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Researchers generate patient-specific stem cells

Published on May 20, 2005 at 7:53 AM · No Comments

Researchers have isolated the first human embryonic stem cell lines specifically tailored to match the nuclear DNA of patients, both males and females of various ages, suffering from disease or spinal cord injury.

The research is being released by the journal Science, which is published by American Association for the Advancement of Science (AAAS), the non-profit science society, on the Science Express website.

These cell lines will enable the study of human disease in cells in the laboratory. The work also moves scientists one step closer to the goal of transplanting healthy cells into humans to replace cells damaged by diseases such as Parkinson's and diabetes.

Each of the 11 new human embryonic stem cell lines was created by transferring the nuclear genetic material from a non-reproductive cell of a patient into a donated egg, or "oocyte," whose nucleus had been removed. This method is called "somatic cell nuclear transfer" or SCNT. Next, oocytes with the patient's genetic material were allowed to grow to the blastocyst stage, an early stage of embryo development. Stem cells were then derived from the inner cell mass of the blastocyst. In laboratory culture, these cell lines displayed signs of immunological compatibility with the patients' cells, Science authors reported.

Oocyte donors and patients who donated non-reproductive cells were all unpaid volunteers. All donors signed informed-consent agreements. For underage donors of non-reproductive cells, both parents signed informed-consent agreements.

Before patient-specific stem cells can potentially be used in the clinic, a variety of issues must be addressed, the researchers emphasized. The stem cell lines produced from patients with disease will likely display characteristics of the disease, so they will probably not be appropriate for direct use in treating patients. In addition, researchers must develop methods to efficiently direct the differentiation of embryonic stem cells to specific stable cell types. Scientists must also find a way to remove the remaining animal components from the laboratory procedures. Currently, the procedure for isolating non-reproductive cells for the nuclear transfer method involves animal enzymes and serum.

In a Science "Policy Forum" related to the team's latest findings, David Magnus and Mildred Cho from Stanford University in Palo Alto, CA discuss international oversight and ethical issues in oocyte donation, including the need to promote realistic expectations of the outcomes of stem cell research.

The Korean researchers who performed this stem cell research improved upon their protocols that yielded the first embryonic stem cell line from a cloned human blastocyst. (Science 12 March 2004; 303: 1669-1674; published online 12 February 2004.)

In their new paper, Science author Woo Suk Hwang from Seoul National University in Seoul, Korea and colleagues replaced the nuclei from donated oocytes with nuclei from skin cells from male and female patients, ranging in age from 2 to 56, who had spinal cord injuries, juvenile diabetes and the genetic disease "congenital hypogamma-globulinemia."

From the 185 donated oocytes, endowed with the genetic material from a different person (or in one case, the same person), the researchers report development of 31 hollow balls of cells called "human nuclear-transfer blastocysts."

From the 31 nuclear-transfer blastocysts, the scientists derived 11 stem cell lines. The researchers generated these stem cell lines ten times more efficiently than in their 2004 Science study, using improved laboratory methods.

The single cell line generated in the 2004 Science paper resulted from nuclear transfer in which the oocyte and non-reproductive ("somatic") cell came from the same healthy female.

The new study produced a similar cell line from a woman who donated both the somatic cell and the oocyte; however, the donor was a spinal cord patient.

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