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Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell.
Hoggatt, Jonathan; Singh, Pratibha; Tate, Tiffany A; Chou, Bin-Kuan; Datari, Shruti R; Fukuda, Seiji; Liu, Liqiong; Kharchenko, Peter V; Schajnovitz, Amir; Baryawno, Ninib; Mercier, Francois E; Boyer, Joseph; Gardner, Jason; Morrow, Dwight M; Scadden, David T; Pelus, Louis M.
Afiliação
  • Hoggatt J; Harvard Medical School, Cancer Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02129, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic addr
  • Singh P; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Tate TA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Chou BK; Harvard Medical School, Cancer Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02129, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
  • Datari SR; Harvard Medical School, Cancer Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02129, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
  • Fukuda S; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Liu L; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Kharchenko PV; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Schajnovitz A; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Baryawno N; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Mercier FE; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Boyer J; Department of Statistical Sciences, GlaxoSmithKline, Collegeville, PA 19426, USA; GlaxoSmithKline, Collegeville, PA 19426, USA.
  • Gardner J; GlaxoSmithKline, Collegeville, PA 19426, USA.
  • Morrow DM; GlaxoSmithKline, Collegeville, PA 19426, USA.
  • Scadden DT; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: david_scadden@harvard.edu.
  • Pelus LM; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: lpelus@iupui.edu.
Cell ; 172(1-2): 191-204.e10, 2018 01 11.
Article em En | MEDLINE | ID: mdl-29224778
ABSTRACT
Hematopoietic stem cell transplantation is a potential curative therapy for malignant and nonmalignant diseases. Improving the efficiency of stem cell collection and the quality of the cells acquired can broaden the donor pool and improve patient outcomes. We developed a rapid stem cell mobilization regimen utilizing a unique CXCR2 agonist, GROß, and the CXCR4 antagonist AMD3100. A single injection of both agents resulted in stem cell mobilization peaking within 15 min that was equivalent in magnitude to a standard multi-day regimen of granulocyte colony-stimulating factor (G-CSF). Mechanistic studies determined that rapid mobilization results from synergistic signaling on neutrophils, resulting in enhanced MMP-9 release, and unexpectedly revealed genetic polymorphisms in MMP-9 that alter activity. This mobilization regimen results in preferential trafficking of stem cells that demonstrate a higher engraftment efficiency than those mobilized by G-CSF. Our studies suggest a potential new strategy for the rapid collection of an improved hematopoietic graft.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Transplante de Células-Tronco Hematopoéticas / Mobilização de Células-Tronco Hematopoéticas Limite: Adult / Animals / Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Transplante de Células-Tronco Hematopoéticas / Mobilização de Células-Tronco Hematopoéticas Limite: Adult / Animals / Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article