Dr. Janet Rossant to be keynote at 2011 Activated Egg Symposium

We’re delighted to report that Dr. Janet Rossant, Professor of Molecular Genetics, Obstetrics and Gynaecology, University of Toronto, and Chief of Research at the Hospital for Sick Children has graciously agreed to be our keynote speaker for the 2011 Activated Egg Symposium to be held Nov 4, 2011, at the Henderson House in Weston, MA.

Dr. Rossant is internationally recognized for her pioneering research in mouse genetics. Her major findings are related to the question of how genetically identical cells adopt distinct characteristics during embryo development.

In 2010, she received the Premeir’s Summit Award, and they made this video:

A little about more about Dr. Rossant:

Janet Rossant grew up in the UK and trained at the Universities of Oxford and Cambridge. When still a graduate student, she conducted now-classic work defining cell lineages and cell fates in the early mouse embryo. In 1977 Dr. Rossant moved to Canada and joined the faculty at Brock University. From 1985 to 2005, she was a researcher at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto. She joined the Hospital for Sick Children in 2005 and became the first female Head of its Research Institute since its founding in 1954. She is also a University Professor in the Department of Molecular Genetics at the University of Toronto.

Throughout her career, she has been a pioneer in manipulating the mouse embryo, deriving novel stem cell lines and interrogating the mouse genome. Most recently, building on her ongoing studies of the mouse blastocyst and the stem cells that arise from it, she is applying her developmental biology skills to derive definitive endoderm lineages from human embryonic stem cells and induced pluripotent stem cells.

As Chair of the Canadian Institutes of Health Research working group on stem cell research and as Deputy Scientific Director of the Canadian Stem Cell Network, Dr. Rossant continues to play a leadership role in setting Canada’s public policy regarding stem cell research.

She has received many accolades for her research, including being elected Fellow of the Royal Society of London (2000), and a Foreign Associate of the National Academies of Science, USA (2008). She was awarded the McLaughlin Medal of the Royal Society of Canada (1998), Eli Lilly/Robert L. Noble Prize from the National Cancer Institute of Canada (2000), Killam Prize for Health Sciences (2004), and FASEB Excellence in Science Award (2004). She received the 2007 March of Dimes Prize in Developmental Biology along with the late Dr Anne McLaren, and the 2007 Conklin Medal of the Society for Developmental Biology, of which she is a Past President.

Here’s another video biography by the Toronto Region Research Alliance in April, 2009:

Bedford presents Post Vasectomy Semen Analysis test kit at Mass Innovation Nights

Foundation Staff | May 24, 2011



As you may know, Bedford’s laboratory helps cover some of our overhead by offering a couple unique products — GEM and PVSA — that were developed as by-products of our research. PVSA, the newer of the two, was launched just 18 months ago.

PVSA is the first and only post-vasectomy test kit that provides CLIA certified laboratory results from a mail-in kit. This kit was developed using Bedford’s patented specimen fixative and mail-in kits for research.

The kit solves a vital problem for urologists: they are liable for their vasectomy surgeries until their patient’s surgery has been confirmed with two semen specimens.

The kit is inexpensive, easy to use, and helps doctors solve an almost 79% rate of non-compliance from patients. This solution has proven so powerful, we’ve more than tripled our number of clients in the last 10 months.

We are very proud to be presenting this innovative solution at Mass Innovation Nights on June 8, from 6-8:30 PM in Westborough. This event is free and open to the public. Please join us! Also, Mass Innovation Nights will select 4 of the 11 featured products to give a five minute presentation.



Video: Dr. Ann A. Kiessling receives first Alumni Achievement Award

From the University of Virginia:

The Alumni Achievement Award is a new award established in 2010.  It honors an alumna or alumnus who has shown superior achievement in a field other than nursing since graduating from the University of Virginia School of Nursing.  It recognizes distinction in one’s field and/or contributions to another profession, business or industry, government or public service, education, science or technology, or service to humanity.

2010 ACHIEVEMENT AWARD:  Ann Anderson Kiessling (BSN ’64)

Ann Anderson Kiessling received her BSN from U.Va. in 1964, BS in Chemistry and MS in Organic Chemistry from Central Washington University, and her PhD in Biochemistry from Oregon State University.  During the 1970s, her postdoctoral research explored relationships between viruses and cancer and led to the controversial discovery of Reverse Transcriptase in normal human cells. Believing that reverse transcription may play a role in early embryo development, she began to study eggs, sperm and early cleaving embryos.  Her expertise in reverse transcriptase and the reproductive tract led to the first studies of semen transmission of the AIDS virus in 1983, and in 1985 Harvard Medical School recruited her as Associate Professor in Obstetrics, Gynecology, & Reproductive Biology.  She is currently Associate Professor of Surgery.

In the 1990s, Ann combined her background in human egg biology and AIDS with her interest in stem cell research and founded the Bedford Stem Cell Research Foundation, in response to a controversial clinical research need that was best undertaken by an independent public charity.  The Foundation still receives no federal funding. There Ann developed the first program of assisted reproduction for couples living with HIV disease, and the first human egg donor program for stem cell research, a program that has become a model worldwide.  In 2003, she published Human Embryonic Stem Cells: An Introduction to the Science and Therapeutic Potential, the first textbook on the controversial topic. She has also published more than 100 scientific papers and given more than 60 lectures to audiences around the world. Her writings can be found in publications such as Nature, Lancet, Proceedings of the National Academy of Science and Connecticut Law Review, and she has been the focus of articles in The Boston Globe, Newsweek, and The Wall Street Journal.

Under Ann’s leadership, the Bedford Stem Cell Research Foundation has developed promising advances in deriving patient-specific stem cells while also tackling the moral and ethical issues in stem cell use.  Its programs have helped more than 120 couples affected by HIV disease have safe, healthy babies – and one day may lead to cures for spinal cord injuries, Parkinson’s, and HIV disease.

The First Five Days of a Mouse in GEM, Protein-Free Culture Medium

Foundation scientists are deriving new stem cell lines from fertilized mouse eggs in fully defined, protein-free culture medium, GEM (Gamete Embryo Medium). GEM is a specialized fluid that simulates fluids in the womb. The goal of these experiments is to improve the efficiency of deriving new stem cell lines from testis biopsies. By studying time lapse videos of developing mouse embryos, Foundation scientists will pinpoint the exact time to add stem cell growth factors to the culture medium.

Like all mammalian eggs, fertilized mouse eggs are huge cells that undergo several cleavage divisions before entering the uterus for further development. Each day is marked in this video, watch for these stages:

Day 1: Eggs are fertilized and cleave to the 2-cell stage
Day 2: 4-cell stage
Day 3: Morula (8 to 16 cells)
Day 4: Early blastocysts (40-60 cells)
Day 5: Hatching blastocysts (120-250 cells) This when the embryos could implant in the uterus for further development.

GEM, Bedford Research Foundation’s protein-free, chemically-defined embryo culture medium, supports the development of fertilized mouse eggs to blastocysts, the stage at which embryonic stem cells are derived. This unique culture medium has been more than 20-years in the making and is formulated based on the results of experiments designed to determine the most supportive in vitro conditions for assisted reproduction and embryo manipulation (references). The Foundation has made this medium available for research, academic and educational purposes – more info here.


Q & A with the Director about Stem Cell Research at the Foundation

Foundation Director, Ann A. Kiessling, PhD

This article is an excerpt from the Winter Newsletter (pdf).

Q: Has Obama’s Policy Helped Fund Stem Cell Research? 
A: President Obama’s executive order to rescind the restrictions on the number of stem cell lines that could be studied with federal funds was valuable for some studies, but as long as the Dickey-Wicker amendment controls federal funds, the development of stem cells from unfertilized eggs, a prime goal of Bedford Research scientists, cannot be federally funded.

Q: Why do patients need their own stem cells? 
A: The clinical trials that have provided “proof-of-principle” for cell-based therapies, e.g. transplantation of pancreatic cells for diabetes, have revealed that although some cells function normally, many fail because the transferred cels are rejected as “foreign.” The same is true for transplanted bone marrow in cancer therapies. If the stem cells were the patient’s own (i.e. patient-specific), they would not be rejected.

Q: Why do Bedford scientists work with parthenote and testis stem cells? 
A: Parthenote stem cells are derived from unfertilized human eggs, not embryos. Parthenote stem cells behave like embryonic stem cells in the laboratory, multiplying to the trillions needed for therapy, either for the egg donor herself, or for tissue-matched patients. Testis stem cells offer the possibility of deriving stem cells for every man in need, if they can be encouraged to multiply to the trillions possible with parthenote stem cells.

Q: How does Bedford Stem Cell Research Foundation fund its research? 
A: By private donations. The Foundation’s licensed clinical laboratory conducts highly specialized fee-for-service tests which cover the costs of the laboratory infrastructure. This allows research activities to proceed with minimal overhead. The lack of dependence on federal dollars also frees the Foundation from the administrative costs of separate accounting practices required by the Dickey-Wicker amendment.

Evidence for the cure of HIV infection by CCR5 – 32 stem cell transplantation

Kristina Allers,*, Gero Hütter, Jörg Hofmann, Christoph Loddenkemper, Kathrin Rieger, Eckhard Thiel and Thomas Schneider

Dec 2: Timothy Ray Brown can personally affirm that stem cells cure HIV disease, according to a December 2 report in the journal BLOOD. Mr. Brown, an HIV-positive American living in Germany, had leukemia and underwent chemotherapy and bone marrow transplantation in Berlin in 2007. His bone marrow match carried a rare gene mutation in the CCR5 receptor protein, rendering the transplanted cells resistant to HIV infection. Twenty months following the bone marrow transplant, the German team reported Mr. Brown’s leukemia appeared cured, and there was no evidence of HIV in his blood even though he had stopped his antiviral medication prior to the bone marrow transplant.

Now, a year later, the German team has re-examined Mr. Brown’s immune system for evidence of latent HIV infected cells, and found none. The uninfected transplanted bone marrow cells have replaced immune cells in all the parts of Mr. Brown’s body examined. This evidence is consistent with a cure of his HIV disease. Blood, Journal of the American Society of Hematology

This promising proof-of-principle success provides additional support for the patient-specific stem cell based therapy described in Bedford’s June Science Highlights.

ARTICLE ABSTRACT: HIV entry into CD4+ cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5{Delta}32/{Delta}32 stem cells. However, it was expected that the long-lived viral reservoir would lead to HIV rebound and disease progression during the process of immune reconstitution. In the present study, we demonstrate successful reconstitution of CD4+ T cells at the systemic level as well as in the gut mucosal immune system following CCR5{Delta}32/{Delta}32 stem cell transplantation, while the patient remains without any sign of HIV infection. This was observed although recovered CD4+ T cells contain a high proportion of activated memory CD4+ T cells, i.e. the preferential targets of HIV, and are susceptible to productive infection with CXCR4-tropic HIV. Furthermore, during the process of immune reconstitution, we found evidence for the replacement of long-lived host tissue cells with donor-derived cells indicating that the size of the viral reservoir has been reduced over time. In conclusion, our results strongly suggest that cure of HIV has been achieved in this patient.



The History of the Dickey-Wicker Amendment

Ann A. Kiessling, PhD

Federal concern with human embryo research began over 25 years ago with the advent of assisted reproduction technologies, i.e. in vitro fertilization (IVF) or “test tube babies.”

Although the first report of laboratory studies of human fertilization appeared in Science in 1944, (the work was conducted in Brookline, Massachusetts), clinical IVF was successful first in Great Britain in 1978 for couples with infertility. IVF became standard of care in the United States in the early 1980’s. As with all forms of clinical treatment, the medical community looked to basic science research to improve the safety and efficacy of IVF for mothers and babies.

In 1979, an Ethics Advisory Board for the National Institutes of Health issued guidelines for research on early human embryos, but no action was taken. The Federal Policy for the Protection of Human Subjects enacted in 1977 remained in place: 45CFR § 46.204(d), “No application or proposal involving human in vitro fertilization may be funded by the Department or any component thereof until the application or proposal has been reviewed by the Ethical Advisory Board and the Board has rendered advice as to its acceptability from an ethical standpoint.” Since there was no Ethics Advisory Board, federally funded research was not possible.

Throughout the 1980’s, public debate about conducting research on early human embryos took place in Great Britain. Many were in favor, many were opposed. The debate ultimately led to the formation of a regulatory body to oversee research on human fertilization. That regulatory body remains active today, which is why embryonic stem cell research was first possible in England.

In 1993, former President Bill Clinton initiated the National Institutes of Health Revitalization Act(Pub. L. No. 103-43), section 121(c) which simply eliminated 45CFR § 46.204(d), paving the way for Federal funding of grant applications to study human fertilization without the need for additional review by an Ethical Advisory Board.

When this possibility became known to the U.S. Congress in 1996, Representatives Jay Dickey and Roger Wicker authored a rider for the budget of the National Institutes of Health: Balanced Budget Downpayment Act, I, Public Law No 104-99, § 128, 110 Stat. 26, 34 “…none of the funds appropriated shall be used to support any activity involving: 1) the creation of a human embryo or embryos for research purposes; or 2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 C.F.R 46.208(a)(2) and section498(b) of the Public Health Service Act (42 USC 289g(b).” Further, “For purposes of this section, the term ‘human embryo or embryos’ includes any organism, not protected as a human subject under 45 CFR 46 as of the date of the enactment of this ACT, that is derived by fertilization, parthenogenesis, cloning, or any other means from one or more human gametes or human diploid cells.”

The Dickey-Wicker amendment to the budget of the National Institutes of Health has been renewed each year since 1996. Both men are currently active in the U.S. congress. Jay Dickey is a Congressman from Arkansas and Roger Wicker is a Senator from Mississippi. Neither President Bush’s nor President Obama’s Executive Order changed this Federal moratorium. (see August 24, 2010: Preliminary Injunction)

Given the wide-spread support among U. S. citizens for human embryonic stem cell research, it seems highly likely that broad public debate could convince congress that the will of the people is to allow taxpayer dollars to conduct research on the use of embryonic stem cells for regenerative medicine.

Until that time, private and state funding seems imperative to move this promising field forward. Increasing tax benefits for philanthropists who donate to stem cell research would help bridge the current gap in funding between the number of U.S. scientists capable and eager to conduct the necessary research, and the funding currently available.

For additional information, see the Connecticut Law Review, Vol 36, #4, 2004 that contains 8 essays on “What is an Embryo?” and the Rejoinder, Connecticut Law Review, Vol 37, #1, 2004.



Preliminary Injunction against Federal Funds for Stem Cell Research: What does it mean?

Ann A. Kiessling, PhD

Judge Lamberth’s Preliminary Injunction against Federal Funds for Stem Cell Research: What does it mean?

On August 23, 2010, U. S. District Court Judge Royce Lamberth issued a preliminary injunction against the use of federal funds for human embryonic stem cell research. If upheld, this injunction would reverse the executive orders of both former President George W. Bush, issued August 9, 2001, and President Barack Obama, issued March 9, 2009. Because of a long-standing prohibition on federal funding for research on human eggs and embryos (see “The History of the Dickey-Wicker amendment for a description of the Amendment“), Mr. Bush was the first U. S. president to release federal funds for research on human embryonic stem cell lines. His executive order restricted funds to research on those cell lines created prior to his order, in order to ensure that no tax payer dollars were used to create new cell lines by the destruction of human embryos. President Obama’s 2009 order eliminated Mr. Bush’s restrictions on eligible stem cell lines, thus allowing federal funds to study “to the extent permitted by law” all stem cells derived according to strict research guidelines issued by the National Institutes of Health (NIH).

Therefore, before Judge Lamberth’s preliminary injunction, according to new NIH guidelines, federal funds could be used to study any embryonic stem cells derived from human embryos, as long as the embryos had been donated for the research under strict guidelines, but tax payer dollars could still NOT be used to derive new embryonic stem cells. A surprising restriction was the prohibition against federal funds to both study and derive stem cell lines from unfertilized eggs. Termed parthenote stem cells, the stem cells derived from unfertilized eggs also promise to be useful for regenerative medicine, and do not carry the ethical concerns related to the destruction of embryos. (See the State of the Stem Cell)

The impact of Judge Lamberth’s preliminary injunction on on-going federally funded human embryonic stem cell research is not clear, nor has it been tallied how many scientists will be stalled in their efforts. The NIH indicates budgeting approximately $130 million annually for embryonic stem cell research, a small fraction of it’s $30 billion dollar annual budget. California’s Institute for Regenerative Medicine has a larger budget for stem cell research. Other states have set up programs to support stem cell research and bridge the gap in federal funding, including Connecticut, Illinois, Maryland, Massachusetts, New Jersey, New York and Ohio, but funding is only stable in California. Now, more than ever before, private philanthropic support is essential to the U.S. effort in embryonic stem cell research.

Given the wide-spread support among U. S. citizens for human embryonic stem cell research, it seems highly likely that broad public debate could convince congress that the will of the people is to allow taxpayer dollars to conduct research on the use of embryonic stem cells for regenerative medicine.

Until that time, private and state funding seems imperative to move this promising field forward. Increasing tax benefits for philanthropists who donate to stem cell research would help bridge the current gap in funding between the number of U.S. scientists capable and eager to conduct the necessary research, and the funding currently available.


2010 ISSCR: a remarkable lack of new clinical trials for stem cell therapy announced

isscr 2010 meetingThis past week (June 16-19) in San Francisco, Bedford Research Foundation had a booth at the ISSCR (International Society for Stem Cell Research) 8th annual conference.

We joined over 3,500 scientists, students and advisers attending the meeting from around the world. The conference boasted more than 200 talks, and some eye opening research from scientists such as Fred Gage, Salk Institute and George Daley, Children’s Hospital, Boston.

However, there was a remarkable lack of new clinical trials for stem cell therapy being announced, and no reports about recent discoveries of the importance of Circadian Rhythms in cell development.

And although several talks focused on the importance of “niche environment” to cell differentiation (the process of transforming stem cells into brain cells, skin cells, heart cells, etc.) none focused on the importance of “equivalence groups” in the early stages of development.

“Equivalence groups” are groups of cells that elect to work together to develop a specific tissue (e.g. heart or lung), and are able to communicate about the complex sequence of steps involved. Cells in an “equivalence group” will not opt to move to the next step of development, until the previous step has been completed successfully.

We hope that at the ISSCR 2011 we’ll see more talks featuring studies about how these groups communicate, as well as analysis of the sequences they are programmed to complete.