Credit: ThinkStock
Scientists at EPFL have demonstrated a new method that can be used to greatly improve the safety and efficiency of gene therapy using the patient's own stem cells.
Ex vivo gene therapy is a medical technique in which stem cells are taken from the patient, and their deficient genes are switched with healthy ones. The stem cells are grown in the lab and re-inserted into the patient. However, this method often has health risks, such as leukemia and mutations. The problem is that most stem cells cannot be grown efficiently with current technologies, and the resulting cell population in the lab can contain a mix of healthy and unhealthy cells. Scientists at EPFL have developed a selection process that can detect the cells that have take up the healthy genes with great specificity, greatly reducing the risks of ex vivo gene therapy. The method, successfully tested on cells from a skin disease, is published in EMBO Molecular Medicine.
Yann Barrandon at EPFL and Centre Hospitalier Universitaire Vaudois (CHUV) led a team of researchers that has developed a safe "clonal strategy" for ex vivo gene therapy that can be easily performed before cells are transplanted back into patients. The strategy uses a set of stringent quality control assays inspired from the protocols used by biotech companies and regulatory affairs to produce medicinal proteins through genetically engineered mammalian cells.
The quality control assays aim to satisfy several selection criteria before the cells are transplanted back into the patient. Specifically, the genetically modified stem cells must: show high growth potential; produce the protein needed to fight the disease; sustain long-term tissue regeneration in the patient; sustain long-term correction of the disease; not run the risk of forming tumors; have properly integrated the new genes into their genome and; not spread across the patient's body.
The researchers tested their strategy of criteria and assays on stem cells from the skin of a 4-year-old child suffering from a severe condition called dystrophic epidermolysis bullosa, which causes extremely fragile skin, and can even be lethal. The cells from the child were isolated, put through the quality control strategy and implanted in mice to see if they would cause tumors. After more than 100 days, no tumors were recorded.
The study shows that the safety and efficiency of ex vivo gene therapy depends on creating a homogeneous ("clonal") culture of cells rather than the more widely used mixed populations. This approach is more demanding, and Barrandon's lab is actually one of the few in the world who have successfully created and maintained single-cell stem cultures. However, the study is expected to open a new chapter in the use of gene therapy methodologies, making them safer and more efficient for patients.
The next step for the researchers is to test their method on actual patients and to develop tools to facilitate the transfer of the single cell technology to other laboratories. This work is ongoing in collaboration with EPFL engineers. They are now in the process of developing a pilot clinical trial. "This is a proof-of concept study," says Yann Barrandon. "But the greatest aspect is that now any clinical lab in the world can take our strategy and adapt it to the disease that they are targeting."
Explore further: Quality control for adult stem cell treatment
More information: "A single epidermal stem cell strategy for safe ex vivo gene therapy." EMBO Molecular Medicine 27 February 2015. DOI: 10.15252/emmm.201404353
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Credit: ThinkStock
Scientists at EPFL have demonstrated a new method that can be used to greatly improve the safety and efficiency of gene therapy using the patient's own stem cells.
Ex vivo gene therapy is a medical technique in which stem cells are taken from the patient, and their deficient genes are switched with healthy ones. The stem cells are grown in the lab and re-inserted into the patient. However, this method often has health risks, such as leukemia and mutations. The problem is that most stem cells cannot be grown efficiently with current technologies, and the resulting cell population in the lab can contain a mix of healthy and unhealthy cells. Scientists at EPFL have developed a selection process that can detect the cells that have take up the healthy genes with great specificity, greatly reducing the risks of ex vivo gene therapy. The method, successfully tested on cells from a skin disease, is published in EMBO Molecular Medicine.
Yann Barrandon at EPFL and Centre Hospitalier Universitaire Vaudois (CHUV) led a team of researchers that has developed a safe "clonal strategy" for ex vivo gene therapy that can be easily performed before cells are transplanted back into patients. The strategy uses a set of stringent quality control assays inspired from the protocols used by biotech companies and regulatory affairs to produce medicinal proteins through genetically engineered mammalian cells.
The quality control assays aim to satisfy several selection criteria before the cells are transplanted back into the patient. Specifically, the genetically modified stem cells must: show high growth potential; produce the protein needed to fight the disease; sustain long-term tissue regeneration in the patient; sustain long-term correction of the disease; not run the risk of forming tumors; have properly integrated the new genes into their genome and; not spread across the patient's body.
The researchers tested their strategy of criteria and assays on stem cells from the skin of a 4-year-old child suffering from a severe condition called dystrophic epidermolysis bullosa, which causes extremely fragile skin, and can even be lethal. The cells from the child were isolated, put through the quality control strategy and implanted in mice to see if they would cause tumors. After more than 100 days, no tumors were recorded.
The study shows that the safety and efficiency of ex vivo gene therapy depends on creating a homogeneous ("clonal") culture of cells rather than the more widely used mixed populations. This approach is more demanding, and Barrandon's lab is actually one of the few in the world who have successfully created and maintained single-cell stem cultures. However, the study is expected to open a new chapter in the use of gene therapy methodologies, making them safer and more efficient for patients.
The next step for the researchers is to test their method on actual patients and to develop tools to facilitate the transfer of the single cell technology to other laboratories. This work is ongoing in collaboration with EPFL engineers. They are now in the process of developing a pilot clinical trial. "This is a proof-of concept study," says Yann Barrandon. "But the greatest aspect is that now any clinical lab in the world can take our strategy and adapt it to the disease that they are targeting."
Explore further: Quality control for adult stem cell treatment
More information: "A single epidermal stem cell strategy for safe ex vivo gene therapy." EMBO Molecular Medicine 27 February 2015. DOI: 10.15252/emmm.201404353
Medical Xpress on facebook
Related Stories
Quality control for adult stem cell treatment
A team of European researchers has devised a strategy to ensure that adult epidermal stem cells are safe before they are used as treatments for patients. The approach involves a clonal strategy where stem cells are collected ...
Stem cell researchers develop promising method to treat sickle cell disease
UCLA stem cell researchers have shown that a novel stem cell gene therapy method could lead to a one-time, lasting treatment for sickle cell disease—the nation's most common inherited blood disorder.
New study shows safer methods for stem cell culturing
A new study led by researchers at The Scripps Research Institute (TSRI) and the University of California (UC), San Diego School of Medicine shows that certain stem cell culture methods are associated with increased DNA mutations. ...
Researchers engineer custom blood cells
Researchers at Johns Hopkins have successfully corrected a genetic error in stem cells from patients with sickle cell disease, and then used those cells to grow mature red blood cells, they report. The study ...
Gene therapy for human skin disease produces long-term benefits
Stem cell-based gene therapy holds promise for the treatment of devastating genetic skin diseases, but the long-term clinical outcomes of this approach have been unclear. In a study online December 26th in the ISSCR's journal ...
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Hidden burden: Most people carry recessive disease mutations
Humans carry an average of one to two mutations per person that can cause severe genetic disorders or prenatal death when two copies of the same mutation are inherited, according to estimates published today ...
More anti-inflammatory genes mean longer lifespans for mammals
We age in part thanks to "friendly fire" from the immune system—inflammation and chemically active molecules called reactive oxygen species that help fight infection, but also wreak molecular havoc over ...
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Scientists at A*STAR's Genome Institute of Singapore (GIS) have developed a new technique that simplifies the task of identifying the precise DNA mutations that cause disease, which lays the groundwork for ...
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Researchers at UT Southwestern Medical Center have uncovered how the body's inflammatory response can alter how estrogen promotes the growth of breast cancer cells.
New genetic clues emerge on origin of Hirschsprung's disease
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