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HIV Stem Cell Research

Can stem cells cure HIV?

A promising new case report of stem cell therapy for leukemia re-opens the possibility of curing HIV infection with stem cell transplantation

Revisiting HIV and Stem Cells
by Ann A. Kiessling, PhD | Bedford Research Foundation | Winter 2009/2010

In February, 2009, a medical team in Germany (N Engl J Med 360(7):692; February 12, 2009) reported that their treatment for leukemia in an HIV-infected man may have cured his HIV disease. He was reported to be free of HIV 20 months after transplantation with bone marrow stem cells from a donor who was naturally resistant to HIV. This report has special meaning to Bedford Foundation scientists because of their core research area: patient-specific stem cells.

hiv stem cell
HIV may be cured by a bone marrow transplant similar to common treatments for leukemia.

A brief review:

HIV infects cells of the immune system, some of which reside in reservoirs, such as lymph nodes. Eradicating all HIV infected cells using methods developed for other diseased immune cells, e.g. cancers, is a highly promising treatment strategy.

There have, however, been two principle problems with this strategy: (1) bone marrow cells for transplantation must closely match the cells of the recipient to avoid the serious complication of "graft-versus-host-disease," in which the transplanted cells fight the body, and (2) the transplanted bone marrow cells become infected with HIV, which not only fails to cure the patient’s HIV disease, but is a wasted use of valuable bone marrow cells needed to treat cancers in non-HIV infected individuals.

Solving Problem 1: Stem Cell Research

The first problem would be solved by generating stem cells directly from the HIV-infected patient. Such patient-specific cells would be a perfect match, thus
avoiding the risk of graft-versus-host-disease.

What is a Parthenote Stem Cell? (1 min)
Unlike most embryonic stem cell research, the Foundation's research with Parthenotes does not require the use of fertilized human eggs.

Deriving patient-specific stem cells has been the focus of Bedford Research Foundation scientists for several years. Bedford Research is raising funds to continue the work of their scientists to derive stem cells from unfertilized eggs. Termed "parthenote stem cells" this research was begun in 2000, paused in 2004 to conduct more basic research to improve the efficiency of stem cell derivation, and the hope is to resume the work 2010. This work, which would provide patient-specific stem cells for younger women, cannot be federally funded.

In 2008, BRF scientists began studies to also derive patient-specific stem cells for men: from the testis. Work with mouse models has been very promising, and Bedford Research is now raising funds to develop methods to
derive stem cells from human testis, including men with HIV disease.

CCR5

In Humans, the CCR5 gene location is on the short (p) arm at position 21 on chromosome 3. Certain populations have inherited the Delta 32 mutation resulting in the Genetic deletion of the CCR5 gene. Homozygous carriers of this mutation are resistant to HIV-1 infection.
http://en.wikipedia.org/wiki/CCR5

Solving Problem 2: Resistance to HIV infection

HIV must bind to specific receptors, e.g. CCR5, on the surface of cells in order to infect them. People born with genetic defects in the CCR5 gene are resistant to infection by HIV. The German medical team used bone marrow stem cells lacking CCR5, and thus they were resistant to infection after transplantation. Methods for eliminating CCR5 expression are also under advanced stages of study. Work to date is very promising.

Research needed

Many research hurdles remain, but they can be surmounted. With proper funding, patient-specific stem cells lacking CCR5 could be developed by Bedford Research scientists in the near future. These cells would form the basis for an entirely new, potentially curative therapy for HIV disease. Personnel and supplies to move this project forward as fast as possible will cost $345,000 per year. Every donation counts.

 

 
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