Materials and methods to enhance hematopoietic stem cells engraftment procedures

摘要

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 PGE2 biosynthesis or PGE2 receptor 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 PGE2 include non-steroidal anti-inflammatory compounds such as indomethacin. Treatment ex vivo of HSPC with an effective amount of PGE2 or at least one of its derivatives such as 16,16-dimethyl prostaglandin E2 (dmPGE2), promotes HSPC engraftment. Similar methods may also be used to increase viral-mediated gene transduction efficacy into HSPC.

主权项

1. A method of enhancing viral transduction efficacy in a human hematopoietic stem or progenitor cell, comprising the steps of:
providing a viral vector that contains at least one gene of interest for transduction; supplying at least one human hematopoietic stem or progenitor cell that has been treated ex vivo with an effective amount of prostaglandin E2 or a derivative thereof; and transfecting the human hematopoietic stem or progenitor cell treated with the prostaglandin E2 or a derivative thereof with the viral vector.