UCSF Scientists Begin Studies to Create Cloned Human Embryos
by Jennifer O'Brien
UCSF scientists have begun studies aimed at creating cloned human embryos, using the technique known as somatic cell nuclear transfer (SCNT). If the process proves successful, it ultimately could be used to develop patient-specific human embryonic stem cell lines to study such diseases as Parkinson's disease, amyotrophic lateral sclerosis and heart disease.
The technique could also be used to develop patient-specific, cell-based therapies for a variety of diseases, and help to illuminate the first steps of human development.
The immediate challenge facing researchers at UCSF and the handful of other labs around the world that are pursuing this research, however, is to determine whether nuclear transfer can be carried out successfully with human cells.
In two papers published in 2004 and 2005, the South Korean team of now-discredited Woo Suk Hwang reported, first, that it had succeeded in creating cloned human embryos via nuclear transfer and, later, that it had derived patient-specific stem cell lines from cloned embryos.
Process Is Challenging
But with the revelation that these findings were fabricated, the scientific community finds itself back at the earliest stage of exploring the potential of the technology with human cells. "We do not know if somatic cell nuclear transfer will prove viable for creating cloned human embryos," says Arnold Kriegstein, MD, PhD, director of the UCSF Institute for Regeneration Medicine. "Certainly, the process presents significant challenges. "But we do feel that it is a strategy with enough potential that it needs to be examined fully, and broadly, by numerous labs. This is a new scientific frontier, and as with all science, it must be explored carefully, thoughtfully and rigorously." The research at UCSF is led by Renee Reijo Pera, PhD, co-director of the Human Embryonic Stem Cell Center. Reijo Pera and her colleagues are interested in using nuclear transfer as a step leading to the creation of patient-specific embryonic stem cell lines, both for study and for transplantation to treat damaged tissues. They are also interested in studying genetic reprogramming, which occurs when sperm meets egg. The goal of this work would be to identify the genetic missteps that sometimes occur in this process, leading to birth defects, some cases of infertility and the initial stages of some cancers. Somatic Cell Nuclear Transfer Primer
In somatic cell nuclear transfer, the two sets of DNA found in each of the body's cells (except sperm and egg, which each contain one set of DNA) are injected into an egg, or oocyte, from which the single set of DNA has been removed. The egg is then electrically stimulated and, in a process that is not understood, uses proteins or other materials within its fluid-filled membrane to instruct the newly inserted DNA to revert to the characteristics it would have in the embryonic state. The outcome, when successful, is a single-cell embryo - the same result achieved when egg and sperm meet during conception. In studies with animal cells, the resulting one-cell embryo begins dividing, and in the succeeding days evolves into a blastocyst, an amorphous ball of some 100 to 200 cells that contains embryonic stem cells. In human cells, however, scientists have had difficulty prompting the single-cell embryo to divide more than twice, and in only one case has an embryo reached the human blastocyst stage. Underscoring the challenge of human nuclear transfer studies, the South Korean team acknowledged that it had used at least 2,000 oocytes, donated from women, to try to achieve results. It is now known that whatever results they claimed were untrue. Still, some leading scientists believe the work should be pursued. Potential Value of Research
"The exploration of somatic cell nuclear transfer is at such an early stage that we can't predict the outcome of the research, but if it proves successful, it would offer significant insight into the earliest steps of human development, and serve as an important step in studying disease processes and developing novel therapies," says Reijo Pera. The goal of human nuclear transfer is to grow an embryo to the blastocyst stage, so that embryonic stem cells can be obtained and studied in the culture dish. If an embryo's DNA were to be obtained from a patient with a disease, such as Parkinson's disease, the disease itself could be studied. The stem cells could also serve as a starting point for trying to create specialized cells - brain, heart or pancreas cells, for example - that could be used in transplantation therapy. The UCSF study underway is aimed at determining whether nuclear transfer can be carried out successfully using oocytes either that have failed to fertilize following an attempt at in vitro fertilization (IVF) in the fertility clinic or that were too immature, when harvested in the IVF setting, to be used in fertility treatment. In either case, the oocytes are donated for this specific research by the patients. The donors are not compensated for their donations. If the studies prove unsuccessful over the course of months, but evidence suggests the research is still worth exploring, Reijo Pera will activate a second research study, currently under review, that would involve using normal oocytes donated by women specifically for SCNT research. Funding Challenges
The research is supported with private funds, and is conducted in laboratory space that does not receive federal funding, in keeping with current federal restrictions on human embryonic stem cell research. In the fall, the research will be moved into laboratory space currently being renovated with private funds to house the UCSF Human Embryonic Stem Cell Center. "The challenges in the field are financial, as well as scientific," notes Kriegstein. "We are still working to raise the funds to support the renovation project." UCSF is also raising funds to support the construction of a proposed building to house a significant portion of the overall UCSF Institute for Regeneration Medicine. Last month, Ray and Dagmar Dolby donated $16 million toward this proposed construction. UCSF's History in the Field
The nuclear transfer research represents UCSF's second investigation of the technology's potential. A small team of UCSF scientists conducted nuclear transfer studies with human cells in 1999 and again in 2001, but the researchers concluded that their results were unsuccessful, and they did not publish their findings at the time. These are believed to be the only US studies that have been conducted until now by a US university. The research was halted in part because the principal investigator of the research, Roger Pedersen, moved to Cambridge University, and in part because the remaining UCSF scientists focused their ongoing research on preparing their two human embryonic stem cell lines, which had qualified for inclusion in the National Institutes of Health Human Embryonic Stem Cell Registry for distribution to labs around the world. Since then, the cell lines have been shared with more than 70 labs. Links: UCSF & Stem Cells
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UCSF work cited in media nationwide recently, including NPR and NYT: National Public Radio New York Times Washington Post Wall Street Journal SF Chronicle |
But with the revelation that these findings were fabricated, the scientific community finds itself back at the earliest stage of exploring the potential of the technology with human cells. "We do not know if somatic cell nuclear transfer will prove viable for creating cloned human embryos," says Arnold Kriegstein, MD, PhD, director of the UCSF Institute for Regeneration Medicine. "Certainly, the process presents significant challenges. "But we do feel that it is a strategy with enough potential that it needs to be examined fully, and broadly, by numerous labs. This is a new scientific frontier, and as with all science, it must be explored carefully, thoughtfully and rigorously." The research at UCSF is led by Renee Reijo Pera, PhD, co-director of the Human Embryonic Stem Cell Center. Reijo Pera and her colleagues are interested in using nuclear transfer as a step leading to the creation of patient-specific embryonic stem cell lines, both for study and for transplantation to treat damaged tissues. They are also interested in studying genetic reprogramming, which occurs when sperm meets egg. The goal of this work would be to identify the genetic missteps that sometimes occur in this process, leading to birth defects, some cases of infertility and the initial stages of some cancers. Somatic Cell Nuclear Transfer Primer
In somatic cell nuclear transfer, the two sets of DNA found in each of the body's cells (except sperm and egg, which each contain one set of DNA) are injected into an egg, or oocyte, from which the single set of DNA has been removed. The egg is then electrically stimulated and, in a process that is not understood, uses proteins or other materials within its fluid-filled membrane to instruct the newly inserted DNA to revert to the characteristics it would have in the embryonic state. The outcome, when successful, is a single-cell embryo - the same result achieved when egg and sperm meet during conception. In studies with animal cells, the resulting one-cell embryo begins dividing, and in the succeeding days evolves into a blastocyst, an amorphous ball of some 100 to 200 cells that contains embryonic stem cells. In human cells, however, scientists have had difficulty prompting the single-cell embryo to divide more than twice, and in only one case has an embryo reached the human blastocyst stage. Underscoring the challenge of human nuclear transfer studies, the South Korean team acknowledged that it had used at least 2,000 oocytes, donated from women, to try to achieve results. It is now known that whatever results they claimed were untrue. Still, some leading scientists believe the work should be pursued. Potential Value of Research
"The exploration of somatic cell nuclear transfer is at such an early stage that we can't predict the outcome of the research, but if it proves successful, it would offer significant insight into the earliest steps of human development, and serve as an important step in studying disease processes and developing novel therapies," says Reijo Pera. The goal of human nuclear transfer is to grow an embryo to the blastocyst stage, so that embryonic stem cells can be obtained and studied in the culture dish. If an embryo's DNA were to be obtained from a patient with a disease, such as Parkinson's disease, the disease itself could be studied. The stem cells could also serve as a starting point for trying to create specialized cells - brain, heart or pancreas cells, for example - that could be used in transplantation therapy. The UCSF study underway is aimed at determining whether nuclear transfer can be carried out successfully using oocytes either that have failed to fertilize following an attempt at in vitro fertilization (IVF) in the fertility clinic or that were too immature, when harvested in the IVF setting, to be used in fertility treatment. In either case, the oocytes are donated for this specific research by the patients. The donors are not compensated for their donations. If the studies prove unsuccessful over the course of months, but evidence suggests the research is still worth exploring, Reijo Pera will activate a second research study, currently under review, that would involve using normal oocytes donated by women specifically for SCNT research. Funding Challenges
The research is supported with private funds, and is conducted in laboratory space that does not receive federal funding, in keeping with current federal restrictions on human embryonic stem cell research. In the fall, the research will be moved into laboratory space currently being renovated with private funds to house the UCSF Human Embryonic Stem Cell Center. "The challenges in the field are financial, as well as scientific," notes Kriegstein. "We are still working to raise the funds to support the renovation project." UCSF is also raising funds to support the construction of a proposed building to house a significant portion of the overall UCSF Institute for Regeneration Medicine. Last month, Ray and Dagmar Dolby donated $16 million toward this proposed construction. UCSF's History in the Field
The nuclear transfer research represents UCSF's second investigation of the technology's potential. A small team of UCSF scientists conducted nuclear transfer studies with human cells in 1999 and again in 2001, but the researchers concluded that their results were unsuccessful, and they did not publish their findings at the time. These are believed to be the only US studies that have been conducted until now by a US university. The research was halted in part because the principal investigator of the research, Roger Pedersen, moved to Cambridge University, and in part because the remaining UCSF scientists focused their ongoing research on preparing their two human embryonic stem cell lines, which had qualified for inclusion in the National Institutes of Health Human Embryonic Stem Cell Registry for distribution to labs around the world. Since then, the cell lines have been shared with more than 70 labs. Links: UCSF & Stem Cells