The research team cautions that the work, done only in the laboratory, is years away from clinical use in patients, but should provide tools for developing gene therapies for SCD and a variety of other blood disorders.
In an article published online August 31 in Blood, the researchers say they are one step closer to developing a feasible cure or long-term treatment option for patients with SCD, which is caused by a single DNA letter change in the gene for adult hemoglobin, the principle protein in red blood cells needed to carry oxygen. People who inherited two copies — one from each parent — of the genetic alteration, the red blood cells are sickle-shaped, rather than round. The misshapen red blood cells clog blood vessels, leading to pain, fatigue, infections, organ damage and premature death.
Although there are drugs and painkillers that control SCD symptoms, the only known cure — achieved rarely — has been bone marrow transplant. But because the vast majority of SCD patients are African-American and few African-Americans have registered in the bone marrow registry, it has been difficult to find compatible donors, says Linzhao Cheng, Ph.D., a professor of medicine and associate director for basic research in the Division of Hematology and also a member of the Johns HopkinsInstitute for Cell Engineering. “We’re now one step closer to developing a combination cell and gene therapy method that will allow us to use patients’ own cells to treat them.”
Using one adult patient at The Johns Hopkins Hospital as their first case, the researchers first isolated the patient’s bone marrow cells. After generating induced pluripotent stem (iPS) cells — adult cells that have been reprogrammed to behave like embryonic stem cells — from the bone marrow cells, they put one normal copy of the hemoglobin gene in place of the defective one using genetic engineering techniques.
The researchers sequenced the DNA from 300 different samples of iPS cells to identify those that contained correct copies of the hemoglobin gene and found four. Three of these iPS cell lines didn’t pass muster in subsequent tests.
“The beauty of iPS cells is that we can grow a lot of them and then coax them into becoming cells of any kind, including red blood cells,” Cheng said.
In their process, his team converted the corrected iPS cells into immature red blood cells by giving them growth factors. Further testing showed that the normal hemoglobin gene was turned on properly in these cells, although at less than half of normal levels. “We think these immature red blood cells still behave like embryonic cells and as a result are unable to turn on high enough levels of the adult hemoglobin gene,” explains Cheng. “We next have to learn how to properly convert these cells into mature red blood cells.”
Only one drug treatment has been approved by the FDA for treatment of SCD, hydroxyurea, whose use was pioneered by George Dover, M.D., the chief of pediatrics at the Johns Hopkins Children’s Center. Outside of bone marrow transplants, frequent blood transfusions and narcotics can control acute episodes.
The research was funded by grants from the Maryland Stem Cell Fund and the National Institutes of Health, and a fellowship from the Siebel Foundation.
Authors on the paper are Jizhong Zou, Xiaosong Huang, Sarah Dowey, Prashant Mali and Cheng, all from The Johns Hopkins University.Media Contacts:
Vanessa McMains | EurekAlert!
A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich
New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
17.02.2017 | Medical Engineering
17.02.2017 | Medical Engineering
17.02.2017 | Health and Medicine