Use of blood outgrowth endothelial cells for gene therapy for hemophilia A
Blood, ISSN: 0006-4971, Vol: 99, Issue: 2, Page: 457-462
2002
- 151Citations
- 75Captures
- 1Mentions
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations151
- Citation Indexes151
- 151
- CrossRef132
- Captures75
- Readers75
- 75
- Mentions1
- Blog Mentions1
- Blog1
Article Description
A culture of human blood outgrowth endothelial cells (BOECs) was established from a sample of peripheral blood and was transfected using a nonviral plasmid carrying complementary DNA for modified human coagulation factor VIII (B domain deleted and replaced with green fluorescence protein). BOECs were then chemically selected, expanded, cryopreserved, and re-expanded in culture. Stably transfected BOECs were administered intravenously daily for 3 days to NOD/SCID mice at 4 cell dose levels (from 5 × 10 4 to 40 × 10 4 cells per injection). In 156 days of observation, mice showed levels of human FVIII that increased with cell dose and time. Mice in all cell dose groups achieved therapeutic levels (more than 10 ng/mL) of human FVIII, and mice in the 3 highest dose groups acquired levels that were normal (100-200 ng/mL) or even above the normal range (highest observed value, 1174 ng/mL). These levels indicate that the BOECs expanded in vivo after administration. When the mice were killed, it was found that BOEC accumulated only in bone marrow and spleen and that these cells retained endothelial phenotype and transgene expression. Cell doses used here would make scale-up to humans feasible. Thus, the use of engineered autologous BOECs, which here resulted in sustained and therapeutic levels of FVIII, may comprise an effective therapeutic strategy for use in gene therapy for hemophilia A.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0006497120383245; http://dx.doi.org/10.1182/blood.v99.2.457; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0037079740&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/11781225; https://ashpublications.org/blood/article/99/2/457/53409/Use-of-blood-outgrowth-endothelial-cells-for-gene; https://dx.doi.org/10.1182/blood.v99.2.457
American Society of Hematology
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