The Bedford Research Foundation (BRF), a Massachusetts not-for-profit organization conducting stem cell research for diseases currently considered chronic or incurable, has moved it’s research and laboratory facility to Bedford Massachusetts after being located in Somerville for over 15 years.
Bedford Research Foundation supports ground breaking work with fellowship money
As the result of a generous benefactor, the Bedford Research Foundation has placed a fellow in Spain who is contributing significantly to understanding cellular programming and pluripotency in Stem Cells.
Dr. Sebastian Canovas is a Principal Investigator researcher from the Program for Cell Therapy and Regenerative Medicine of Andalucia, Foundation “Progreso y Salud”, in Seville, Spain. Dr Canovas received his DVM in 2002 from the University of Murcia (Spain) and in 2005 he completed his Master’s degree in Biotechnology of Reproduction in Mammals. During six years (2002-2008) he was working in the group Physiology of Reproduction in embryology, sperm functionality and sperm-oocyte interactions.
Following completion of his PhD, he joined Dr. Cibelli’s laboratory (Cellular Reprogramming Laboratory) at Michigan State University (USA) where his research had been focused on understanding the mechanisms of cellular reprogramming during embryo development and induced pluripotent stem cells production. To elucidate these mechanisms, Sebastian studied the role of a H3K27me3 histome demethylase (JMJD3) in bovine at early embryo development and during human make induced pluripotent stem cells process. Also, he has development a project for enhancing the efficiency in the production of safe iPS cells using episomal plasmids and adult somatic cells.
Now, his team is involved on a project to make transdifferentiation from human somatic cells forwards germinal cells. As a result of his work, he has published more than 12 scientific papers in journals with impact factor and he is collaborating in 6 research grants. Dr. Canovas hopes these studies will help lead to cures of rare disorders and fertility, which are affecting the population but they have not an effective treatment.
In 1996, the Bedford Research Foundation was formed in response to a need for specialized tests and services that were not available anywhere in the world. Today, we still provide these specialized tests and it has led us to a new model of funding:
“The Foundation is a forward thinking institution that covers overhead costs with fee-for-service testing, thus allowing philanthropic donations to go directly to research.”
Breakthroughs in understanding circadian rhythms in stem cells.
Fall 2014: Bedford Research scientists are following up on their discovery that stem cells have a circadian rhythm that may need to be supported for optimum development in the laboratory.
In the body, the daily pattern of light and dark controls many signals sent out by the brain, such as those that trigger changes in body temperature, and feelings of hunger and sleepiness.
Stem cells may especially need circadian signals to differentiate into specific cell types, such as neurons or bone marrow — but what type of signal should they receive in the laboratory? And what frequency? There is growing evidence that each type of cell needs a different circadian signal.
Following up Bedford’s discovery that stem cells may be controlled by circadian rhythms.
Bedford Research scientists discovered that stem cells may need circadian rhythm signals. This insight would make them analogous to several types of cells in the body, including some cancer cells. If true, new methods of cell culture need to be developed to enhance stem cell development. Bedford Research scientists isolated a new line of stem cells from a research mouse (Per2Luc) whose cells glow when one of the circadian genes is active (Figure 1). Efforts to study the new Per2Luc stem cells have been hindered by the lack of a sensitive photo-microscope to detect and record the glow — until very recently. An exciting, new photo-microscope (LV200) is sensitive enough to capture circadian oscillations in the Per2Luc cells (Figure 1). This advance will allow more rapid studies of the importance of circadian signals to stem cell expansion and differentiation.
Update June 15, 2014:Commencement Address a Success
Despite a prank from University of Oregon, Dr. Kiessling’s message about taking an active role in government hit home with the largest graduating class in OSU history. read more…
Update June 18, 2014:Pilot of the “Go Ducks” Plane to Donate $500 to Bedford Research
“We knew that the “Go Ducks !” message would be controversial, but we never imagined the depth of the offense our error in judgment has caused.” read more…
Cytomegalovirus (CMV) is more common in semen than generally thought, according to a new study by Bedford Research Foundation scientists.
CMV is a common herpes virus that causes a minor disease in children and adults, but can also infect fetuses in utero and causes permanent problems in 1 out of 750 children born in the U.S.
In the February issue of Fertility and Sterility, the official journal of the American Society for Reproductive Medicine (ASRM), Bedford Research scientists report two surprising findings: First, nearly half (45%) of the semen specimens from 68 men without and with HIV co-infection had detectable CMV, including specimens from two men who initially tested negative for antibody against CMV in their blood. Second, men with even mild suppression of their immune system were twice as likely (57%) to have CMV in their semen as men with normal immunity (28%).
Stem cell-based treatments, termed regenerative medicine, are being developed to replace defective tissues and organs such as heart and kidney failure, spinal cord injury and disease, diabetes, AIDS, Parkinson’s and Alzheimer’s diseases, and degenerative joints. The source of the stem cells is key. If they can be harvested from the patient, there will be no problems with tissue rejection, such as can happen with kidney or heart or bone marrow transplants from donors. SCNT provides a powerful method to create stem cells with the patient’s own chromosomes, thus a perfect tissue match. SCNT had been accomplished in many species, but not human.
The human egg is a huge cell, that is released from the ovary surrounded by cells that support it. The blue areas shown above are the DNA, the genetic information contained within each cell. The cluster of blue within the egg is the egg’s chromosomes, half of which will be expelled when the sperm enters, so the developing embryo will have genetic information from both the mother and the father.For parthenogenesis, the egg chromosomes alone guide development, for SCNT, the chromosomes are usually removed with a tiny pipette so the only genetic information remaining is from the transferred nucleus.
Background to SCNT
SCNT was first performed several decades ago to test whether or not every cell in the body contains all the genetic information of the individual. For example, does a liver cell contain all the genetic information to form every other type of cell, but “non-liver” genes are silenced? Or does a liver cell lose other genes and only retain “liver” genes?
Dr. John Gordon received the Nobel Prize in 2012 for demonstrating in 1958 that tadpole cell nuclei contained all the chromosomes necessary to form new frogs following transfer into frog eggs whose own chromosomes had been removed. The new frogs were genetically identical to the tadpole. Frogs were the first cloned animals.
For nearly three decades, it was believed that although successful with amphibia, mammals could not be cloned by transferring a nucleus into an egg, although other types of studies had confirmed that all cells contain all the genetic information needed to form a new being.
In 1997, to the surprise of the scientific community, Dolly the sheep was cloned by SCNT into a sheep egg, thus proving that like frogs, mammals could also be cloned from a single cell (Ian Wilmut at the Activated Egg Symposium (video)). Since then, many species have been similarly cloned, including mice, rats, rabbits, dogs, goats and cattle.
What is the magic contained within an egg?
Perhaps partly because of its enormous size, an egg has a unique capacity to remodel the structure of chromosomes, including its own and those of sperm. The remodeling allows expression of all the genetic information needed for stem cell pluripotency. Without being fertilized by sperm, eggs can be activated to generate stem cells, parthenote stem cells (1 min video about Parthenotes), using their own chromosomes. Parthenote stem cells have all the pluripotency characteristics of stem cells derived from human embryos (1 min video about hES). These studies suggested that SCNT would be highly successful in human eggs.
Why no human SCNT cells before now?
The inability to derive a line of stem cells from SCNT into human eggs has been a mystery, thought to be related to the status of the egg itself.
Thirteen years ago, Bedford Research scientists (JRM, 2001 (pdf)) reported side by side experiments activating human eggs parthenogenetically and by SCNT. Although 12 out of 22 parthenote eggs did divide and progress to the blastocyst stage, only 3 out of 19 SCNT eggs divided once or twice, and none progressed to the blastocyst stage (schematic). These results led to the current ongoing work by Bedford Research scientists to fully characterize gene expression in normal 8-Cell human embryos to begin to understand the problems with human parthenotes and SCNT eggs (JARG 2010; JARG 2009).
8-cell human embryo
A few years later, a large South Korean scientific team, well experienced in SCNT and animal cloning, reported the successful generation of several stem cell lines from SCNT into human eggs. The reports were quickly dispelled by other South Korean scientists as being totally fraudulent. This was a huge blow to the integrity of the stem cell scientific community.
Nonetheless, the lesson learned from the South Korean reports is that they had access to approximately 2,000 human eggs and had been unsuccessful in SCNT. This revealed loud and clear that there was a fundamental difference between human eggs and those of other mammals.
Two years ago, a New York scientific team headed up by Dieter Egli (AES 2011, Time 2011) reported deriving SCNT stem cells from human eggs whose chromosomes had not been removed (Nature, Vol 478). There was something helpful about leaving the human egg chromosomes in the egg during the activation process. This is regarded as an important breakthrough even though the resulting stem cells contain twice as many chromosomes as normal stem cells.
And now comes the Oregon scientific team reporting the successful derivation of SCNT stem cell lines by utilizing advances in egg culture, activation, and chromosome removal. Nonetheless, that unknown egg-specific factors play a role, however, was shown by marked differences in SCNT success rates.
Unfortunately, there are irregularities in the manuscript reported in Cell (Science Magazine, May 23, 2013), thus once again casting a shadow over the work. Other scientific teams are currently investigating the cell lines to determine the accuracy of the report.
Are SCNT eggs actually embryos?
Accuracy of language for new technologies involving human eggs will provide the balanced framework necessary for everyone to evaluate the value — and the threat — of SCNT technology (CT law review). If “embryo” is reserved for the unique union of egg and sperm, and if other activities of human eggs have more accurate terms, such as parthenote for eggs activated with their own chromosomes, and SCNT-egg (or “ovasome”) for eggs activated following SCNT, there will be far less confusion, especially by the non-scientific community.
Whether or not SCNT-eggs should be assigned the same status as embryos since there is the potential — however small — that such an entity could develop further if transferred into a uterus (“human cloning”) is a separate consideration from whether or not they should be termed “embryos.” New technologies need new terms.
The Bedford Stem Cell Research Foundation has announced that Dr. Ann Kiessling, its award-winning founder and executive director, is stepping down from the Harvard Medical School faculty after 27 years to devote her full attention to the stem cell research and other initiatives of the Foundation.
“My nearly three decades at Harvard have been wonderful, highly productive years for the two areas of NIH-funded research in my laboratory: reproductive biology of eggs and early embryos, and semen transmission of HIV. Being surrounded by highly talented HMS faculty, both clinical and basic science, stimulated our thinking and shortened the timeline to research answers,” said Dr. Kiessling, a nationally recognized pioneer in stem cell and HIV research.