Can stem cells cure HIV?

Ann A. Kiessling, PhD

 

A promising new case report of stem cell therapy for leukemia re-opens the possibility of curing HIV infection with stem cell transplantation

Revisiting HIV and Stem Cells

In February, 2009, a medical team in Germany (N Engl J Med 360(7):692; February 12, 2009) reported that their treatment for leukemia in an HIV-infected man may have cured his HIV disease. He was reported to be free of HIV 20 months after transplantation with bone marrow stem cells from a donor who was naturally resistant to HIV. This report has special meaning to Bedford Foundation scientists because of their core research area: patient-specific stem cells.

hiv stem cell
HIV may be cured by a bone marrow transplant similar to common treatments for leukemia.

A brief review:
HIV infects cells of the immune system, some of which reside in reservoirs, such as lymph nodes. Eradicating all HIV infected cells using methods developed for other diseased immune cells, e.g. cancers, is a highly promising treatment strategy.

There have, however, been two principle problems with this strategy:(1) bone marrow cells for transplantation must closely match the cells of the recipient to avoid the serious complication of “graft-versus-host-disease,” in which the transplanted cells fight the body, and (2) the transplanted bone marrow cells become infected with HIV, which not only fails to cure the patient’s HIV disease, but is a wasted use of valuable bone marrow cells needed to treat cancers in non-HIV infected individuals.

Solving Problem 1: Stem Cell Research

The first problem would be solved by generating stem cells directly from the HIV-infected patient. Such patient-specific cells would be a perfect match, thus
avoiding the risk of graft-versus-host-disease.

What is a Parthenote Stem Cell? (1 min)
Unlike most embryonic stem cell research, the Foundation’s research with Parthenotes does not require the use of fertilized human eggs.

Deriving patient-specific stem cells has been the focus of Bedford Research Foundation scientists for several years. Bedford Research is raising funds to continue the work of their scientists to derive stem cells from unfertilized eggs. Termed “parthenote stem cells” this research was begun in 2000, paused in 2004 to conduct more basic research to improve the efficiency of stem cell derivation, and the hope is to resume the work 2010. This work, which would provide patient-specific stem cells for younger women, cannot be federally funded.

In 2008, BRF scientists began studies to also derive patient-specific stem cells for men: from the testis. Work with mouse models has been very promising, and Bedford Research is now raising funds to develop methods to
derive stem cells from human testis, including men with HIV disease.

CCR5

In Humans, the CCR5 gene location is on the short (p) arm at position 21 on chromosome 3. Certain populations have inherited the Delta 32 mutation resulting in the Genetic deletion of the CCR5 gene. Homozygous carriers of this mutation are resistant to HIV-1 infection.
http://en.wikipedia.org/wiki/CCR5

Solving Problem 2: Resistance to HIV infection

HIV must bind to specific receptors, e.g. CCR5, on the surface of cells in order to infect them. People born with genetic defects in the CCR5 gene are resistant to infection by HIV. The German medical team used bone marrow stem cells lacking CCR5, and thus they were resistant to infection after transplantation. Methods for eliminating CCR5 expression are also under advanced stages of study. Work to date is very promising.

Research needed

Many research hurdles remain, but they can be surmounted. With proper funding, patient-specific stem cells lacking CCR5 could be developed by Bedford Research scientists in the near future. These cells would form the basis for an entirely new, potentially curative therapy for HIV disease. Personnel and supplies to move this project forward as fast as possible will cost $345,000 per year. Every donation counts.

Bedford Research Foundation 2009 Newsletter

Read about all of the progress and the research that has occurred at the Foundation over the course of the past year! Dr. Kiessling outlines her vision for the upcoming year as well. Thank you for your support.


BSCRF Discovers Stem Cells Have A Clock

Genes called circadian oscillators control the body’s response to light and dark

All living things respond to the earth’s light/dark cycle. Many scientists believe that early organisms survived better if they replicated their genetic material, DNA, at night to avoid damage inflicted by ultra-violet rays from the sun. Darkness is accompanied by decreased temperatures, so all living things also go through daily (circadian) temperature changes, some imposed by environment (e.g. things that live in water), some by core body temperature changes stimulated by the brain.

The response of humans to circadian changes is controlled by light stimulation of sensors in the eye that coordinate the release of hormones by the brain. Patterns of sleep and wake are the best studied circadian responses.

More recent research has revealed that in addition to the circadian rhythm of the brain, all tissues in the body have their own circadian rhythm. Thus, the new findings indicate that every cell in the body has its own internal Clock, kept in synchrony by cycles of light and dark. Bedford Research Foundation stem cell scientists have used new technologies to study the human embryo cells that give rise to embryonic stem cells. The goal of the work is to fill information gaps about how stem cells multiply and differentiate into all the tissues in the body. These studies have revealed CLOCK genes may play an important role in stem cell biology, suggesting that new ways to culture stem cells in laboratories are urgently needed.

 

What is a Stem Cell?

A reserve cell with the capacity to multiply when needed to replace dead or damaged adult cells. Reserve stem cells do not exist for many vital tissues, including: heart, spinal cord, brain and pancreas.

Key Term “Pluripotent”

The capacity to become any cell in the body. Embryonic stem cells are pluripotent, adult stem cells are not.

Types of Pluripotent Stem Cells

Embryonic stem cells from fertilized eggs are good models for research, but they have ethical issues, and will have tissue rejection problems (similar to bone marrow and kidney transplants).

Parthenote stem cells (derived from unfertilized eggs) are as pluripotent as embryonic stem cells, and have been the focus of BSCRF scientists for several years. Studies using monkey parthenote stem cells to treat Parkinson’s disease in monkeys have been very promising.

  • Parthenotes do not have the potential tissue rejection problems faced by stem cells derived from fertilized eggs.
  • Unlike adult stem cells, parthenotes can become any cell in the body.
  • Less controversial than stem cells that are derived from fertilized eggs.

Induced pluripotent stem cells (derived from adult skin cells) were first reported by a Japanese research team in 2007. The genes of normal human cells can be manipulated in the laboratory to acquire properties of embryonic stem cells. Termed induced pluripotent stem cells, these cells have been useful research tools, but their gene manipulations limit their use for patient therapies. Many laboratories are studying ways to derive induced pluripotent stem cells without manipulating genes.

What Is An Embryonic Stem Cell?

A stem cell derived from eggs fertilized by sperm; these stem cells are “pluripotent.” Recent research has shown that it is also possible to get pluripotent stem cells from unfertilized eggs (parthenotes).

What Are Cord Blood Stem Cells?

Cells in the umbilical cord are “multipotent” and can give rise to all the cells in a normal bone marrow. Scientists are working to discover if these cells can become other types of adult stem cells.

What is an Adult Stem Cell?

Adult stem cells are stored in some tissues in the body to replace dead or damaged cells. For example: Skin has a large reserve supply of skin stem cells. They multiply only when needed.

Stem Cells From Unfertilized Eggs!!

When eggs are fertilized by sperm they become “activated,” their cells divide and can be a source of embryonic stem cells. Human eggs can also be “activated” without being fertilized. Unfertilized, “activated” eggs are called Parthenotes.

Egg Activation happens spontaneously in nature, but the process is not well understood. Research has found that unfertilized eggs can be activated either by (1) an electrical jolt or by (2) chemical stimulation. If successfully activated, the egg undergoes early cell divisions similar to fertilized eggs, but cannot give rise to an offspring.

After approximately 6 days the parthenote reaches the 150 cell Blastocyst stage and the stem cells can be moved to a separate dish to grow in a colony.

Results at BSCRF are promising. We have developed laboratory conditions that lead to mouse parthenote stem cells (mPS) with the same efficiency as from fertilized mouse eggs. Our most recent mPS cells were developed entirely in laboratory conditions free of other animal cells, thus paving the way for similar development of human PS cells free of animal products.

 

The 2009 Activated Egg Symposium

On November 6, 2009, the Foundation will host it’s seventh annual Activated Egg Symposium. During this one-day event researchers studying eggs for stem cell derivation, or reproduction share and discuss their research. With attendance limited to 100 the event provides a uniquely focused environment for investigators from academia and industry to meet and form collaborations.

This year’s keynote will be Dr. Renee A. Reijo Pera, director of Stanford’s Center for Human Embryonic Stem Cell Research and Education.

 

The 2009 Spinal Cord Workshop

“What are the Barriers to Cure?” the second spinal cord workshop was held on April 4th, 2009.

The workshop brought together medical and scientific expertise to identify barriers to reversal of the neurologic damage that follows spinal cord injury, and describe what is needed to overcome those barriers to cure.

The emerging field of stem cell therapy may hold special promise, but as described by the workshop participants, specifics about cell differentiation, method of delivery and outcome measures need to be developed.

 

Bake Sale For Stem Cell Research

In May of 2009 the Foundation received a donation from the members of the Purple Team Congress at Pennichuck Middle School in Nashua, New Hampshire raised during a bake sale.

“…because we know it could save many lives. Several people in our school have been affected by diseases that could be helped with further stem cell research.”

The bake sale raised $175 for the Bedford Research Foundation’s science programs. That is enough to cover a full day of reagents and supplies for Foundation’s staff to conduct experiments, and helps to fund further breakthroughs as we lead the way in this rapidly evolving area of biomedicine.

 

Foundation Research Programs

Patient-Specific Pluripotent Stem Cells

Developing patient-specific pluripotent stem cells is a primary focus of the Foundation’s Stem Cell Research program. Unfertilized eggs are an excellent, but underutilized source of pluripotent stem cells because of the moratorium on federal funding for the research. The new stem cell research guidelines, developed in response to President Obama’s executive order, still do not allow federal funding for research on stem cells derived from unfertilized human eggs.

Spinal Cord Injury Treatment Trials in the U.S.

The Spinal Cord Workshops in 2008 and 2009 organized by the Bedford Research Foundation with the University of Georgia and The Shepherd Center brought together clinicians and scientists in an unusually candid discussion of “What are the barriers to cure for spinal cord injury.” The 2010 workshop is planned for Taiwan and will also include Chinese clinicians and scientists. The goal is to expedite safety trials for stem cell therapy of spinal cord injury in the U. S. as well as China.

 

Letter From The Director

While stem cell scientists struggle to understand the therapeutic potential of the extraordinary cells that can multiply to the trillions needed for therapies, and become every tissue in the body, the public agonizes over the use of embryos to derive them. The result is a lack of federal funds for most of the work, despite President Obama’s executive order to rescind former President Bush’s restrictions. In fact, fewer federal dollars are available now than ever before while the National Institutes of Health (NIH) implements new guidelines. This is an enormous frustration for scientists, and an outright tragedy for patients.

Regrettably, the federal moratorium also extends to stem cells derived from eggs not fertilized by sperm, termed parthenote stem cells. It is a fact of nature that unfertilized human eggs can spontaneously (or artificially) begin to divide into cells that can also multiply to the trillions needed for therapies, and become all the types of cells in the body, but cannot become offspring. Parthenote stem cells would logically seem to avoid the dilemmas associated with stem cells from embryos, as well as provide a source of patient-specific stem cells for women. But the new NIH guidelines specifically exclude parthenote stem cells from federal funding. Therefore, the only source of funding for BSCRF’s unique parthenote stem cell research program is private contributions. Every dollar counts, $175 a day funds a stem cell researcher.

Not excluded, however, is the derivation of stem cells from testis, a break-through reported by several research teams in 2009. Apparently as versatile as embryonic stem cells, testis-derived stem cells are an exciting new source of pluripotent stem cells and patient-specific cells for men.

Award-winning Bedford Foundation stem cell scientists are poised to study both testis-derived and egg-derived stem cells in 2010 to determine if circadian laboratory conditions improve the yield of therapeutic cells for diseases such as spinal cord injury, diabetes, heart failure, lung failure, Parkinson’s disease, stroke, ALS, autism, Alzheimer’s, and AIDS. The parthenote stem cell studies can only be supported by non-federal funds, so to avoid conflict with federal agencies, the testis-derived stem cell research must also be non-federally funded. Adequate funding is the only unmet need to move this work forward. Your support is urgently needed.

Your contribution may benefit everyone you know

Ann A Kiessling, PhD
Director, Bedford Research Foundation

Who is Bedford Research Foundation?

Philanthropy Is The Key To Continued Progress

The average cost of each experiment is $90,000. Because much of our overhead is covered by fee-for-service laboratory tests, 92% of every dollar donated goes directly toward these experiments. This innovative funding model allows Bedford Research scientists greater flexibility to move quickly in promising new research directions.

Continued progress requires meeting our annual funding goal of $450,000 in 2019.

Donate Today!

 

Dr. Ann A. Kiessling honored with the Jacob Heskel Gabbay Award for Biotechnology and Medicine

Bedford Research Foundation

 

Dr. Ann A. Kiessling
Photo by Blake Gardner (hi-res jpg)

This is the twelfth year this award has been presented and the first year it has been awarded to a female scientist. This year, the award recognizes significant contributions to the field of assisted human reproduction. This international honor reflects Dr. Kiessling’s leading position in stem cell research and reproductive technologies.

Dr. Kiessling’s ground breaking Special Program of Assisted Reproduction (SPAR) allows HIV positive men to safely father children. The program’s success has been due to a revolutionary methodology developed to test semen for HIV, and a patented process for safely transporting specimens throughout the world by mail.

As of October, 2009, 101 healthy babies have been born from SPAR – a shining example of this pioneering science in action. This methodology helped solve a problem for families previously overlooked by the reproductive medicine community.

Dr. Kiessling’s work has also helped bridged a gap between assisted reproduction and basic research in stem cells. Using the micro-array technologies of previous Gabbay Awardees, Patrick O. Brown and Stephen P. A. Fodor, she is revealing the cellular machinery that gives rise to human embryonic stem cells. Understanding of this cell cycle regulation is urgently needed. It will revolutionize outcomes in assisted reproduction, the derivation of stem cells and our understanding of cancer.

Dr. Kiessling will present a talk entitled, “Retroviruses, Reproduction and Regenerative Medicine” on Monday, November 16 at 3:45 PM on Brandeis University campus in Gerstenzang Hall #123, admission is free. The award ceremony will be at 6 PM. tickets required.

 

BSCRF awards Representative Daniel E. Bosley with a Certificate of Appreciation

For Immediate Release:

Daniel Bosley and Ann KiesslingThe Bedford Stem Cell Research Foundation awards Representative Daniel E. Bosley (1st Berkshire) with a Certificate of Appreciation at the Activated Egg Symposium 2009.

The Foundation honored Representative Daniel E. Bosley in recognition of his dedication and tireless efforts on behalf of Stem Cell Science and Regenerative Medicine in Massachusetts.

“Representative Bosley was instrumental to the passage of the Massachusetts Stem Cell Bill in 2005. And we thank him for taking a leadership position in educating his fellow legislators about the importance of stem cell science,” said Dr. Ann Kiessling, director of the Bedford Stem Research Foundation as she presented the award.

Read More

Stem Cell scientists from major universities meet for a small, focused conference in Weston, Massach

Discussions will include estimates of time to develop new stem cell based therapies for degenerative diseases, including diabetes, Parkinson’s disease, spinal cord diseases, AIDS and heart failure.

At this crucial time, when the federal government is not funding any new human embryonic stem cell grants while federal guidelines are being organized, the Bedford Stem Cell Research Foundation’s Seventh Annual Activated Egg Symposium is bringing together an elite group of speakers from Connecticut, Massachusetts and California to share their latest research with other scientists, mostly funded by state stem cell research initiatives.

This year’s keynote, Renee A. Reijo Pera, director of Stanford’s Center for Human Embryonic Stem Cell Research and Education was interviewed last year in the New York Times for her controversial research using embryonic stem cells to create sperm and eggs. She will be joined by internationally known leaders including, Dr. Gary Stein, director of Massachusetts’ new International Stem Cell RegistryDr. Haifan Lin, director of the Yale Stem Cell CenterDr. Laura Grabel, Wesleyan University, Dr. Ann Kiessling, director of the Bedford Stem Cell Research Foundation, Dr. Ren-He Xu, director of the University of Connecticut-Wesleyan Stem Cell CoreDr. Jesse Mager, University of Massachusetts, Amherst, and I. Glenn Cohen, Harvard Law School’s new Petri Flom Center for Health Law Policy, Biotechnology and Bioethics. With attendance limited to 100, the event provides a unique environment for investigators from academia, industry and infertility clinics to meet, discuss their most recent science and form new collaborations.

Special guests this year also include, Senator Jack Hart and Representative Daniel E. Bosley, legislators behind Massachusetts’s stem cell bill passed in 2005.

Bedford Stem Cell Research Foundation is Massachusetts’ only independent, non-profit, – stem cell laboratory, currently located in Somerville, MA.

 

Stem Cell scientists from major universities attend a conference of 100-scientists and invited guest

Bedford Stem Cell Research Foundation

 

 

For Immediate Release:

Friday, Nov 6, 2009: Stem Cell scientists from major universities attend a conference of 100-scientists and invited guest in Weston, Massachusetts. Discussions will include estimates of time to develop new stem cell based therapies for degenerative diseases, including diabetes, Parkinson’s disease, spinal cord diseases, AIDS and heart failure.

At this crucial time, when the federal government is not funding any new human embryonic stem cell grants while federal guidelines are being organized, the Bedford Stem Cell Research Foundation’s Seventh Annual Activated Egg Symposium (http://www.bedfordresearch.org/symposium) is bringing together an elite group of speakers from Connecticut, Massachusetts and California to share their latest research with other scientists, mostly funded by state stem cell research initiatives.

This year’s keynote, Renee A. Reijo Pera, director of Stanford’s Center for Human Embryonic Stem Cell Research and Education was interviewed last year in the New York Times for her controversial research using embryonic stem cells to create sperm and eggs. She will be joined by internationally known leaders including, Dr. Gary Stein, director of Massachusetts’ new International Stem Cell Registry, Dr. Haifan Lin, director of the Yale Stem Cell Center, Dr. Laura Grabel, Wesleyan University, Dr. Ann Kiessling, director of the Bedford Stem Cell Research Foundation, Dr. Ren-He Xu, director of the University of Connecticut-Wesleyan Stem Cell Core, Dr. Jesse Mager, University of Massachusetts, Amherst, and I Glenn Cohen, Harvard Law School’s new Petri Flom Center for Health Law Policy, Biotechnology and Bioethics. With attendance limited to 100, the event provides a unique environment for investigators from academia, industry and infertility clinics to meet, discuss their most recent science and form new collaborations.

Special guests this year also include, Senator Jack Hart and Representative Daniel E. Bosley, legislators behind Massachusett’s stem cell bill passed in 2005.

Bedford Stem Cell Research Foundation is Massachusetts’ only independent, non-profit, – stem cell laboratory, currently located in Somerville, MA.  http://www.bedfordresearch.org.

For further information, contact:  (310-480-1234) or (781-718-7894).

 

 

Leading experts in basic science and clinical care discuss barriers

Shepherd Center

 

 

From Bench to Bedside:

Leading experts in basic science and clinical care discuss barriers to a “cure” for spinal cord injury. 

By Amanda Crowe, MA, mPH

It’s an exciting time for neuroscience, including the hope for new therapies to treat spinal cord injury (SCI). While basic scientists and clinicians are making important advances, they face daunting challenges when it comes to moving promising research from the bench to the bedside.

To identify and address these barriers, leading experts in neuroscience and stem cells recently came together for the one-day workshop at the University of Georgia.

“The concept of this workshop grew out of a need for better communication between stem cells scientists, who dared to use the term ‘cure’ for spinal cord injury, and care providers, who are worried about raising ‘false hopes’ and setting unrealistic goals for people with spinal cord injury,”says Ann Kiessling, Ph.D.,

associate professor of surgery at Harvard Medical School and director of the Bedford Stem Cell Research Foundation, which organized the second annual gathering in cooperation with Shepherd Center. “Both groups clearly have the patient’s best interest at heart, but were not hearing each other’s concerns.”

A key challenge for people with SCI is the concern among clinicians that any direct intervention at the site of the injury could impose further damage and additional loss of function, Dr. Kiessling says. “They are understandably reluctant to expose their patients to the risk of further spinal cord damage for research purposes,” she adds.

There is also a lack of infrastructure within the SCI research community to support multi-center studies, and to define how studies in SCI can be made safe and relevant to human patients. Keith Tansey, M.D., Ph.D., director of spinal cord injury research at Shepherd, spoke to the group about the need to ensure animal studies are more relevant to humans.

“Humans aren’t necessarily just big rats, and we need to better understand how and why animals are recovering from SCI because the mechanisms may not be the same in humans,” Dr. Tansey says. “Studies of animals and humans with incomplete injuries reveal a bias toward spinal plasticity in animals and brain plasticity in humans as the reason for functional recovery, so treatments may need to be different. In complete injuries, spinal circuits in rodents can regain stepping, but humans can’t, so we need to learn how to make human spinal cords function like rats’.”

Dr. Kiessling agrees, adding that animal model research needs to be more carefully aligned with human injuries and the out come goals for human therapies. “If walking is the outcome measure, animal models need to reflect that. But if bladder control is what’s important, a different animal model may be needed,” she says.

Researchers and clinicians must gain a better understanding of how much recovery is due to re-establishment of brainspinal cord connections versus improvements in interpreting and using sensory information in the spinal cord below the level of injury. Dr. Tansey challenged the traditional view of translational research in which discoveries at the cellular level move from the lab to clinical practice, arguing that it should be more of a two-way street. That is, questions that arise in the clinical setting can go back to the lab to find answers. Other attendees said this model could help inspire greater communication and partnership, as well.

A memorable highlight of the workshop was a tour of Shepherd Center, the only specialty rehabilitation center in the country that combines intensive medical care, rehabilitation and a clinical research program under one roof. This visit gave basic scientists a chance to see what their work can do at the human level, well beyond studying cell biology in the lab.

“We could have held this workshop anywhere in the country, but we were impressed by the clear enthusiasm and determination of Shepherd’s leadership, particularly Alana Shepherd, in creating a unique center of excellence in patient care,” Dr. Kiessling says.

Still, experts say the complexity of SCI cannot be overstated, and there is no silver bullet – no single cell, no single surgery, no single nerve-growth factor that will solve the whole riddle. “The more realistic expectation is that a combination of incremental steps is needed to improve recovery and maximize function,” Dr. Tansey says. “There is huge potential with stem cell biology and cell-replacement therapies, but there’s also a long distance between where we are today and where we need to be to find a ‘cure.’”

Collaborations among these leading experts will help forge the path forward. In the meantime, patients and their families should be encouraged by the progress made thus far, experts say. Prevention and early intervention, regeneration therapies at the cellular and extra-cellular levels and aggressive rehabilitation are all contributing to significant neurological recovery after SCI.

Professor I. Glenn Cohen Joins the Symposium Faculty

The Bedford Stem Cell Research Foundation is proud to announce that I. Glenn Cohen, JD will join the facutly as this year’s dinner speaker. Cohen is an assistant professor at Harvard Law School, and co-director of the Petri-Flom Center for Health Law Policy, Biotechnology and Bioethics.

Prof. Cohen is currently working on projects relating to reproductive technology and medical tourism, but his past work has included projects on end of life decision-making, FDA regulation, research ethics, and commodification. Prior to joining Harvard faculty, Prof. Cohen served as a clerk to Chief Judge Michael Boudin, U.S. Court of Appeals for the First Circuit.

2009 Activated Egg Symposium Speakers Posted

We are proud to post the 2009 line-up of speakers:

(Please see the full program here)

Dr. Laura Grabel
“From Embryonic Stem Cell to Neuron, with Stops Along the Way”

Dr. Ren He Xu
“A Neglected Role of bFGF in Supporting Culture of Human Pluripotent Stem Cells”

Dr. Haifan Lin
“Stem Cells, Small RNAs, and Self-Renewal of the Germline.”

Dr. Ann Kiessling
“Unique Cell Cycle Control in 8-Cell Human Embryos”

Dr. Jesse Mager
Essential functions of Yin-Yang1 during oogenesis and preimplantation development.”

Gary Stein, PhD
“Transcription Factor Mediated Epigenetic Control of Cell Growth Phenotype”