Unaltered repopulation properties of mouse hematopoietic stem cells transduced with lentiviral vectors.

Abstract:

:Recent studies of retroviral-mediated gene transfer have shown that retroviral integrations themselves may trigger nonmalignant clonal expansion of hematopoietic stem cells (HSCs) in transplant recipients. These observations suggested that previous conclusions of HSC dynamics based on gamma-retroviral gene marking should be confirmed with improved vectors having a more limited capacity to transactivate endogenous genes. Because of the low trans-activation activity of self-inactivating lentiviral vectors (LVs), we have investigated whether the LV marking of mouse HSCs induces a competitive repopulation advantage in recipients of serially transplants. As deduced from analyses conducted in primary and secondary recipients, we concluded that lentivirally transduced HSCs have no competitive repopulation advantages over untransduced HSCs. By linear amplification-mediated polymerase chain reaction (LAM-PCR) analysis, we characterized LV-targeted genes in HSC clones that engrafted up to quaternary recipients. Although 9 clones harbored integrations close to defined retroviral insertion sites, none was characterized as a common integration site, and none was present in HSC clones repopulating quaternary recipients. Taken together, our results show unaltered repopulation properties of HSCs transduced with LVs, and confirm early studies suggesting the natural capacity of a few HSC clones to generate a monoclonal or oligoclonal hematopoiesis in transplant recipients.

journal_name

Blood

journal_title

Blood

authors

Gonzalez-Murillo A,Lozano ML,Montini E,Bueren JA,Guenechea G

doi

10.1182/blood-2008-03-142661

subject

Has Abstract

pub_date

2008-10-15 00:00:00

pages

3138-47

issue

8

eissn

0006-4971

issn

1528-0020

pii

blood-2008-03-142661

journal_volume

112

pub_type

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