stem cells
April 29, 2014

Researchers Create Personalized, Disease-Specific Stem Cells

redOrbit Staff & Wire Reports - Your Universe Online

Researchers reported on Monday the creation of the first disease-specific line of embryonic stem cells made with a patient’s own DNA, a major breakthrough in the field of regenerative medicine.

The achievement marks the first time cloning technologies have been used to generate stem cells that are genetically matched to adult patients.

The independent group of scientists, led by experts at the New York Stem Cell Foundation Research Institute (NYSCF), used somatic cell nuclear transfer to successfully clone a skin cell from a 32-year-old woman with type-1 diabetes. Those cells were then turned into insulin-producing cells resembling the beta cells lost in the disease.

In type-1 diabetes, a patient’s immune system attacks the body’s insulin-producing pancreatic beta cells, leaving the patient unable to adequately regulate blood sugar levels.

The researchers said the insulin-producing cells created in the current study could someday replace cells damaged by type-1 diabetes, something that could provide better treatment or even a cure for the disease.

"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 Solomon, CEO and co-founder of NYSCF, said in a recent statement.

"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.”

As reported Monday in the journal Nature, the scientists derived embryonic stem cells by adding the nuclei of adult skin cells to unfertilized donor oocytes using a process known as somatic cell nuclear transfer (SCNT). Embryonic stem cells were created from the adult donor with type-1 diabetes and a healthy control.

In 2011, the team reported creating the first embryonic cell line from human skin using nuclear transfer when they made stem cells and insulin-producing beta cells from patients with type-1 diabetes. However, those stem cells were triploid, meaning they had three sets of chromosomes, and therefore could not be used for new therapies.

In the latest work, researchers were able to overcome this final hurdle to making personalized stem cells by making a patient-specific embryonic stem cell line that had just two sets of chromosomes (a diploid state), the normal number in human cells.

It is the first successful derivation by SCNT of diploid pluripotent stem cells from adult and neonatal somatic 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 Dr. Egli, the NYSCF scientist who led the research and conducted many of the experiments.

"By reprograming 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."

Because the stem cells are made using a patient's own skin cells, the beta cells for replacement therapy would be autologous, or from the patient, matching the patient's DNA. However, generating autologous beta cells using SCNT is only the first step in developing a complete cell replacement therapy for type-1 diabetes, due to the fact that type-1 diabetes is a disease in which the body’s immune system attacks a patient’s beta cells. Because of this, further work is underway at NYSCF and other institutions to develop strategies to protect existing and therapeutic beta cells from also being attacked by the immune system, as well as to prevent such attacks.

In the current work, the scientists systematically analyzed the factors that affect stem-cell derivation after SCNT. The reprogramming of skin cells from a type-1 diabetes patient by SCNT has long been sought, but has been challenging to achieve because of logistical difficulties in obtaining human oocytes for research, as well as an incomplete understanding of the biology of human oocytes.

The scientists found that the addition of specific chemicals, called histone deacetylase inhibitors, and an efficient protocol for human oocyte activation were critical to achieving development to the stage at which embryonic stem cells are derived. As an additional optimization of the SCNT protocol, the scientists found that it was important to maintain the integrity of the plasma membrane during manipulation, and that to do so, the agent used in the manipulations had to be at a low dose.

The scientists applied their optimized protocol to skin cells of a male newborn and the cells of the adult woman with type-1 diabetes. From these two cell lines, the researchers produced a total of four SCNT-derived embryonic stem cell lines, all of which were diploid and could give rise to neurons, pancreatic cells, and cartilage, as well as various other cell types, demonstrating their pluripotency. Notably, the cells of the type-1 diabetes patient also gave rise to insulin-producing beta cells. Together with a separate paper published this month in the journal Cell Stem Cell by Chung et al., it is also the first report of diploid embryonic stem cell lines derived from a human after birth.

In addition to being the first report of the derivation of diploid pluripotent stem cells from a patient, when combined with the Cell Stem Cell paper, it is also the first report of diploid embryonic stem cell lines derived from a human after birth.

The researchers said the technique described in the Nature report can also be translated for use in the development of personalized autologous cell therapies for many other diseases and conditions, such as Parkinson's disease, macular degeneration, multiple sclerosis and liver diseases, in addition to replacing or repairing damaged bones.

Drs. Mitsutoshi Yamada and Bjarki Johannesson, postdoctoral fellows at the NYSCF Research Institute, were co-first authors of the report.