Materials and methods to enhance hematopoietic stem cells engraftment procedures
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 PGE 2 biosynthesis or PGE 2 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 PGE 2 include non-steroidal anti-inflammatory compounds such as indomethacin. Treatment ex vivo of HSPC with an effective amount of PGE 2 or at least one of its derivatives such as 16,16-dimethyl prostaglandin E 2 (dmPGE 2 ), promotes HSPC engraftment. Similar methods may also be used to increase viral-mediated gene transduction efficacy into HSPC.
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 E 2 or a derivative thereof; and
transfecting the human hematopoietic stem or progenitor cell treated with the prostaglandin E 2 or a derivative thereof with the viral vector.
2. The method according to claim 1 , wherein the prostaglandin E 2 derivative is a dimethyl-derivative of prostaglandin E 2 .
3. The method according to claim 1 , wherein the prostaglandin E 2 derivative is 16,16-dimethyl prostaglandin E 2 .
4. The method according to claim 1 , wherein said method further comprises the step of engrafting the human hematopoietic stem or progenitor cell into a patient.