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Customizing stem cells
05-13-2014
by Kelsey Kaustinen  |  Email the author
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A research team led by Dr. Dieter Egli of the New York Stem Cell Foundation (NYSCF) Research Institute and Dr. Mark Sauer of Columbia University Medical Center has announced the creation of the first disease-specific embryonic stem cell line bearing two sets of chromosomes. This represents the first successful attempt at deriving diploid pluripotent stem cells from adult and neonatal somatic cells by way of SCNT. The embryonic stem cells were created from one adult donor with type 1 diabetes and a healthy control.
 
As patients with type 1 diabetes lack the beta cells that produce insulin, being able to produce such cells from stem cells for transplantation has potential as a treatment or possibly a cure for this subset of diabetes. And since the stem cells are produced from a patient’s own skin cells, the resultant beta cells would be autologous, bypassing any issues of incompatibility.
 
The research began in 2006 in hopes of developing patient-specific embryonic stem cell lines from patients with type 1 diabetes. The initial experiments were performed at Harvard University and the skin biopsies at Columbia, but due to federal and restrictions related to stem cell research, the work was moved to the NYSCF laboratory in 2008.
 
The team created the first embryonic cell line from human skin through nuclear transfer—adding the nuclei of adult skin cells to unfertilized donor oocytes (immature egg cells) via somatic cell nuclear transfer (SCNT)—in 2011, resulting in stem cells and insulin-producing beta cells from type 1 diabetes patients. Unfortunately, the stem cells were triploid, rendering them unusable for therapies. The new stem cell line, however, is diploid—containing only two sets of chromosomes, like natural cells.
 
“I am thrilled to say we have accomplished our goal of creating patient-specific stem cells from diabetic patients using somatic cell nuclear transfer,” Susan L. Solomon, CEO and co-founder of NYSCF, commented in a press release. “I became involved with medical research when my son was diagnosed with type 1 diabetes, and seeing today’s results gives me hope that we will one day have a cure for this debilitating disease. The NYSCF laboratory is one of the few places in the world that pursues all types of stem cell research. Even though many people questioned the necessity of continuing our SCNT work, we felt it was critical to advance all types of stem-cell research in pursuit of cures. We don’t have a favorite cell type, and we don’t yet know what kind of cell is going to be best for putting back into patients to treat their disease.”
 
The researchers also investigated the factors that influence stem-cell derivation after SCNT, and found that the addition of specific chemicals known as histone deacetylase inhibitors and an efficient protocol for human oocyte activation proved critical to achieving development to the stage at which embryonic stem cells can be derived. Another way to optimize the SCNT protocol was the maintenance of the integrity of the plasma membrane during manipulations, which required a low dose of the agent used in said manipulations. Using this optimized protocol, the team generated four SCNT-derived embryonic stem cell lines from the skin cells of a newborn and those of an adult with type 1 diabetes. All the resultant cell lines proved to be diploid and capable of differentiating to neurons, pancreatic cells and cartilage, with the cells of the diabetes patient also giving rise to insulin-producing beta cells.
 
“From the start, the goal of this work has been to make patient- specific stem cells from an adult human subject with type 1 diabetes that can give rise to the cells lost in the disease,” said Egli. “By reprogramming cells to a pluripotent state and making beta cells, we are now one step closer to being able to treat diabetic patients with their own insulin-producing cells.”
 
The work won’t stop here by any stretch, as a lack of beta cells is not the only issue presented by diabetes. Part of the problem is that the immune system attacks beta cells in cases of type 1 diabetes, so additional work is needed to determine a method of protecting beta cells—natural or transplanted—from the immune system. In addition, this technique is also applicable for a number of other diseases and conditions, including Parkinson’s disease, multiple sclerosis, macular degeneration, liver disease and the repair of damaged bones.
 
“This project is a great example of how enormous strides can be achieved when investigators in basic science and clinical medicine collaborate. I feel fortunate to have been able to participate in this important project,” said Sauer, vice chair of the Department of Obstetrics and Gynecology, professor of obstetrics and gynecology and chief of reproductive endocrinology at Columbia University Medical Center and program director of assisted reproduction at the Center for Women’s Reproductive Care.
 
Drs. Mitsutoshi Yamada and Bjarki Johannesson, postdoctoral fellows at the NYSCF Research Institute, were co-first authors of the paper, titled “Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells.” The work appeared online in Nature on April 28.
 
Code: E05141405

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