PMID- 8788171
OWN - NLM
STAT- MEDLINE
DCOM- 19961022
LR  - 20061115
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 7
IP  - 2
DP  - 1996 Jan 20
TI  - Increased stable retroviral gene transfer in early hematopoietic progenitors 
      released from quiescence.
PG  - 207-13
AB  - It has been previously demonstrated that prestimulation with cytokines could 
      improve gene transfer in hematopoietic progenitors. However, we have shown that 
      no combination of cytokines so far tested is able to release rapidly in vitro the 
      stem cell compartment from quiescence unless an autocrine transforming growth 
      factor-beta 1 (TGF-beta 1) is blocked by specific oligonucleotide antisense or 
      antiserum (Hatzfeld et al., 1991, J. Exp. Med., 174, 925). We now report that a 
      10-hr cytokine prestimulation of SBA-CD34high human umbilical cord blood 
      progenitors increases retrovirally mediated transfer of the nls-lacZ reporter 
      gene from 1% to 23.8% and addition of anti-TGF-beta serum doubles this increase 
      (47.3%). Interestingly, the effect of anti-TGF-beta preincubation on gene 
      transfer is most effective on the most immature progenitors, which develop into 
      high proliferative potential mixed colonies with 1-2 x 10(5) cells. Anti-TGF-beta 
      serum pretreatment increases gene transfer in these early colony-forming units 
      granulocyte-erythroid-megakaryocyte-macrophage (CFU-GEMM) from 54.1% to 93.3%. It 
      augments significantly the stability of gene expression in all subpopulations of 
      mixed colonies. Colonies obtained after pretreatment with anti-TGF-beta serum are 
      larger and the expression of the stably integrated recombinant provirus does not 
      reduce their size. This prestimulation method provides a substantial improvement 
      for gene transfer efficiency within the quiescent stem cell compartment that is 
      responsible for long-term engraftment.
FAU - Hatzfeld, A
AU  - Hatzfeld A
AD  - Centre National de Recherche Scientifique, Villejuif, France.
FAU - Batard, P
AU  - Batard P
FAU - Panterne, B
AU  - Panterne B
FAU - Taieb, F
AU  - Taieb F
FAU - Hatzfeld, J
AU  - Hatzfeld J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Antigens, CD34)
RN  - 0 (Hematopoietic Cell Growth Factors)
RN  - 0 (Immune Sera)
RN  - 0 (Interleukin-6)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Antigens, CD34/analysis
MH  - Fetal Blood
MH  - Gene Expression
MH  - *Gene Transfer Techniques
MH  - Genes, Reporter/genetics
MH  - Hematopoietic Cell Growth Factors/pharmacology
MH  - Hematopoietic Stem Cells/*physiology
MH  - Humans
MH  - Immune Sera
MH  - Interleukin-6/pharmacology
MH  - Retroviridae/*genetics
MH  - Transforming Growth Factor beta/physiology
MH  - beta-Galactosidase/biosynthesis/genetics
EDAT- 1996/01/20 00:00
MHDA- 1996/01/20 00:01
CRDT- 1996/01/20 00:00
PHST- 1996/01/20 00:00 [pubmed]
PHST- 1996/01/20 00:01 [medline]
PHST- 1996/01/20 00:00 [entrez]
AID - 10.1089/hum.1996.7.2-207 [doi]
PST - ppublish
SO  - Hum Gene Ther. 1996 Jan 20;7(2):207-13. doi: 10.1089/hum.1996.7.2-207.