Protection of hematopoietic stem cells from chemotherapy-induced toxicity by multidrug-resistance 1 gene transfer.
An increased chemotherapeutic dose intensity is believed to translate into higher survival rates among cancer patients. Pancytopenia is the dose-limiting toxic result of most anticancer agents. Overexpression of the human multidrug resistance 1 (MDR1) gene in transgenic animals resulted in complete myeloprotection against high doses of cytostatic drugs. Stem cell research, vector development, and experimental pharmacology are uniting their efforts in an attempt to achieve a similar effect in human hematopoietic stem cells. This article gives an overview of the crucial steps involved, from retroviral vector design and optimization of viral titers to vector uptake, gene integration, and expression. The authors' own results are presented with special regard in vitro and in vivo assays for the detection of hematopoietic stem cell transduction.
Fruehauf
S
S
Department of Internal Medicine V, University of Heidelberg, Germany.
Wermann
K
K
Buss
E C
EC
Hundsdoerfer
P
P
Veldwijk
M R
MR
Haas
R
R
Zeller
W J
WJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000633:toxicity*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D012190:Retroviridae / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents