blackbourn, Roberto Bolli, L. Maximilian Buja, Angela Castellanos, Antoine H. Chaanine, Eric Chau, Zhen Chen, Karen L. Christman, Amy Chung, Robert M. Cole, John P. Cooke, H.J. Duckers, Victor J. Dzau, Ray F. Ebert, Jun Fujita, Keiichi Fukuda, Roberto Gaetani, Amir Gahremanpour, W. Gathier, Annetine C. Gelijns, Andrea S. Gobin, José A. Gomez, Roger J. Hajjar, Joshua M. Hare, Nirmala Hariharan, Timothy D. Henry, William Hiesinger, Alan T. Hirsch, Conrad P. Hodgkinson, Kimberly N. Hong, Kyung U. Hong, Thomas E. Ichim, E. Marc Jolicoeur, Kazuki Kodo, Sandeep K. Krishnan, Michael J.B. Kutryk, David S. Lee, Randall J. Lee, Douglas W. Losordo, Elton Migliati, Leslie W. Miller, Vivek Misra, Lem Moyé, Nathalie Nguyen, Sang-Ging Ong, Aaron Orozco, Amit N. Patel, Brittany M. Penn, Marc S. Penn, Emerson C. Perin, Amish N. Raval, Micheline Resende, Philip R. Roelandt, Valerie D. Roobrouck, Luiz C. Sampaio, Sean I. Savitz, Eric G. Schmuck, Ivonne Hernandez Schulman, Robert D. Simari, Luis Felipe Silva Smidt, Rachel Ruckdeschel Smith, Duncan J. Stewart, Mark A. Sussman, Deephak Swaminath, Sabrina Taldone, Doris A. Taylor, Andre Terzic, Jay H. Traverse, Z. Türktaş, Jessica Ungerleider, Deborah Vela, Catherine M. Verfaillie, Bojan Vrtovec, Thomas Weber, Y. Joseph Woo, James T. Willerson, Joseph C. Wu, Alex Yaroshinsky, Lior Zangi, and Jianyi (Jay) Zhang

Published
2016

25. Multipotent Adult Progenitor Cells

Author

Valerie D. Roobrouck, Catherine M. Verfaillie, and Philip Roelandt

Subjects
urogenital system, Ectoderm, Germ layer, Embryoid body, Biology, Embryonic stem cell, Cell biology, medicine.anatomical_structure, embryonic structures, medicine, biological phenomena, cell phenomena, and immunity, Progenitor cell, Endoderm, Induced pluripotent stem cell, reproductive and urinary physiology, Adult stem cell
Abstract

Embryonic stem cells (ESCs) are pluripotent stem cells, because they can be propagated indefinitely, and differentiate into cells of all three germ layers (endoderm, mesoderm, and ectoderm), shown by teratoma and embryoid body (EB) formation. Following blastocyst injection, mouse ESCs contribute to all somatic and germ-line lineages. ESCs are derived from the inner cell mass (ICM) of the blastocyst and are true pluripotent stem cells. Oct4 is expressed in the pre-gastrulation embryo, primordial germ cells, the ICM, and germ cells. While normal expression levels of Oct4 maintain mouse ESC self-renewal, a decrease in expression to 200% to primitive endoderm differentiation. In recent years more and more has become known about what regulates the expression of Oct4.

Published
2014

26. List of Contributors

Author

Russell C. Addis, Piero Anversa, Judith Arcidiacono, Anthony Atala, Joyce Axelman, Ashok Batra, Helen M. Blau, Susan Bonner-Weir, Mairi Brittan, Hal E. Broxmeyer, Mara Cananzi, Constance Cepko, Tao Cheng, Susana M. Chuva de Sousa Lopes, Gregory O. Clark, Maegen Colehour, Paolo de Coppi, Giulio Cossu, George Q. Daley, Jiyoung M. Dang, Natalie Direkze, Yuval Dor, Gregory R. Dressler, Charles N. Durfor, Ewa C.S. Ellis, Martin Evans, Donna M. Fekete, Donald Fink, Elaine Fuchs, Margaret T. Fuller, Richard L. Gardner, Zulma Gazit, Dan Gazit, John D. Gearhart, Victor M. Goldberg, Rodolfo Gonzalez, Deborah Lavoie Grayeski, Ronald M. Green, Markus Grompe, Stephen L. Hilbert, Marko E. Horb, Jerry I. Huang, Jaimie Imitola, D. Leanne Jones, Jan Kajstura, David S. Kaplan, Pritinder Kaur, Kathleen C. Kent, Candace L. Kerr, Ali Khademhosseini, Nadav Kimelman, Irina Klimanskaya, Jennifer N. Kraszewski, Mark A. LaBarge, Robert Langer, Robert Lanza, Ellen Lazarus, Jean Pyo Lee, Mark H. Lee, Annarosa Leri, Shulamit Levenberg, S. Robert Levine, John W. Littlefield, Richard McFarland, Jill McMahon, Douglas A. Melton, Mary Tyler Moore, Franz-Josef Mueller, Christine L. Mummery, Bernardo Nadal-Ginard, Hitoshi Niwa, Keisuke Okita, Jitka Ourednik, Vaclav Ourednik, Kook I. Park, Ethan S. Patterson, Gadi Pelled, Christopher S. Potten, Sean Preston, Philip R. Roelandt, Valerie D. Roobrouck, Nadia Rosenthal, Janet Rossant, Maurilio Sampaolesi, Maria Paola Santini, David T. Scadden, Holger Schlüter, Gunter Schuch, Michael J. Shamblott, Dima Sheyn, Richard L. Sidman, Evan Y. Snyder, Shay Soker, Stephen C. Strom, Lorenz Studer, M. Azim Surani, Francesco Saverio Tedesco, Yang D. Teng, David Tosh, Alan Trounson, Tudorita Tumbar, Edward Upjohn, George Varigos, Catherine M. Verfaillie, Zhan Wang, Gordon C. Weir, Kevin J. Whittlesey, J. Koudy Williams, James W. Wilson, Celia Witten, Nicholas A. Wright, Shinya Yamanaka, and Jung U. Yoo

Published
2014

27. Contributors

Author

Piero Anversa, Judith Arcidiacono, Anthony Atala, Yann Barrandon, Ashok Batra, Daniel Becker, Nicole M. Bergmann, Paolo Bianco, Helen M. Blau, Susan Bonner-Weir, Mairi Brittan, Hal E. Broxmeyer, Mara Cananzi, Arnold I. Caplan, Constance Cepko, Maegen Colehour, Giulio Cossu, George Q. Daley, Jiyoung M. Dang, Ayelet Dar, Brian R. Davis, Paolo de Coppi, Natalie Direkze, Juan Domínguez-Bendala, Yuval Dor, Gregory R. Dressler, Charles N. Durfor, Rita B. Effros, Ewa C.S. Ellis, Margaret A. Farley, Donna M. Fekete, Qiang Feng, Donald Fink, Elaine Fuchs, Dan Gazit, Zulma Gazit, Sharon Gerecht, Victor M. Goldberg, Rodolfo Gonzalez, François Gorostidi, Elizabeth Gould, Nicolas Grasset, Deborah Lavoie Grayeski, Ronald M. Green, Markus Grompe, Joshua M. Hare, Konstantinos E. Hatzistergos, Kevin E. Healy, Stephen L. Hilbert, Jerry I. Huang, James Huettner, Jaimie Imitola, Elizabeth F. Irwin, Joseph Itskovitz-Eldor, Josephine Johnston, Jan Kajstura, David S. Kaplan, Adam J. Katz, Pritinder Kaur, Erin A. Kimbrel, Nadav Kimelman, Chris Kintner, Naoko Koyano-Nakagawa, Tilo Kunath, Mark A. LaBarge, Robert Lanza, Stéphanie Lathion, Ellen Lazarus, Jean Pyo Lee, Mark H. Lee, Annarosa Leri, S. Robert Levine, Feng Li, Shi-Jiang Lu, John W. McDonald, Richard McFarland, Melissa K. McHale, Douglas A. Melton, Alexander F. Mericli, Christian Mirescu, Malcolm A.S. Moore, Mary Tyler Moore, Franz-Josef Mueller, Bernardo Nadal-Ginard, Jitka Ourednik, Vaclav Ourednik, Kook I. Park, Gadi Pelled, Antonello Pileggi, Jacob F. Pollock, Christopher S. Potten, Sean Preston, Nicole L. Prokopishyn, Camillo Ricordi, Pamela Gehron Robey, Ariane Rochat, Philip R. Roelandt, Valerie D. Roobrouck, Nadia Rosenthal, Janet Rossant, Maurilio Sampaolesi, Maria Paola Santini, David V. Schaffer, Holger Schlüter, Gunter Schuch, Sarah Selem, Dima Sheyn, Richard L. Sidman, Daniel Skuk, Evan Y. Snyder, Shay Soker, Stephen C. Strom, Lorenz Studer, Francesco Saverio Tedesco, Yang D. Teng, Jacques P. Tremblay, Tudorita Tumbar, Edward Upjohn, George Varigos, Catherine M. Verfaillie, Zhan Wang, Gordon C. Weir, Jennifer L. West, Kevin J. Whittlesey, J. Koudy Williams, J.W. Wilson, Celia Witten, Nicholas A. Wright, and Jung U. Yoo

Published
2013

28. Neural differentiation and support of neuroregeneration of non-neural adult stem cells

Author

Rojin Abraham and Catherine M. Verfaillie

Subjects
Neuroepithelial cell, Neurosphere, Neurogenesis, Clinical uses of mesenchymal stem cells, Amniotic stem cells, Biology, Stem cell, Neuroscience, Neural stem cell, Adult stem cell
Abstract

Although it is well established that neural stem cells (NSCs) or neural stem/progenitor cells differentiated from pluripotent stem cells can generate neurons, astrocytes, and oligodendrocytes, a number of other cell populations are also being considered for therapy of central nervous system disorders. Here, we describe the potential of (stem) cells from other postnatal tissues, including bone marrow, (umbilical cord) blood, fat tissue, or dental pulp, which themselves do not (robustly) generate neural progeny. However, these non-neuroectoderm derived cell populations appear to capable of inducing endogenous neurogenesis and angiogenesis. As these "trophic" effects are also, at least partly, responsible for some of the beneficial effects seen when NSC are grafted in the brain, these non-neuroectodermal cells may exert beneficial effects when used to treat neurodegenerative disorders.

Published
2012

29. Regulation of hematopoiesis

Author

Shannon Buckley and Catherine M. Verfaillie

Subjects
Haematopoiesis, Biology, Cell biology
Published
2011

30. Contributors

Author

Tamer Aboushwareb, Jon D. Ahlstrom, Alejandro J. Almarza, James M. Anderson, Judith Arcidiacono, Anthony Atala, Stephen F. Badylak, Jae Hyun Bae, Brian G. Ballios, Ashok Batra, M. Douglas Baumann, Ravi V. Bellamkonda, Nicole M. Bergmann, Mickie Bhatia, Martin A. Birchall, Helen M. Blau, Joel D. Boerckel, Ali H. Brivanlou, Mara Cananzi, Arnold I. Caplan, Joseph W. Carnwath, Grant A. Challen, George J. Christ, Hyun Jung Chung, Maegen Colehour, Michael J. Cooke, V.M. Correlo, Benjamin D. Cosgrove, Stefano Da Sacco, Jiyoung M. Dang, Richard M. Day, Paolo De Coppi, Roger E. De Filippo, Mahesh C. Dodla, Juan Domínguez-Bendala, Ryan P. Dorin, Charles N. Durfor, Rita B. Effros, Jennifer H. Elisseeff, Ewa C.S. Ellis, Juliet A. Emamaullee, Per Fagerholm, Qiang Feng, Donald Fink, Matthew B. Fisher, Andrés J. García, Svetlana Gavrilov, Dan Gazit, Zulma Gazit, Christopher V. Gemmiti, Charles A. Gersbach, Margaret A. Goodell, Deborah Lavoie Grayeski, Ronald M. Green, May Griffith, Robert E. Guldberg, Qiongyu Guo, M.C. Hacker, Joanne Hackett, Joshua M. Hare, Benjamin S. Harrison, Konstantinos E. Hatzistergos, Kevin E. Healy, Stephen L. Hilbert, Jiang Hu, Alexander Huber, H. David Humes, Elizabeth F. Irwin, Brett C. Isenberg, Takanori Iwata, Sam Janes, Lily Jeng, Junfeng Ji, Josephine Johnston, Kimberly A. Johnston, David L. Kaplan, David S. Kaplan, Sinan Karaoglu, Adam J. Katz, Jaehyun Kim, Erin A. Kimbrel, Nadav Kimelman, Jonathan A. Kluge, Chester J. Koh, Yash M. Kolambkar, Makoto Komura, Wilfried A. Kues, Francois Ng kee Kwong, Neil Lagali, Deepak A. Lamba, Donald W. Landry, Robert Lanza, Barrett Larson, Malcolm A. Latorre, Ellen Lazarus, Hyukjin Lee, Mark H. Lee, Sang Jin Lee, Gary G. Leisk, Feng Li, Rui Liang, Kuanyin K. Lin, Xiaohua Liu, Michael T. Longaker, H. Peter Lorenz, Shi-Jiang Lu, Andrea Lucas-Hahn, Peter X. Ma, Paolo Macchiarini, Masood A. Machingal, J.F. Mano, M. Martins-Green, Michael McCall, Richard McFarland, Melissa K. McHale, Alexander F. Mericli, A.G. Mikos, Vivek J. Mukhatyar, Allison Nauta, N.M. Neves, Heiner Niemann, Teruo Okano, Keisuke Okita, J.M. Oliveira, Virginia E. Papaioannou, Tae Gwan Park, Gadi Pelled, Laura Perin, M. Petreaca, Antonello Pileggi, Jacob F. Pollock, Blaise D. Porter, Milica Radisic, Nandini Rao, A.H. Reddi, Thomas A. Reh, R.L. Reis, Camillo Ricordi, Philip Roelandt, Caroline Beth Sangan, Justin M. Saul, David V. Schaffer, Gunter Schuch, Michael V. Sefton, Sarah Selem, A.M. James Shapiro, Heather Sheardown, Dima Sheyn, Molly S. Shoichet, Harvir Singh, Sirinrath Sirivisoot, Daniel Skuk, Shay Soker, Myron Spector, David L. Stocum, Stephen C. Strom, James A. Thomson, David Tosh, Robert T. Tranquillo, Jacques P. Tremblay, Catherine M. Verfaillie, Zhan Wang, Jennifer L. West, Kevin J. Whittlesey, Chrysanthi Williams, David F. Williams, J. Koudy Williams, Celia Witten, Savio L.-Y. Woo, Fiona Wood, Shinya Yamanaka, Masayuki Yamato, Saami K. Yazdani, James J. Yoo, Junying Yu, and Bonan Zhong

Published
2011

31. Stem Cells

Author

Rikkert L. Snoeckx, Kris Van Den Bogaert, and Catherine M. Verfaillie

Subjects
Biology, Stem cell, Cell biology
Published
2009

32. Contributors

Author

Russell C. Addis, Michal Amit, Peter W. Andrews, Piero Anversa, Anthony Atala, Joyce Axelman, Anne G. Bang, Yann Barrandon, Steven R. Bauer, Daniel Becker, Nissim Benvenisty, Paolo Bianco, Helen M. Blau, Susan Bonner-Weir, Mairi Brittan, Hal E. Broxmeyer, Scott Bultman, Arnold I. Caplan, Melissa K. Carpenter, Fatima Cavaleri, Connie Cepko, Howard Y. Chang, Xin Chen, Tao Cheng, Susana M. Chuva de Sousa Lopes, Gregory O. Clark, Michael F. Clarke, Giulio Cossu, Annelies Crabbe, George Q. Daley, Ayelet Dar, Brian R. Davis, Natalie C. Direkze, Yuval Dor, Jonathan S. Draper, Gregory R. Dressler, Martin Evans, Margaret A. Farley, Donna Fekete, Qiang Feng, Loren J. Field, Donald W. Fink, K. Rose Finley, Elaine Fuchs, Margaret T. Fuller, Richard L. Gardner, John D. Gearhart, Pamela Gehro. Robey, Sharon Gerecht-Nir, Penney M. Gilbert, Victor M. Goldberg, Rodolfo Gonzalez, Elizabeth Gould, Trevor A. Graham, Ronald M. Green, Markus Grompe, Dirk Hockemeyer, Marko E. Horb, Jerry I. Huang, Adam Humphries, Joseph Itskovitz-Eldor, Rudolf Jaenisch, Penny Johnson, D. Leanne Jones, Jan Kajstura, Gerard Karsenty, Pritinder Kaur, Kathleen C. Kent, Candace L. Kerr, Ali Khademhosseini, Chris Kintner, Irina Klimanskaya, Naoko Koyano-Nakagawa, Jennifer N. Kraszewski, Tilo Kunath, Robert Langer, Robert Lanza, Annarosa Leri, Shulamit Levenberg, S. Robert Levine, Olle Lindvall, John W. Littlefield, Shi-Jiang Lu, Terry Magnuson, Yoav Mayshar, John W. McDonald, Stuart A.C. McDonald, Anne McLaren, Jill McMahon, Douglas A. Melton, Christian Mirescu, Nathan Montgomery, Malcolm A.S. Moore, Mary Tyle. Moore, Christine L. Mummery, Andras Nagy, Satomi Nishikawa, Shin-Ichi Nishikawa, Hitoshi Niwa, Jennifer S. Park, Ethan S. Patterson, Alice Pébay, Martin F. Pera, Christopher S. Potten, Bhawana Poudel, Sean L. Preston, Nicole L. Prokopishyn, Emily K. Pugach, Jean Py. Lee, Ariane Rochat, Nadia Rosenthal, Janet Rossant, Michael Rothenberg, Michael Rubart, Alessandra Sacco, Maurilio Sampaolesi, Maria Paol. Santini, David T. Scadden, Hans Schöler, Tom Schulz, Michael J. Shamblott, William B. Slayton, Evan Y. Snyder, Frank Soldner, Gerald J. Spangrude, Lorenz Studer, M. Azim Surani, James A. Thomson, David Tosh, Tudorita Tumbar, Edward Upjohn, George Varigos, Catherine M. Verfaillie, Gordon C. Weir, J.W. Wilson, Nicholas A. Wright, Jun K. Yamashita, Holly Young, Junying Yu, Leonard I. Zon, and Thomas P. Zwaka

Published
2009

33. Contributors

Author

Michael J. Ackerman, Matthew L. Anderson, Felicita Andreotti, Brian H. Annex, Anthony Antonellis, Dmitri Artemov, James R. Bain, Peter J. Barnes, J.S. Barnholtz-Sloan, Richard C. Becker, Ivor J. Benjamin, Paul R. Billings, Simon C. Body, Mark Boguski, Stefano Bonassi, Brigitta Bondy, J. Martijn Bos, Roger E. Breitbart, Jerome Brody, Matthew P. Brown, Lars Bullinger, Shawn C. Burgess, Atul J. Butte, David J. Carey, George Carlson, Juan C. Celedón, Subhashini Chandrasekharan, Wing C. (John) Chang, Yan Chen, Antonio Chiocca, Theresa Puifun Chow, Wendy K. Chung, Robert Cook-Deegan, Dolores Corella, Susan Cottrell, Nancy J. Cox, Nigel P.S. Crawford, A. Jamie Cuticchia, Dieter Deforce, Mario C. Deng, Gayathri Devi, Theo deVos, Juergen Distler, Harmut Dohner, Ayotunde O. Dokun, Mark R. Edbrooke, Lucas B. Edelman, Dirk Elewaut, Charles J. Epstein, Ayman H. Fanous, Phillip G. Febbo, Robert J. Feezor, Yonmei Feng, Zeno Földes-Papp, Hidehiko Fujinaka, David J. Galas, Louis, P. Garrison, Glenn S. Gerhard, Geoffrey S. Ginsburg, Bjorn T. Gjertsen, Michael Glass, David B. Goldstein, Erynn S. Gordon, Tucker Gosnell, Peter Grass, Eric D. Green, Iris Grossman, Marta Gwinn, Carolina Haefliger, Susanne B. Haga, Per Hall, Joshua M. Hare, Ahmad Hariri, James R. Heath, Robert A. Hegele, Bettina Heidecker, Shona Hislop, Eric P. Hoffman, John Holton, Leroy Hood, Andrew T. Huang, Erich S. Huang, Carlos A. Hubbard, Kent Hunter, Courtney Hyland, Chunhwa Ihm, Olga Ilkayeva, Rafael Irizarry, Shushant Jain, Melissa D. Johnson, Philip W. Kantoff, Sekar Kathiresan, Hasmeena Kathuria, Kensaku Kawamoto, Filip De Keyser, Asif Khalid, Muin Khoury, Stephen F. Kingsmore, Michelle M. Kittleson, Beena T. Koshy, Ranga Krishnan, Robert S. Krouse, Vikas Kundra, Myla Lai-Goldman, Vipul Lakhani, Robert Langer, Sean E. Lawler, Inyoul Lee, Charles Lee, Arthur S. Lee, Stanely Leong, Ralf Lesche, Samuel Levy, Edison T. Liu, David F. Lobach, James B. Lorens, Aldons J. Lusis, H. Kim Lyerly, Nageswara R. Madamanchi, J. Alfredo Martinez, Vega Masignani, Kevin McGrath, John McHutchison, Frank Middleton, Herman Mielants, Michael J. Muehlbauer, Ulf Müller-Ladner, Mark A. Nelson, Monica Neri, Mihai Netea, L. Kristin Newby, Christopher B. Newgard, Maggie Ng, Paul W. Noble, Vasilis Ntziachristos, Robert L. Nussbaum, Meghan B. O'Donoghue, Kunle Odunsi, Kenneth Olden, Steve R. Ommen, Jose M. Ordovas, Roberto Patarca, Jeetendra Patel, K. Patel, Carlos N. Pato, Michele T. Pato, Tanja Pejovic, Noah C. Perin, Michael Pham, Robert M. Plenge, Achim Plum, Mihai V. Podgoreanu, Jonathan R. Pollack, Rebecca L. Pollex, Nathan D. Price, Thomas Quertermous, Francisco J. Quintana, Benjamin A. Raby, Daniel J. Rader, Sridhar Ramaswamy, Hans-Georg Rammensee, Scott D. Ramsey, Rino Rappuoli, Nader Rifai, Lisa Rimsza, Yu-Hui Rogers, Allen D. Roses, Jeffrey S. Ross, Ronenn Roubenoff, Marschall S. Runge, Maren T. Scheuner, Matthias Schuster, David A. Schwartz, Debra A. Schwinn, Chia Kee Seng, Nicholas A. Shackel, M. Frances Shannon, A. Dean Sherry, Jiaqi Shi, Kevin Shianna, Yelizaveta Shnayder, Andrew B. Singleton, T.P. Slavin, Desmond J. Smith, Rikkert L. Snoeckx, Ralph Snyderman, Avrum Spira, Colin F. Spraggs, Robert D. Stevens, Nicolas A. Stewart, Alison Stewart, F. Stewart, Robert L. Strausberg, Moshe Szyf, Weihong Tan, Robert I. Tepper, Hervé Tettelin, Giovana R. Thomas, John D. Thompson, Visith Thongboonkerd, Eric J. Topol, Jeffrey A. Towbin, Ad A. van Bodegraven, Kris Van Den Bogaert, Filip Van den Bosch, Matte Vatta, Timothy D. Veenstra, David L. Veenstra, Aleksandr E. Vendrov, Catherine M. Verfaillie, Nicole M. Walley, Ling Wang, Mike Weale, Michael E. Weinblatt, Howard L. Weiner, Scott T. Weiss, Ralph Weissleder, Samuel A. Wells, Brett R. Wenner, Ilse R. Wiechers, Georgia L. Wiesner, Janey L. Wiggs, Cisca Wijmenga, Huntington F. Willard, James M. Wilson, Nelson A. Wivel, Jay Wohlgemuth, Janet Woodcock, Christopher W. Woods, Paula W. Woon, Chana Yagil, Yoram Yagil, Tadashi Yamamoto, Gang Yao, Andrew J. Yee, Hyuntae Yoo, Y. Nancy You, Li-Rong Yu, Jean-François Zagury, Ron Zimmern, and Stephan Züchner

Published
2009

35. Multipotent Adult Progenitor Cells

Author

Catherine M. Verfaillie, Aernout Luttun, Karen Pauwelyn, Jeff Ross, Lepeng Zeng, Marta Serafini, Yuehua Jiang, and Fernando Ulloa Montoya

Published
2008

36. Transplantation of Undifferentiated, Bone Marrow‐Derived Stem Cells

Author

Karen Pauwelyn and Catherine M. Verfaillie

Subjects
Transplantation, medicine.anatomical_structure, Cell fusion, Transdifferentiation, Immunology, medicine, Bone marrow, Progenitor cell, Stem cell, Biology, Derived stem, Regenerative medicine, Neuroscience
Abstract

Stem cell research has known an enormous development, and cellular transplantation holds great promise for regenerative medicine. However, some aspects, such as the mechanisms underlying stem cell plasticity (cell fusion vs true transdifferentiation) and the functional improvement after stem cell transplantation, are highly debated. Furthermore, the great variability in methodology used by several groups, sometimes leads to confusing, contradicting results. In this chapter, we review a number of studies in this area with an eye on possible technical and other difficulties in interpretation of the obtained results.

Published
2006

37. Contributors

Author

Alaa Adassi, Iva Afrikanova, Koichi Akashi, Piero Anversa, Anthony Atala, Scott T. Avecilla, Dolores Baksh, Yann Barrandon, Stephen H. Bartelmez, Steven R. Bauer, Prosper Benhaim, Paolo Bianco, Helen M. Blau, Hans Bode, Susan Bonner-Weir, Corinne A. Boulanger, Mairi Brittan, Marianne Bronner-Fraser, Hal E. Broxmeyer, Richard K. Burt, Maeve A. Caldwell, Fernando D. Camargo, Arnold I. Caplan, Peter Carmeliet, Elena Cattaneo, Siddharthan Chandran, Howard Y. Chang, Xin Chen, Tao Cheng, Richard W. Childs, Kyunghee Choi, Dipanjan Chowdhury, Yun Shin Chung, Philippe Collas, Gay M. Crooks, Giulio Cossu, Brian R. Davis, Gabriella Cusella De Angelis, Sharon Y.R. Dent, John E. Dick, Natalie Direkze, Yuval Dor, Ryan R. Driskell, Catherine Dulac, Cynthia E. Dunbar, Hideo Ema, John F. Engelhardt, Tariq Enver, Yvonne A. Evrard, Valentina M. Factor, K. Rose Finley, Jennifer C. Fletcher, Elaine Fuchs, Margaret T. Fuller, Amiela Globerson, Victor M. Goldberg, Margaret A. Goodell, Berthold Göttgens, Elizabeth Gould, Anthony Richard Green, Joe W. Grisham, Markus Grompe, David N. Haylock, Anne L. Hazlehurst, Marc H. Hedrick, Marko E. Horb, Jerry I. Huang, H. David Humes, Haruhiko Ishii, David K. Jin, D. Leanne Jones, Jan Kajstura, Anne Kessinger, Chris Kintner, Naoko Koyano-Nakagawa, Robb Krumlauf, Thomas Küntziger, Mark A. LaBarge, Peter M. Lansdorp, Robert Lanza, Ihor Lemischka, Annarosa Leri, Joseph J. Lucas, Aernout Luttun, Michael J. Lysaght, Gerard J. Madlambayan, Gillian May, Joby L. McKenzie, Shannon McKinney-Freeman, Douglas A. Melton, Christian Mirescu, Malcolm A.S. Moore, Yo-hei Morita, Bernardo Nadal-Ginard, Hiromitsu Nakauchi, Donald Orlic, Christopher S. Potten, Sean Preston, Darwin J. Prockop, Nicole L. Prokopishyn, Shahin Rafii, Carlos Almeida Ramos, Pamela A. Raymond, Pamela Gehron Robey, Ariane Rochat, Hans-Reimer Rodewald, Nadia Rosenthal, Ferdinando Rossi, Francis W. Ruscetti, Maurilio Sampaolesi, Maria Paola Santini Laurea, David T. Scadden, Ruth Seggewiss, Ranjan Sen, J. Graham Sharp, Sergey V. Shmelkov, Mohummad Minhaj Siddiqui, Paul J. Simmons, William B. Slayton, Gilbert H. Smith, Lukas Sommer, Gerald Spangrude, Ramaprasad Srinivasan, Mark S. Szczypka, Yoshiyuki Takahashi, Rafael Tejada, Naohiro Terada, E. Donnall Thomas, James A. Thomson, Snorri S. Thorgeirsson, Marc Tjwa, David Tosh, Paul A. Trainor, David Traver, Tudorita Tumbar, Joseph P. Vacanti, Larissa Verda, Catherine M. Verfaillie, Fiona M. Watt, Gordon C. Weir, James W. Wilson, Nicholas A. Wright, Zipora Yablonka-Reuveni, Pamela C. Yelick, Jung U. Yoo, Peter W. Zandstra, Lisa Zakhary, Wen Jie Zhang, Leonard I. Zon, and Patricia A. Zuk

Published
2004

38. 'Adult' Stem Cells: Tissue Specific or Not?

Author

Catherine M. Verfaillie

Subjects
Induced stem cells, Immunology, Clinical uses of mesenchymal stem cells, Embryoid body, Stem cell, Biology, Embryonic stem cell, Adult stem cell, Cell biology, Cerebral organoid, Stem cell transplantation for articular cartilage repair
Abstract

This chapter describes the findings of apparent plasticity of adult tissue-specific stem cells. The major criticism of the claim that stem cells are more potent than previously thought is that most studies describing plasticity do not fulfill the criteria commonly used to describe stem cells: self-renewing single cells that differentiate into functional progeny and reconstitute a damaged organ in vivo. Adult stem cells are generated during development beyond the stage of gastrulation. During gastrulation, pluripotent cells become mesoderm, endoderm, and ectoderm; subsequently, issue-specific fate decisions are made. Therefore, adult stem cells have lost pluripotency and acquired tissuespecific, restricted differentiation abilities. Reports have suggested that presumed tissue-restricted stem cells may possess developmental capabilities resembling those of more immature, pluripotent cells, such as embryonic stem cells (ESC).

Published
2004

39. Multipotent Adult Progenitor Cells

Author

Catherine M. Verfaillie and Alaa Adassi

Subjects
Muscle tissue, education.field_of_study, Population, Cell, Cardiac muscle, Biology, Embryonic stem cell, Cell biology, medicine.anatomical_structure, medicine, Myocyte, Blastocyst, Progenitor cell, education
Abstract

This chapter provides updated information regarding a rare cell population named multipotent adult progenitor cells (MAPCs). MAPCs can be cultured from human, mouse, and rat bone marrow. The chapter also shows that MAPCs can be cultured from mouse brain and mouse muscle. The differentiation potential and expressed gene profile of MAPCs derived from these tissues appear to be highly similar. These studies used whole brain and muscle tissue as the initiating cell population; therefore, they contain more neural cells and muscle cells, respectively. Studies are ongoing to determine if the cultivation of MAPCs from other organs is possible and whether culture of MAPCs, like ES cells, is mouse-strain dependent. In humans, the length of MAPC telomeres is 3–5 kb longer than in neutrophils and lymphocytes, and telomere length is not different when MAPCs are derived from young or old donors. The reason MAPCs tend to differentiate to the default MSC lineage when maintained at higher densities is not known. Subsequent addition of astrocytes induced further maturation and prolonged survival of the MAPC-derived neuron-like cells, which also acquired electrophysiological characteristics consistent with neurons, namely voltage-gated sodium channels and synaptic potentials. Interestingly, the lineage that continues to be elusive is cardiac myoblasts, even though mouse MAPCs injected in the blastocyst contribute to the cardiac muscle.

Published
2004

40. Gene Therapy for Chronic Myelogenous Leukemia

Author

CATHERINE M. VERFAILLIE and ROBERT CH ZHAO

Subjects
ABL, Genetic enhancement, breakpoint cluster region, Chromosomal translocation, Biology, medicine.disease, Philadelphia chromosome, Molecular biology, Leukemia, hemic and lymphatic diseases, medicine, Cancer research, neoplasms, K562 cells, Chronic myelogenous leukemia
Abstract

This chapter discusses the gene therapy for chronic myelogenous leukemia (CML). CML is a malignancy of the hematopoietic stem cell, characterized by a reciprocal translocation between chromosomes 9 and 22 (Philadelphia chromosome [Ph]) resulting in the formation of a hybrid bcr-abl gene on chromosome 22. As CML is caused by p210 bcr-abl , suppression of the expression of p210 bcr-abl or proteins downstream in the bcr-abl signal pathway which are specifically activated by p210 bcr-abl may restore normal, nonleukemic growth of bcr-abl + cells. A large body of work has focused on targeting mRNA to eliminate target gene products. Because p210 bcr-abl is tumor specific and responsible for the development of leukemia, it is an obvious target to treat CML. Anti- bcr-abl therapy is therefore ideally targeted at the bcr-abl breakpoint and not the bcr or abl portions of the oncogene. Alternatively, therapies could be directed at molecules downstream from bcr-abl that are involved in the transformation of hematopoietic cells. This requires that activation of the downstream molecules is bcr-abl specific and is not by processes that govern normal progenitor proliferation and differentiation.

Published
2002

41. Contributors

Author

Rafat Abonour, Scott I. Abrams, Laura K. Aguilar, Estuardo Aguilar-Cordova, Steven M. Albelda, Mark R. Albertini, Gustavo Ayala, Jacques Banchereau, Christopher Baum, Christian M. Becker, Carmela Beger, Joseph R. Bertino, Patrick Blanco, Tulin Budak-Alpdogan, E. Brian Butler, Lisa H. Butterfield, Alfred E. Chang, Saswati Chatterjee, K.V. Chin, Virginia K. Clements, Mark J. Cooper, Kenneth Cornetta, James M. Croop, Samudra Dissanayake, Stephen L. Eck, James S. Economou, Laurence C. Eisenlohr, Wafik S. El-Deiry, Filip A. Farnebo, Andrew L. Feldman, Judah Folkman, Stanton L. Gerson, Mileka Gilbert, Leonard G. Gomella, David H. Gorski, William N. Hait, Mien-Chie Hung, Kevin D. Judy, Dov Kadmon, Thomas Kearney, Edsel U. Kim, David M. King, David Kirn, Omer N. Koç, Martin Krüger, Calvin J. Kuo, C. Lampert, Edmund C. Lattime, Irina V. Lebedeva, Steven K. Libutti, H. Kim Lyerly, Michael J. Mastrangelo, Helena J. Mauceri, A.M. McCall, Kevin T. McDonagh, R. Scott McIvor, Raymond D. Meng, Brian Miles, Frederick L. Moolten, Michael A. Morse, Paula J. Mroz, James J. Mulé, Smita K. Nair, Owen A. O'Connor, Wolfram Ostertag, Suzanne Ostrand-Rosenberg, A. Karolina Palucka, Beth A. Pulaski, Ling Qi, Alexander L. Rakhmilevich, Jane S. Reese, Michael Reiss, Antoni Ribas, Isabelle Rivière, Justin C. Roth, Michel Sadelain, Ruping Shao, C.A. Stein, Daniel H. Sterman, Carol Stocking, Bin S. Teh, Timothy C. Thompson, Deborah Toppmeyer, Catherine M. Verfaillie, Maria T. Vlachaki, Dorothee von Laer, Ralph R. Weichselbaum, L.M. Weiner, Thomas Wheeler, Lee G. Wilke, K.K. Wong, Flossie Wong-Staal, Duen-Hwa Yan, Steven P. Zielske, and Robert CH Zhao

Published
2002

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