Retrovirus receptor mRNA expression correlates with gene transfer efficiency in pluripotent hematopoietic stem cells.

Hematopoietic stem cells (HSC) from bone marrow, peripheral blood and cord blood are important in clinical transplantation. However, their use in gene therapy protocols is still limited by a low level of transduction efficiency. In addition to the cell cycling block to retrovirus transduction, we recently demonstrated that the low level of retrovirus receptor mRNA in mouse HSC correlated with the low level of amphotropic retrovirus transduction in these cells. Similarly, we found low levels of mRNA encoding the amphotropic retrovirus receptor in human bone marrow Lin CD34+ CD38- HSC. In an effort to identify an alternative population of human HSC that might be more efficiently transduced, we assayed HSC populations from cord blood for mRNA encoding the amphotropic retrovirus receptor. High levels of receptor mRNA were present in HSC from previously cryopreserved cord blood compared with HSC from fresh bone marrow and fresh cord blood. The HSC from cryopreserved cord blood are excellent candidates for gene therapy protocols.