Papers by Donald G Phinney
except for brief excerpts in connection with reviews or scholarly analysis. Use in connection wit... more except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.
Cancer Research, May 1, 2009
Osteosarcoma is the most common primary bone tumor in adolescents associated with skeletal develo... more Osteosarcoma is the most common primary bone tumor in adolescents associated with skeletal development. The molecular pathogenesis of osteosarcoma is unknown. The whole-genome transcriptional profiles of osteosarcomas, including two primary biopsy specimens, two cell lines, two patient specimen-derived xenografts, and normal osteoblasts and mesenchymal stem cells (MSC) were quantitatively measured using serial analysis of gene expression (SAGE). A two-step statistical enrichment was performed, which selects those common genes altered in each of the osteosarcomas as compared with each of the normal counterparts independently. Sixty (92%) of 65 total genes that were down-regulated in osteosarcoma could be classified into four categories: 1) seven genes in the insulin-like growth factor (IGF) signaling axis, including three of the IGF binding proteins (IGFBP) and three of the IGFBP related proteins (IGFBPrP); 2) eight genes in the transforming growth factor-beta (TGF-\#946;)/bone morphogenetic proteins (BMP) signaling cascade; 3) thirty-nine genes encoding cytoskeleton and extracellular matrix proteins that are regulated by TGF-\#946;/BMPs; and 4) six genes involved in cell cycle regulation, including tumor suppressors TP63 and p21. Based on these transcriptional profiles, a coordinated theme of clustered gene deregulation in osteosarcoma has emerged. Cell proliferation driven by the IGF axes during bone growth is unrestrained due to down-regulation of IGFBPs and cell cycle regulators. Tumor cells may be maintained in an undifferentiated state secondary to impaired TGF-\#946;/>/BMP signaling. This well-preserved pattern suggests that the alterations in the signaling axes of IGF-1 and TGF-\#946;, in concert with cell cycle regulators, may be the pathogenic basis of osteosarcoma. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3119.
Expert Opinion on Drug Discovery, Aug 17, 2022
PubMed, Aug 1, 1994
We have identified four DNAase I-hypersensitive regions (DHRs) at the junB locus. DHR1 is located... more We have identified four DNAase I-hypersensitive regions (DHRs) at the junB locus. DHR1 is located between sequences -100 and +250, DHR2 is centered at -1000, DHR3 at -1650, and DHR4 at +2040 relative to the junB transcriptional start site. Sequence analysis of these DHRs revealed two serum response elements at -1452 and +2091, two cyclic AMP response elements at +2071 and +2116, and a 12-O-tetradecanoylphorbol-13-acetate (TPA) response element at -949. To study the contribution made by these cis-elements to junB transcriptional regulation, we stably transfected a recombinant mouse junB gene (JBSV4) containing the intact junB coding sequences, 6.3 kb of 5'-flanking DNA, and 2.0 kb of 3'-flanking DNA into Rat1A cells. The pattern of DHRs identified at the mouse junB locus was re-established at the JBSV4 locus. By directly comparing JBSV4 and rat junB mRNA levels, we found that these genes were induced to equivalent levels by serum, TPA, cyclic AMP, platelet-derived growth factor, epidermal growth factor, and basic fibroblastic growth factor. These results established that JBSV4 resides in a physical environment within chromatin that closely mimics that of the junB locus, and contains the necessary sequence information to recapitulate the transcriptional regulation of junB. By analysing a series of recombinant mouse junB genes containing deletion mutations in 5'-flanking and 3'-flanking sequences, we provide a quantitative assessment of the contribution these sequences make to junB induction by different regulatory agents.
Chemischer Informationsdienst, Jul 16, 1985
Synthesis of Unsymmetrical Ketones via Simple C-H Activation of Aldehydes and Concomitant Hydroac... more Synthesis of Unsymmetrical Ketones via Simple C-H Activation of Aldehydes and Concomitant Hydroacylation of Vinyl Sulfonates.-Direct reaction of aldehydes (I), (V) with vinyl sulfonates (II) and (VI) is smoothly achieved by activation of the aldehyde carbonyl group under aerobic conditions or in the presence of hydrogen peroxide. The reaction proceeds via a radical mechanism.-(FITZMAURICE, R. J.;
Journal of Biological Chemistry, May 1, 1995
Humana Press eBooks, 2011
Cytotherapy, Sep 1, 2001
Friedenstein and co-workers were the first to recognize that BM contains an adherent, fibroblast-... more Friedenstein and co-workers were the first to recognize that BM contains an adherent, fibroblast-like population, commonly referred to as marrow stromal cells (MSCs), that, under the appropriate conditions, in vivo can generate the rudiments of normal bone, including cartilage, bone, adipose, and myelosupportive stroma [1,2]. Subsequent isolation of clonegenic MSC populations that exhibit bi-, tri-, and quadri-potential differentiation in vitro [3], or are capable of producing in vivo a miniature ossicle that supports hematopoiesis [4,5] confirmed the multi-potential nature of the cells. These and other studies have culminated in the construction of a mesengenic lineage that, by convention, postulates the existence of a mesenchymal stem cell [6], and several studies have equated this stem cell with MSCs [7, 8]. Unfortunately, demonstrating the ability of MSCs to serially reconstitute multiple mesodermal tissues of an animal (a measure of self-renewal) has been prohibited by the slow turnover rate of connective tissues. This shortcoming has generated controversy about whether it is appropriate to categorize MSCs as stem cells. The issue is further complicated by the fact that no single set of criteria encompasses all of the properties displayed by different stem cell populations, making the definition of a stem cell ambiguous. Moreover, recent studies reporting the conversion of 'brain into blood' [9] and 'blood into brain' [10, 11], exemplify the shortcomings of our current knowledge regarding the plasticity of somatic cells. The ability to differentiate into astrocytes following transplantation into the developing central nervous system [12] indicates that MSCs are equally plastic in their developmental potential as other bona fide stem-cell
Cytotherapy, 2020
Over the past year, Cytotherapy has undergone significant changes in design and content including... more Over the past year, Cytotherapy has undergone significant changes in design and content including a new cover design and artwork, expanded aims and scope, new Associate Editors, new features, and an expanded Editorial Board. Last year the journal also received its highest impact factor (4.297) in its history. Therefore, I strongly believe Cytotherapy is a premiere journal to publish research related to the fields of cell and gene therapy. The International Society for Cell & Gene Therapy (ISCT) will be holding the ISCT 2020 Paris Virtual Meeting on May 28 th and 29 th. This meeting has attracted a record number (>500) of abstract submissions, which reflects the enormous growth in the fields of cell and gene therapy over the past decade. As Senior Editor for Cytotherapy, the official ISCT journal, I am pleased to invite all abstract presenters and speakers participating in ISCT 2020 Paris Virtual to submit their research results to Cytotherapy for publication. Manuscript submissions will be accepted on a continuous basis and there is no deadline for submission. Topics of interest include
Biochimica et biophysica acta (N), Jul 1, 1988
Transcription of a light-inducible gene in the prokaryote Arthrobacter sp. is induced in the dark... more Transcription of a light-inducible gene in the prokaryote Arthrobacter sp. is induced in the dark when cells are incubated with chelating agents or in medium at pH 5. However, repletion of metal ions such as Ca 2÷, Mn 2+ or Zn 2+ or an increase in pH is required for accumulation of the gene product, an M r 21000 polypeptide. But such changes in condition restore repression of the gene, and the decay in the rate of synthesis of the polypeptide follows the same time-course as when photodynamically induced cells are transferred to the dark. These results are consistent with regulation of expression of this gene at transcriptional and posttranscriptional steps by mechanisms that involve metal-protein complexes. Exposure of Arthrobacter sp. cells to near-ultraviolet light strongly stimulates expression of a gene that encodes an M r 21 000, cell-surface polypeptide, designated P21 [1]. The endogenous photoreceptor of near-ultraviolet light can be substituted in visible light by photodynamic dyes [1-3]. Since general oxidants are not effective [3], the sensitivity of this gene to mild photodynamic conditions suggests that a selective photooxidative reaction induces its expression. The data described in this report show that the gene can also be induced in the dark by treating cells with chelating agents or medium at pH 5. These findings suggest that expression of this gene is controlled by metal-protein complexes.
Cytotherapy, Dec 1, 2021
The Cellular Therapy Coding and Labeling Advisory Group of the International Council for Commonal... more The Cellular Therapy Coding and Labeling Advisory Group of the International Council for Commonality in Blood Banking Automation and the International Society for Cell & Gene Therapy mesenchymal stromal cell (MSC) committee are providing specific recommendations on abbreviating tissue sources of culture-adapted MSCs. These recommendations include using abbreviations based on the ISBT 128 terminology model that specifies standard class names to distinguish cell types and tissue sources for culture-adapted MSCs. Thus, MSCs from bone marrow are MSC(M), MSCs from cord blood are MSC(CB), MSCs from adipose tissue are MSC(AT) and MSCs from Wharton's jelly are MSC(WJ). Additional recommendations include using these abbreviations through the full spectrum of pre-clinical, translational and clinical research for the development of culture-adapted MSC products. This does not apply to basic research focused on investigating the developmental origins, identity or functionalities of endogenous progenitor cells in different tissues. These recommendations will serve to harmonize nomenclature in describing research and development surrounding culture-adapted MSCs, many of which are destined for clinical and/or commercial translation. These recommendations will also serve to align research and development efforts on culture-adapted MSCs with other cell therapy products.
Humana Press eBooks, 2008
Journal of Cellular Biochemistry, Jul 29, 2003
Mesenchymal stem cells (MSCs) are typically enriched from bone marrow via isolation of the plasti... more Mesenchymal stem cells (MSCs) are typically enriched from bone marrow via isolation of the plastic adherent, fibroblastoid cell fraction. However, plastic adherent cultures elaborated from murine bone marrow are an admixture of fibroblastoid and hematopoietic cell types. Here we report a reliable method based on immunodepletion to fractionate fibroblastoid cells from hematopoietic cells within plastic adherent murine marrow cultures. The immunodepleted cells expressed the antigens Sca-1, CD29, CD44, CD81, CD106, and the stem cell marker nucleostemin (NST) but not CD11b, CD31, CD34, CD45, CD48, CD90, CD117, CD135, or the transcription factor Oct-4. They were also capable of differentiating into adipocytes, chondrocytes, and osteoblasts in vitro as well as osteoblasts/osteocytes in vivo. Therefore, immunodepletion yields a cell population devoid of hematopoietic and endothelial cells that is phenotypically and functionally equivalent to MSCs. The immunodepleted cells exhibited a population doubling time of approximately 5-7 days in culture. Poor growth was due to the dramatic down regulation of many genes involved in cell proliferation and cell cycle progression as a result of immunodepletion. Exposure of immunodepleted cells to fibroblast growth factor 2 (FGF2) but not insulin-like growth factor (IGF), murine stem cell factor, or leukemia inhibitory factor (LIF) significantly increased their growth rate. Moreover, 82% of the transcripts down regulated by immunodepletion remain unaltered in the presence of FGF2. Exposure to the later also reversibly inhibited the ability of the immunodepleted cells to differentiate into adipocytes, chondrocytes, and osteoblasts in vitro. Therefore, FGF2 appears to function as a mitogen and self-maintenance factor for murine MSCs enriched from bone marrow by negative selection.
Table of Contents: Preface. Darwin J. Prockop, Donald G. Phinney, Bruce A. Bunnell Part I: Isolat... more Table of Contents: Preface. Darwin J. Prockop, Donald G. Phinney, Bruce A. Bunnell Part I: Isolation of human multipotential stromal cells from bone marrow and adipose tissue. Chapter 1. Isolation and culture of bone marrow-derived human multipotent stromal cells (hMSCs). Margaret Wolfe, Radhika Pochampally, William Swaney and Roxanne Reger Chapter 2. Mesenchymal stem cells from adult bone marrow. Mark F. Pittenger Chapter 3. A method to isolate and purify human bone marrow stromal stem cells. Stan Gronthos and Andrew C. W. Zannettino Chapter 4. Adipose-derived stem cells. John K. Fraser, Min Zhu, Isabella Wulur and Zeni Alfonso Chapter 5. Isolation of human adipose-derived stem cells from biopsies and liposuction specimens. Severine G Dubois, Z. Elizabeth Floyd, Sanjin Zvonic, Gail Kilroy, Xiying Wu, Stacy Carling, Yuan Di C. Halvorsen, Eric Ravussin and Jeffrey M Gimble Part II: Manipulation of human multipotential stromal cells. Chapter 6. Colony forming unit assays for MSCs. Radhika Pochampally Chapter 7. Differentiation and characterization of human MSCs. Roxanne L. Reger, H. Alan Tucker, and Margaret R. Wolfe Chapter 8. Freezing harvested hMSCs and recovery of hMSCs from frozen vials for subsequent expansion, analysis and experimentation. Roxanne L. Reger and Margaret R. Wolfe Chapter 9. Gene expression analysis at the single cell level using the human bone marrow stromal cell as a model: sample preparation methods. Beerelli Seshi Chapter 10. Assays of MSCs with microarrays. Joni Ylostalo, Radhika Pochampally and Darwin J. Prockop Chapter 11. Gene delivery to mesenchymal stem cells. Reza Izadpanah andBruce A. Bunnell Part III: Isolation and characterization of murine multipotential stromal cells from bone marrow. Chapter 12. Isolation of mesenchymal stem cells from murine bone marrow by Immunodepletion. Donald G. Phinney
Aging Cell, Mar 16, 2021
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Papers by Donald G Phinney