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  1. AU="Rahman, Nafees"
  2. AU="Gotsi, Anna"
  3. AU="Pathak, Saurabh Kumar"
  4. AU="Khanji, Mohammed Yunus"
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  15. AU="Katerina Galai"
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  1. Article ; Online: A Multi-Lineage Screen Reveals mTORC1 Inhibition Enhances Human Pluripotent Stem Cell Mesendoderm and Blood Progenitor Production.

    Nazareth, Emanuel Joseph Paul / Rahman, Nafees / Yin, Ting / Zandstra, Peter William

    Stem cell reports

    2016  Volume 6, Issue 5, Page(s) 679–691

    Abstract: Human pluripotent stem cells (hPSCs) exist in heterogeneous micro-environments with multiple subpopulations, convoluting fate-regulation analysis. We patterned hPSCs into engineered micro-environments and screened responses to 400 small-molecule kinase ... ...

    Abstract Human pluripotent stem cells (hPSCs) exist in heterogeneous micro-environments with multiple subpopulations, convoluting fate-regulation analysis. We patterned hPSCs into engineered micro-environments and screened responses to 400 small-molecule kinase inhibitors, measuring yield and purity outputs of undifferentiated, neuroectoderm, mesendoderm, and extra-embryonic populations. Enrichment analysis revealed mammalian target of rapamycin (mTOR) inhibition as a strong inducer of mesendoderm. Dose responses of mTOR inhibitors such as rapamycin synergized with Bone Morphogenetic protein 4 (BMP4) and activin A to enhance the yield and purity of BRACHYURY-expressing cells. Mechanistically, small interfering RNA knockdown of RAPTOR, a component of mTOR complex 1, phenocopied the mesendoderm-enhancing effects of rapamycin. Functional analysis during mesoderm and endoderm differentiation revealed that mTOR inhibition increased the output of hemogenic endothelial cells 3-fold, with a concomitant enhancement of blood colony-forming cells. These data demonstrate the power of our multi-lineage screening approach and identify mTOR signaling as a node in hPSC differentiation to mesendoderm and its derivatives.
    Language English
    Publishing date 2016-05-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2720528-9
    ISSN 2213-6711 ; 2213-6711
    ISSN (online) 2213-6711
    ISSN 2213-6711
    DOI 10.1016/j.stemcr.2016.04.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Engineering the haemogenic niche mitigates endogenous inhibitory signals and controls pluripotent stem cell-derived blood emergence.

    Rahman, Nafees / Brauer, Patrick M / Ho, Lilian / Usenko, Tatiana / Tewary, Mukul / Zúñiga-Pflücker, Juan Carlos / Zandstra, Peter W

    Nature communications

    2017  Volume 8, Page(s) 15380

    Abstract: Efforts to recapitulate haematopoiesis, a process guided by spatial and temporal inductive signals, to generate haematopoietic progenitors from human pluripotent stem cells (hPSCs) have focused primarily on exogenous signalling pathway activation or ... ...

    Abstract Efforts to recapitulate haematopoiesis, a process guided by spatial and temporal inductive signals, to generate haematopoietic progenitors from human pluripotent stem cells (hPSCs) have focused primarily on exogenous signalling pathway activation or inhibition. Here we show haemogenic niches can be engineered using microfabrication strategies by micropatterning hPSC-derived haemogenic endothelial (HE) cells into spatially-organized, size-controlled colonies. CD34+VECAD+ HE cells were generated with multi-lineage potential in serum-free conditions and cultured as size-specific haemogenic niches that displayed enhanced blood cell induction over non-micropatterned cultures. Intra-colony analysis revealed radial organization of CD34 and VECAD expression levels, with CD45+ blood cells emerging primarily from the colony centroid area. We identify the induced interferon gamma protein (IP-10)/p-38 MAPK signalling pathway as the mechanism for haematopoietic inhibition in our culture system. Our results highlight the role of spatial organization in hPSC-derived blood generation, and provide a quantitative platform for interrogating molecular pathways that regulate human haematopoiesis.
    MeSH term(s) Animals ; Antigens, CD/metabolism ; Antigens, CD34/metabolism ; Cadherins/metabolism ; Cell Differentiation ; Cell Engineering/methods ; Cell Line ; Cell Lineage ; Chemokine CXCL10/metabolism ; Culture Media, Serum-Free ; Female ; Hemangioblasts/cytology ; Hemangioblasts/metabolism ; Hemangioblasts/transplantation ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Heterografts ; Humans ; Leukocyte Common Antigens/metabolism ; Mice ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Pluripotent Stem Cells/transplantation ; Signal Transduction ; Stem Cell Niche
    Chemical Substances Antigens, CD ; Antigens, CD34 ; CXCL10 protein, human ; Cadherins ; Chemokine CXCL10 ; Culture Media, Serum-Free ; cadherin 5 ; Leukocyte Common Antigens (EC 3.1.3.48) ; PTPRC protein, human (EC 3.1.3.48)
    Language English
    Publishing date 2017-05-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms15380
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: High-throughput micropatterning platform reveals Nodal-dependent bisection of peri-gastrulation-associated versus preneurulation-associated fate patterning.

    Tewary, Mukul / Dziedzicka, Dominika / Ostblom, Joel / Prochazka, Laura / Shakiba, Nika / Heydari, Tiam / Aguilar-Hidalgo, Daniel / Woodford, Curtis / Piccinini, Elia / Becerra-Alonso, David / Vickers, Alice / Louis, Blaise / Rahman, Nafees / Danovi, Davide / Geens, Mieke / Watt, Fiona M / Zandstra, Peter W

    PLoS biology

    2019  Volume 17, Issue 10, Page(s) e3000081

    Abstract: In vitro models of postimplantation human development are valuable to the fields of regenerative medicine and developmental biology. Here, we report characterization of a robust in vitro platform that enabled high-content screening of multiple human ... ...

    Abstract In vitro models of postimplantation human development are valuable to the fields of regenerative medicine and developmental biology. Here, we report characterization of a robust in vitro platform that enabled high-content screening of multiple human pluripotent stem cell (hPSC) lines for their ability to undergo peri-gastrulation-like fate patterning upon bone morphogenetic protein 4 (BMP4) treatment of geometrically confined colonies and observed significant heterogeneity in their differentiation propensities along a gastrulation associable and neuralization associable axis. This cell line-associated heterogeneity was found to be attributable to endogenous Nodal expression, with up-regulation of Nodal correlated with expression of a gastrulation-associated gene profile, and Nodal down-regulation correlated with a preneurulation-associated gene profile expression. We harness this knowledge to establish a platform of preneurulation-like fate patterning in geometrically confined hPSC colonies in which fates arise because of a BMPs signalling gradient conveying positional information. Our work identifies a Nodal signalling-dependent switch in peri-gastrulation versus preneurulation-associated fate patterning in hPSC cells, provides a technology to robustly assay hPSC differentiation outcomes, and suggests conserved mechanisms of organized fate specification in differentiating epiblast and ectodermal tissues.
    MeSH term(s) Biomechanical Phenomena ; Body Patterning/genetics ; Bone Morphogenetic Protein 4/genetics ; Bone Morphogenetic Protein 4/metabolism ; Bone Morphogenetic Protein 4/pharmacology ; Cell Culture Techniques ; Cell Differentiation/drug effects ; Cell Line ; Cell Lineage/drug effects ; Cell Lineage/genetics ; Gastrulation/drug effects ; Gastrulation/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genetic Heterogeneity ; High-Throughput Screening Assays ; Humans ; Models, Biological ; Neurogenesis/drug effects ; Neurogenesis/genetics ; Nodal Protein/genetics ; Nodal Protein/metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/drug effects ; Pluripotent Stem Cells/metabolism ; Signal Transduction ; Surface Properties
    Chemical Substances BMP4 protein, human ; Bone Morphogenetic Protein 4 ; NODAL protein, human ; Nodal Protein
    Language English
    Publishing date 2019-10-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3000081
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6193: Show issues Location:
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  4. Article ; Online: The use of vascular endothelial growth factor functionalized agarose to guide pluripotent stem cell aggregates toward blood progenitor cells.

    Rahman, Nafees / Purpura, Kelly A / Wylie, Ryan G / Zandstra, Peter W / Shoichet, Molly S

    Biomaterials

    2010  Volume 31, Issue 32, Page(s) 8262–8270

    Abstract: The developmental potential of pluripotent stem cells is influenced by their local cellular microenvironment. To better understand the role of vascular endothelial growth factor (VEGFA) in the embryonic cellular microenvironment, we synthesized an ... ...

    Abstract The developmental potential of pluripotent stem cells is influenced by their local cellular microenvironment. To better understand the role of vascular endothelial growth factor (VEGFA) in the embryonic cellular microenvironment, we synthesized an artificial stem cell niche wherein VEGFA was immobilized in an agarose hydrogel. Agarose was first modified with coumarin-protected thiols. Upon exposure to ultra-violet excitation, the coumarin groups were cleaved leaving reactive thiols to couple with maleimide-activated VEGFA. Mouse embryonic stem cells (ESC) aggregates were encapsulated in VEGFA immobilized agarose and cultured for 7 days as free-floating aggregates under serum-free conditions. Encapsulated aggregates were assessed for their capacity to give rise to blood progenitor cells. In the presence of bone morphogenetic protein-4 (BMP-4), cells exposed to immobilized VEGFA upregulated mesodermal markers, brachyury and VEGF receptor 2 (T+VEGFR2+) by day 4, and expressed CD34 and CD41 (CD34+CD41+) on day 7. It was found that immobilized VEGFA treatment was more efficient at inducing blood progenitors (including colony forming cells) on a per molecule basis than soluble VEGFA. This work demonstrates the use of functionalized hydrogels to guide encapsulated ESCs toward blood progenitor cells and introduces a tool capable of recapitulating aspects of the embryonic microenvironment.
    MeSH term(s) Animals ; Blood Cells/cytology ; Blood Cells/metabolism ; Cell Differentiation ; Cell Line ; Chymotrypsinogen/chemistry ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Immobilized Proteins/chemistry ; Immobilized Proteins/metabolism ; Mice ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Sepharose/chemistry ; Sepharose/metabolism ; Sulfhydryl Compounds/chemistry ; Vascular Endothelial Growth Factor A/chemistry ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Immobilized Proteins ; Sulfhydryl Compounds ; Vascular Endothelial Growth Factor A ; Sepharose (9012-36-6) ; Chymotrypsinogen (9035-75-0)
    Language English
    Publishing date 2010-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2010.07.040
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    In stock of ZB MED Cologne/Königswinter

    Zs.B 2371: Show issues Location:
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  5. Article: The relationship between hand strength and the forces used to access containers by well elderly persons.

    Rahman, Nafees / Thomas, Julie Jepsen / Rice, Martin S

    The American journal of occupational therapy : official publication of the American Occupational Therapy Association

    2002  Volume 56, Issue 1, Page(s) 78–85

    Abstract: Objective: This study extended previous work of Rice, Leonard, and Carter [AJOT, 52(8), 621-626] and examined the relationship between grip and pinch strengths and the forces produced while accessing common household containers in healthy, elderly ... ...

    Abstract Objective: This study extended previous work of Rice, Leonard, and Carter [AJOT, 52(8), 621-626] and examined the relationship between grip and pinch strengths and the forces produced while accessing common household containers in healthy, elderly persons.
    Method: Forty-two women and 9 men 60 years of age and older were assigned randomly to one of four order groups in a counterbalanced, repeated-measures design. Grip strength was measured via a dynamometer and pinch strength via a pinch meter. The forces required to access six common household containers were measured with force sensing resistors applied to each container. Data analysis included Pearson product-moment correlations between the dependent variables of grip and pinch strength and force produced on the containers. Analyses of variance were used to determine differences by gender on the dependent measures and order of presentation of containers.
    Results: A fair relationship (r = .31 to .44) was found between grip and pinch strength and the ability to open three containers. Little or no relationship was found between grip and pinch strength and the ability to open the remaining three containers (r = -.03 to .25). Significant gender differences existed on overall strength and the force used to access two of the six containers. No order effects were found.
    Conclusions: Strong relationships did not exist between the grip and pinch strength and the amount of force the elderly participants used to open the containers, which is similar to what Rice et al. found for younger persons. The participants appeared to use a greater proportion of their available strength when accessing the containers than did their younger counterparts previously studied. Further research is needed to determine at what level of weakness one would expect to see performance deficits in common daily occupations.
    MeSH term(s) Activities of Daily Living ; Age Factors ; Aged ; Aging/physiology ; Analysis of Variance ; Female ; Hand/physiology ; Hand Strength/physiology ; Humans ; Male ; Middle Aged ; Occupational Therapy/methods ; Pressure ; Product Packaging/methods ; Prospective Studies ; Reference Values ; Sex Factors ; Stress, Mechanical
    Language English
    Publishing date 2002-02-07
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Randomized Controlled Trial
    ZDB-ID 219403-x
    ISSN 1943-7676 ; 0272-9490 ; 0161-326X
    ISSN (online) 1943-7676
    ISSN 0272-9490 ; 0161-326X
    DOI 10.5014/ajot.56.1.78
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 319: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  6. Article: Report of the International Stem Cell Banking Initiative Workshop Activity: Current Hurdles and Progress in Seed-Stock Banking of Human Pluripotent Stem Cells.

    Kim, Jung-Hyun / Kurtz, Andreas / Yuan, Bao-Zhu / Zeng, Fanyi / Lomax, Geoff / Loring, Jeanne F / Crook, Jeremy / Ju, Ji Hyeon / Clarke, Laura / Inamdar, Maneesha S / Pera, Martin / Firpo, Meri T / Sheldon, Michael / Rahman, Nafees / O'Shea, Orla / Pranke, Patricia / Zhou, Qi / Isasi, Rosario / Rungsiwiwut, Ruttachuk /
    Kawamata, Shin / Oh, Steve / Ludwig, Tenneille / Masui, Tohru / Novak, Thomas J / Takahashi, Tsuneo / Fujibuchi, Wataru / Koo, Soo Kyung / Stacey, Glyn N

    Stem cells translational medicine

    2017  Volume 6, Issue 11, Page(s) 1956–1962

    Abstract: This article summarizes the recent activity of the International Stem Cell Banking Initiative (ISCBI) held at the California Institute for Regenerative Medicine (CIRM) in California (June 26, 2016) and the Korean National Institutes for Health in Korea ( ... ...

    Abstract This article summarizes the recent activity of the International Stem Cell Banking Initiative (ISCBI) held at the California Institute for Regenerative Medicine (CIRM) in California (June 26, 2016) and the Korean National Institutes for Health in Korea (October 19-20, 2016). Through the workshops, ISCBI is endeavoring to support a new paradigm for human medicine using pluripotent stem cells (hPSC) for cell therapies. Priority considerations for ISCBI include ensuring the safety and efficacy of a final cell therapy product and quality assured source materials, such as stem cells and primary donor cells. To these ends, ISCBI aims to promote global harmonization on quality and safety control of stem cells for research and the development of starting materials for cell therapies, with regular workshops involving hPSC banking centers, biologists, and regulatory bodies. Here, we provide a brief overview of two such recent activities, with summaries of key issues raised. Stem Cells Translational Medicine 2017;6:1956-1962.
    MeSH term(s) Biological Specimen Banks/organization & administration ; Biological Specimen Banks/standards ; Congresses as Topic ; Human Embryonic Stem Cells/cytology ; Humans ; International Cooperation ; Stem Cell Research
    Language English
    Publishing date 2017-10-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2642270-0
    ISSN 2157-6580 ; 2157-6564
    ISSN (online) 2157-6580
    ISSN 2157-6564
    DOI 10.1002/sctm.17-0144
    Database MEDical Literature Analysis and Retrieval System OnLINE

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