| |
|
|
|
|
|
|
|||
|
Blood, 1 August 2005, Vol. 106, No. 3, pp. 893-898. Prepublished online as a Blood First Edition Paper on April 21, 2005; DOI 10.1182/blood-2004-07-2859.
HEMATOPOIESIS Efficient marking of human cells with rapid but transient repopulating activity in autografted recipientsFrom the Department of Internal Medicine I, Albert-Ludwigs-University, Freiburg, Germany; the Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University, Freiburg, Germany; the Johanniter Hospital Rheinhausen, Duisburg, Germany; the Terry Fox Laboratory, British Columbia Cancer Agency and Department of Medical Genetics, University of British Columbia, Vancouver BC, Canada; and the Experimental Hematology Research Foundation, Molecular and Gene Therapy Program, Cincinnati Children's Hospital, Cincinnati, OH.
Short-term hematopoietic reconstituting cells have been identified in mice, nonhuman primates, and among human cells that engraft xenogeneic hosts. We now present clonal marking data demonstrating a rapid but unsustained contribution of cultured human autografts to the initial phase of hematologic recovery in myeloablated patients. Three patients received transplants of granulocyte colony-stimulating factormobilized autologous peripheral blood (PB) cells, of which a portion (8%-25% of the CD34+ cells) had been incubated in vitro with growth factors (5 days) and clinical grade LN retrovirus (3-5 days). More than 9% of the clonogenic and long-term culture-initiating cells harvested were transduced. Semiquantitative and linear amplification-mediated polymerase chain reaction analyses of serial PB samples showed that marked white blood cells appeared in all 3 patients within 11 days and transiently constituted up to 0.1% to 1% of those produced in the first month. However, within another 2 to 9 months, marked cells had permanently decreased to very low levels. Analysis of more than 50 vector insertion sites showed none of the clones detected in the first month were active later. Eighty percent of inserts were located within or near genes, 2 near CXCR4. These findings provide direct evidence of cells with rapid but transient repopulating activity in patients and demonstrate their efficient transduction in vitro.
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Copyright © 2005 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||