[Transgenic human thymopoiesis from retrovirally transduced umbilical cord blood hematopoietic stem cells: experimental studies in the SCID-hu mouse].
The gene encoding the CD2 mouse cell surface antigen was retrovirally transduced into cord blood CD34+ cells. On infection by culture at the contact of retrovirus-packaging cells, the mCD2 marker was expressed by 30-40% CD34+ cells, that included the most primitive stem cell-enriched Thy-1+ and CD38- subsets. Accordingly, sorted cord blood CD34+Thy-1+ cells could be directly infected in the same conditions. mCD2- transgenic cord blood CD34+ cells were then used to reconstitute human fetal thymus implanted in SCID mice. Five to 8 weeks later, the mCD2 antigen was detected on approximately 10% of the human thymocytes repopulating the thymus grafts and the transgene genome was detected in graft cell DNA by Southern blot. These results demonstrate efficient gene transfer into primitive cord blood hematopoietic cells endowed with lymphoid potential and suggest gene therapy schemes in neonates suffering inherited or acquired-such as HIV infection-disorders of the T-cell lineage.
Champseix
C
C
Institut d'Embryologie Cellulaire et Moléculaire, CNRS UPR 9064, Nogent-sur-Marne, France.
Maréchal
V
V
Khazaal
I
I
Defard
M
M
Schlegel
N
N
Vilmer
E
E
Lehn
P
P
Heard
J M
JM
Péault
B
B
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002472:Cell Transformation, Viral; D005312:Fetal Blood / Q000166:cytology; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D012190:Retroviridae; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology; D019076:Transgenes
D018952:Antigens, CD34; D005819:Genetic Markers