Indiana University

Harvard College

The General Hospital Corporation

Jonathan Hoggatt

Louis M Pelus

Pratibha Singh

David T Scadden

Borja Saez

Francesca Ferraro

The receptor EPis identified as the PGEreceptor that is most responsible enhancing the homing and engraftment of hematopoietic stem and progenitor cells. Treatment of graft sources and graft recipients with compounds that preferentially target the EPreceptor provide effective methods of increasing engraftment success while minimizing adverse side effects that may be associated with therapies that include the use of less selective molecules such as PGEand dmPGE. One effective molecule used in such therapies is 5-[(1E,3R)-4,4-difluoro-3-hydroxy-4-phenyl-1-buten-1-yl]-1-[6-(2H-tetrazol-5R-yl)hexyl]-2-pyrrolidinone or a pharmaceutically acceptable salt thereof (L-902, 688).

Methods to enhance delivery and engraftment of stem cells including the identification of specific prostaglandin E2 receptors

This disclosure is directed to the methods of enhancing hematopoietic stem cells (HSPC) and progenitor cell (HSPC) engraftment procedure. Treatment in vivo of a HSPC donor with compounds that reduce PGEbiosynthesis or PGEreceptor antagonists alone, or in combination with other hematopoietic mobilization agents such as AMD3100 and G-CSF, increases the circulation of available HSPCs. Compounds that reduce the cellular synthesis of PGEinclude non-steroidal anti-inflammatory compounds such as indomethacin. Treatment ex vivo of HSPC with an effective amount of PGEor at least one of its derivatives such as 16,16-dimethyl prostaglandin E(dmPGE), promotes HSPC engraftment. Similar methods may also be used to increase viral-mediated gene transduction efficacy into HSPC.

Materials and methods to enhance hematopoietic stem cells engraftment procedures

The present invention relates to methods and compositions for mobilizing hematopoietic stem cells and/or progenitor cells, and related methods of conditioning for engraftment of transplanted hematopoietic stem cells and/or progenitor cells, and methods of treating diseases requiring hematopoietic stem cell and/or progenitor cell transplantation.

Methods and compositions for mobilizing stem cells

Growing community of inventors

Somerville, MA, United States of America

Jonathan Hoggatt