Abstract
A 32bp deletion in the chemokine receptor 5 (CCR5) gene (CMKBR5) was shown to be linked to HIV resistance. Bone marrow transplantation from the homozygous CCR5-del32 donor to a CDC Stage 2 HIV-positive recipient was demonstrated to confer a HIV resistance, resulting in discontinuation of antiretroviral therapy. In search for an unlimited source of CCR5-del32 cells for transplantation purposes, we tested 137 human embryonic stem cell (hESC) lines from the Reproductive Genetics Institute’s hESC lines collection, and report here the finding of 12 hESC lines with the CCR5-del32 allele, one of which represents a unique partenogenetic ESC line containing two copies of this deletion and may be studied for utility in stem cell transplantation treatment of HIV.
Highlights
The first HIV-positive individual has recently been successfully cured via bone marrow transplantation from the unrelated donor, who was chosen by human leukocyte antigen (HLA) matching, and for having a homozygous polymorphism in the chemokine receptor 5 (CCR5) gene CMKBR5 [1]
This paper presents the first results of the study, which revealed 12 human embryonic stem cell (hESC) lines containing this gene, of which one is unique parthenogenetic line with two copies of CCR5-del32
Using our ongoing practice of preimplantation genetic diagnosis (PGD), we initiated the development of the hESC lines with normal and abnormal genotypes [6,7], which were characterized by cytogenetic analysis, and a set of ESC criteria, including the presence of octamerbinding transcription factor-4 (Oct-4), tumor rejection antigen-2-39 (TRA-2-39), high molecular weight glycoproteins, and stage specific embryonic antigens (SSEA-3, SSEA-4)
Summary
The first HIV-positive individual has recently been successfully cured via bone marrow transplantation from the unrelated donor, who was chosen by human leukocyte antigen (HLA) matching, and for having a homozygous polymorphism in the chemokine receptor 5 (CCR5) gene CMKBR5 [1]. The use of unrelated umbilical cord blood (UCB), which is a valuable source of hematopoietic stem cells, is presently an established alternative to bone marrow transplantation.
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