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Category: Stem Cell Research

ScienceDaily (May 14, 2010) — Deep inside the ear, specialized cells called hair cells detect vibrations in the air and translate them into sound. Ten years ago, Stefan Heller, PhD, professor of otolaryngology at the Stanford University School of Medicine, came up with the idea that if you could create these cells in the laboratory from stem cells, it would go a long way toward helping scientists understand the molecular basis of hearing in order to develop better treatments for deafness.

After years of lab work, researchers in Heller’s lab will report in the May 14 issue of Cell that they have found a way to develop mouse cells that look and act just like the animal’s inner-ear hair cells — the linchpin to our sense of hearing and balance — in a petri dish.

If they can further perfect the recipe to generate hair cells in the millions, it could lead to significant scientific and clinical advances along the path to curing deafness in the future, they said.

“This gives us real hope that there might be some kind of therapy for regenerating hair cells,” said David Corey, PhD, professor of neurobiology at Harvard University who was not involved in the study. “It could take a decade or more, but it’s a possibility.”

Using both embryonic stem cells from mice as well as reprogrammed mouse fibroblasts (a type of relatively undifferentiated cell found in many parts of the body), the researchers present a step-by-step guide on how to coax these cells into the sensory cells that normally reside in the inner ear.

“We knew it was really working when we saw them in the electron microscope,” Heller said. “They really looked like they were more or less taken out of the ear.”

Humans are born with 30,000 cochlear and vestibular hair cells per ear. (By contrast, one retina harbors about 120 million photoreceptors.) When a significant number of these cells are lost or damaged, hearing loss occurs. The major reason for hearing loss and certain balance disorders is that — unlike other species such as birds — humans and other mammals are unable to spontaneously regenerate these hearing cells.

As the population has aged and noise pollution has grown more severe, health experts now estimate that one in three adults over the age of 65 has developed a handicapping hearing loss due to the destruction of these limited number of hair cells.

One of the roadblocks to understanding the molecular basis of hearing is the paucity of hair cells available for study, Heller said. While researchers will ultimately need human hair cells, the mouse version is a good model for the initial phases of experimentation, he said. In addition to using mouse embryonic stem cells, the researchers used fibroblasts that had been reprogrammed to behave like stem cells: These are known as induced pluripotent stem cells, or iPS cells.

“Our study offers a protocol to generate millions of functional hair cells from a renewable source,” Heller said. “We can now generate these cells and don’t have to go through dozens of mice for a single experiment. This allows us to do molecular studies with much higher efficiency.”

The study details how the researchers succeeded in coaxing the mouse embryonic stem cells and the iPS cells through different phases of development that occur in the womb. According to lead author Kazuo Oshima, MD, PhD, a research instructor at Stanford who works in Heller’s lab, they started by turning the stem and iPS cells into the type of cells that form a young embryo’s ectoderm — the embryo’s outer layer of cells that eventually differentiate into many tissues and structures, such as skin and nerve cells. Next they used specific growth factors to transform them into “otic-progenitor” cells (otic means ear). And after that, they varied the chemical soup in the dish, so that the cells clustered in a manner similar to hair cells and developed stereociliary bundles, which are also characteristic of hair cells.

“We looked at how the ear develops in an embryo, at the developmental steps, and mimicked these steps in a culture dish,” Heller said.

Hair cells in the inner ear contain tiny clumps of hair-like projections, known as stereocilia. Sound vibrations cause the stereocilia to bend slightly, causing mechanical vibrations that are then converted into an electrochemical signal that the brain interprets as sound.

The cells in the petri dish, under close examination, had this same structure.

“These cells have a very intriguing structure,” Heller said. “They look like they have hair tufts of stereocilia.”

More importantly, further study showed that the cells also responded to mechanical stimulation by producing currents just like hair cells. Using a probe, researchers stimulated the bundles and recorded the currents that were evoked. Co-author Anthony Ricci, PhD, associate professor of otolaryngology, was responsible for this step of the work.

Heller, a leader in stem-cell based research on the inner ear, has recently been focused on two paths for possible cures for deafness: drug therapy — which could be as simple as an application of ear drops — and stem cell transplantation into the inner ear.

Both paths could be further advanced by the ability to develop hair-cell-like cells, he said. “We could now test thousands of drugs in a culture dish,” he explained. “It is impossible to achieve such a scale in animals. Within a decade or so we could reap the benefits of this type of screening.”

The lab’s research into the regeneration of hair cells for transplantation into the inner ear to cure deafness will also continue.

“We made hair-cell-like cells in a petri dish,” said Oshima. “This is an important step toward development of future therapies.”

The study was funded by grants from the National Institute of Health, the California Institute for Regenerative Medicine and by a Neuroscience of Brain Disorders Award from the McKnight Endowment Fund for Neuroscience.

Other Stanford co-authors include postdoctoral scholars Kunyoo Shin, PhD; Mark Diensthuber, MD; and Anthony Peng, PhD.

The news that stem cell transplants into sufferer of Type 1 diabetes have allowed patients to forego their traditional daily insulin injections has come following research that allowed volunteers to successfully go an average of two-and-a-half years free from needing to take their multiple, daily injections with which they usually manage their condition thanks to stem cell therapy. The small study that was undertaken included 23 patients that had been recently diagnosed with type 1 diabetes. Type 1 diabetes is a condition where a person’s immune system can very quickly destroy the cells that produce insulin found in the pancreas.

The stem cell transplants appear to work by effectively re-setting the immune system on order that the body will cease attacking the pancreas. According to the researchers involved in the study such a treatment can only successfully be undertaken when Type 1 diabetes is caught early in a patient, preferably within a six week window following diagnosis and before the pancreas suffers irreparable damage and before any complications set in as a result of elevated blood sugar levels.

With regards to the study itself 23 patients received stem cell treatments in order to treat new-onset cases of type 1 diabetes, making use of follow-up data from 15 patients that initially received stem cell implants in a study previously published in 2007 combined with another eight patients that joined the study all the way up until April 2008. The patients involved in the study were aged between 13 and 31 years old with an average age of just over 18. The majority of the patients were men who had suffered for a relatively short duration from the disease before it was caught (around 37 days on average) and were, in general, free of diabetic ketoacidosis – a condition that is dangerous complication linked to Type 1 diabetes.

The new study has hinted at possible new avenues for research, although it must be stressed that the treatment is still at an early stage of its development and it is not without certain risks and side effects. In fact the research director of Diabetes UK, Dr Iain Frame, has been quick to stress that “This treatment is not a cure for type 1 diabetes.”

The researchers obtained follow-up data on all of the 23 patients that were in receipt of a stem cell therapy transplant and the length of their data collation for each patient ranged from seven to fifty-eight months. Their findings showed that 20 patients, all with no previous ketoacidosis, became insulin and injection free, and of all involved a total of twelve patients stayed insulin-free for an average of thirty-one months. Eight patients, however, suffered relapses and needed to resume taking insulin at low doses.

While the results from this study indicate that further research definitely needs to be done into the process as well as highlights the fact that there will undoubtedly need to be further work done among people of different ethnicities and among women in order to further test the findings of the study it nevertheless shows promise for many Type 1 diabetes sufferers.

NEW YORK (March 4, 2010) — In a leap toward making stem cell therapy widely
available, researchers at the Ansary Stem Cell Institute at Weill Cornell
Medical College have discovered that endothelial cells, the most basic building
blocks of the vascular system, produce growth factors that can grow copious
amounts of adult stem cells and their progeny over the course of weeks. Until
now, adult stem cell cultures would die within four or five days despite best
efforts to grow them.

“This is groundbreaking research with potential application for regeneration of
organs and inhibition of cancer cell growth,” said Dr. Antonio M. Gotto Jr., the
Stephen and Suzanne Weiss Dean of Weill Cornell Medical College and Provost for
Medical Affairs of Cornell University. “We are indebted to Shahla and Hushang
Ansary for founding this Institute and to the Starr Foundation Tri-Institutional
Stem Cell Initiative for ongoing support.”

This new finding sets forth the innovative concept that blood vessels are not
just passive conduits for delivery of oxygen and nutrients, but are also
programmed to maintain and proliferate stem cells and their mature forms in
adult organs. Using a novel approach to harness the potential of endothelial
cells by “co-culturing” them with stem cells, the researchers discovered the
means to manufacture an unlimited supply of blood-related stem cells that may
eventually ensure that anyone who needs a bone marrow transplant can get one.

The vascular-cell model established in this study could also be used to grow
abundant functional stem cells from other organs such as the brain, heart, skin
and lungs. An article detailing these findings appears in the March 5 issue of
the journal Cell Stem Cell.

In adult organs, there are few naturally occurring stem cells, so using them for
organ regeneration is impractical. Until now, strategies to expand cultures of
adult stem cells, which invariably used animal-based growth factors, serum, and
genetically manipulated feeder cells, have only been marginally successful. This
study, which employs endothelial cells to propagate stem cells without added
growth factors and serum, will likely revolutionize the use of adult stem cells
for organ regeneration, as well as decipher the complex physiology of the adult
stem cells.

“This study will have a major impact on the treatment of any blood-related
disorder that requires a stem cell transplant,” says the study’s senior author,
Dr. Shahin Rafii, the Arthur B. Belfer Professor in Genetic Medicine,
co-director of the Ansary Stem Cell Institute and a Howard Hughes Medical
Institute Investigator, at Weill Cornell Medical College. Currently, stem cells
derived from bone marrow or umbilical cord blood are used to treat patients who
require bone marrow transplants. Most stem cell transplants are successful, but
because of the shortage of genetically matched bone marrow and umbilical cord
blood cells, many patients cannot benefit from the procedure.

“Over the last few decades, substantial funding has been spent to develop
platforms to expand adult stem cell cultures, but these efforts have never been
able to coax an authentic adult stem cell to self-renew beyond a few days,”
continues Dr. Rafii. “Most stem cells, even in the presence of multiple growth
factors, serum, and support from generic non-endothelial stromal cells, die
after a few days. Now, employing our endothelial stem cell co-cultures, we can
propagate bona fide adult stem cells in the absence of external factors and
serum beyond 21 days with an expansion index of more than 400-fold.”

If this vascular-based stem cell expansion strategy continues to be validated,
physicians could use any source of hematopoietic (blood-producing) stem cells,
propagate them exponentially, and bank the cells for transplantation into
patients.

In a true first, the study demonstrates how this novel vascular cell platform or
“vascular niche” can self-renew adult hematopoietic stem cells for weeks, both
in vitro and in vivo, by co-culturing them on a bed of endothelial cells. The
researchers chose endothelial cells because they are in close contact with blood
stem cells, and previous work from Dr. Rafii’s lab had demonstrated that
endothelial cells produce novel stem-cell-active growth factors. However,
maintenance of the endothelial cells is cumbersome and if they are not “fed”
specific substances, such as growth factors known as “angiogenic factors,” they
immediately die. To get around this problem, the researchers genetically
engineered the endothelial cells to stay in a long-term survival state by
inserting a recently discovered gene cloned from adenoviruses, which does not
promote oncogenic transformation of the human cells. This earlier discovery,
using a single gene to put endothelial cells into a long-lasting “suspended
animation” state without harming their ability to produce blood vessels, was
also discovered in Dr. Rafii’s lab and published in the journal Proceedings of
National Academy Sciences in 2008.

Endothelial Cells Could Generate Stem Cells and Their Differentiated Progeny
In this study, the researchers also discovered that endothelial cells not only
could expand stem cells, but also instruct stem cells to generate mature
differentiated progeny that could form immune cells, platelets, and red and
white blood cells, all of which constitute functioning blood.

“We are the first group to demonstrate that endothelial cells elaborate a
repertoire of stem-cell-active growth factors that not only stimulate stem cell
expansion but also orchestrate differentiation of these stem cells into their
mature progeny,” says Dr. Jason Butler, a senior investigator at Weill Cornell
Medical College and first author of the study. “For example, we have found that
expression of specific stem-cell-active factors, namely Notch-ligands, by the
endothelial cells lining the wall of working blood vessels promote proliferation
of the blood-forming stem cells. Inhibition of these specific factors on the
endothelial cells resulted in the failure of the regeneration of the
blood-forming stem cells. These findings suggest that endothelial cells
directly, through expression of stem-cell-active cytokines, promote stem cell
reconstitution.”

Further describing this innovative concept, in a high-impact article published
in the January 2010 issue of Nature Reviews Cancer, Drs. Rafii and Butler, and
Dr. Hideki Kobayashi, who is also a co-author of the current study, have
elaborated on specific endothelial cell-produced growth factors that promote the
growth of tumor cells besides stem cells.

Development of the vascular-cell technology that supports long-lasting growth of
stem cells will also allow scientists to generate abundant sources of functional
and malignant stem cells for genetic and basic studies. This study has also
resolved a long-standing controversy in which several groups had claimed that
bone-forming cells (osteoblasts) exclusively support the expansion of
blood-forming stem cells. “However, using a highly sophisticated molecular
imaging approach, we show that regenerating blood-forming stem cells in the bone
marrow are in intimate contact with the blood vessels, indicating that
endothelial cells are the predominant regulator of stem cell repopulation in the
adult bone marrow,” states Dr. Daniel Nolan, a senior scientist in Dr. Rafii’s
lab and a co-author of the new study.

One other important concern addressed in this study was whether forced expansion
of the stem cells over a long period of time would induce cancerous mutations in
the stem cells. However, the authors of this study show that, even after one
year, there was no indication of tumor formation, such as leukemias, when the
expanded stem cells were transplanted back into mice. This suggests that the
endothelial cells provide a milieu that proliferates stem cells without creating
cancer risk.

Dr. Rosenwaks says, “Generation of endothelial cells derived from diseased
embryonic stem cells that are being propagated in our Derivation Unit will open
up new avenues of research to molecularly eavesdrop on the communication between
vascular cells and stem cells. This innovative line of investigation to
determine how normal and abnormal human vascular cells induce the formation of
organs during development of embryos and how dysfunction of endothelial cells
results in developmental defects will lay the foundation for novel platforms
for therapeutic organ regeneration.”

Dr. Rafii sees even more opportunities. “Identification of as yet unrecognized
growth factors produced by human embryonic cell-derived endothelium and adult
endothelial cells that support stem cell expansion and differentiation will
establish a new arena in stem cell biology. We will be able to selectively
activate endothelial cells not only to induce organ regeneration, but also to
inhibit specifically the production of endothelial cell-derived factors in order
to block the growth of tumors. Our findings are the first steps toward such
goals and they highlight the potential of vascular cells for generating
sufficient stem cells for therapeutic organ regeneration, tumor targeting, and
gene therapy applications,” concludes Dr. Rafii.

For more information, visit www.med.cornell.edu.

March 2, 2010 – Houston – A heart patient’s own skin cells soon could be used to
repair damaged cardiac tissue thanks to pioneering stem cell research of the
University of Houston’s newest biomedical scientist, Robert Schwartz.

His new technique for reprogramming human skin cells puts him at the forefront
of a revolution in medicine that could one day lead to treatments for
Alzheimer’s, diabetes, muscular dystrophy and many other diseases.

Schwartz brings his ground-breaking research to UH as the Cullen Distinguished
Professor of Biology and Biochemistry and head of UH’s new Center for Gene
Regulation and Molecular Therapeutics. He also is affiliated with the Texas
Heart Institute at St. Luke’s Episcopal Hospital in the Texas Medical Center,
where he is director of stem cell engineering.

“Professor Schwartz’s work will save lives, and his decision to pursue this
pioneering research at UH is a big leap forward on our way to Tier-One status,”
said John Bear, dean of the UH College of Natural Sciences and Mathematics.
“Together with the many other outstanding scientists we’ve assembled here,
Schwartz will help make this university a major player in medical research.”

Schwartz devised a method for turning ordinary human skin cells into heart
cells. The cells developed are similar to embryonic stem cells and ultimately
can be made into early-stage heart cells derived from a patient’s own skin.
These then could be implanted and grown into fully developed beating heart
cells, reversing the damage caused by previous heart attacks. These new cells
would replace the damaged cardiac tissue that weakens the heart’s ability to
pump, develops into scar tissue and causes arrhythmias. Early clinical trials
using these reprogrammed cells on actual heart patients could begin within one
or two years.

Although Schwartz is not the first scientist to turn adult cells into such stem
cells, his improved method could pave the way for breakthroughs in other
diseases. Schwartz’s method requires fewer steps and yields more stem cells.
Armed with an effective way to make induced stem cells from a patient’s own
skin, scientists can then begin the work of growing all kinds of human cells.

For example, new brain cells could treat Alzheimer’s patients or those with
severe brain trauma, or a diabetic could get new insulin-producing cells in the
pancreas. Generating new kidney, lung or liver tissue is also possible, with
scientists even being able to one day grow an entirely new heart or other organ
from these reprogrammed cells. Additionally, Schwartz and his team are working
on turning induced stem cells into skeletal muscle cells to treat muscular
dystrophy.

“We’re trying to advance science in ways folks never even dreamed about,”
Schwartz said. “The idea of having your own bag of stem cells that you can
carry through life and use for tissue regeneration is at the very cutting edge
of science.”

This latest biomedical hire is a major step in the UH Health Initiative, an
effort aimed at having the university become a world-class center for medical
research. Creating new cross-disciplinary academic and health-related research
opportunities for faculty and students is crucial to this initiative, as are
collaborations with other Texas Medical Center member institutions. One of its
top goals is to increase the amount of sponsored research expenditures awarded
to UH, which is a key factor in attaining Tier-One status.

“Dr. Schwartz will expand UH’s expertise in promising new areas of scientific
discovery to alleviate human disease. By recruiting premier scientists like
Schwartz, UH is fast becoming a major player in the regional biomedical research
community,” said Kathryn Peek, assistant vice president of University Health
Initiatives at UH.

Schwartz has decades of experience at the Texas Medical Center. Before coming
to UH, he was director of the Institute of Biosciences and Technology, a
research component of the Texas A&M Health Science Center. He also was a
longtime tenured professor at Baylor College of Medicine and co-directed the
school’s Center for Cardiovascular Development. The new research center
Schwartz heads at UH will be housed in state-of-the-art laboratory facilities at
the university’s Science and Engineering Research Center.

What attracted him to UH was the commitment of administrators and faculty to
making the university a premier center for biomedical research. His hiring
comes just a year after the arrival of Jan-Åke Gustafsson, a world-renowned
scientist and cancer researcher. They join other leading UH faculty, ranging
from biochemists to computer scientists and mathematicians, who are deeply
involved in cutting-edge medical research.

Embryonic stem cell research has gained a huge momentum these days because of its? potential to cure deadly diseases like Alzheimer?s, Parkinson, type 1 diabetes, spinal cord injuries, stroke, bone diseases, multiple sclerosis, cancer and much more! However many people argue that the embryonic stem cell research is not ethical and therefore, should be stopped. Even though this debate continues to grow, we simply cannot undermine the immense potential which this research holds!

Let me tell, you something about Embryonic stem cells. Basically, embryonic stem cells are stem cells that have been derived from the inner cell mass of an early stage embryo, also known as blastocyst, which forms after 4-5 days post fertilization. These cells are considered special because they have the ability to differentiate into organized tissue, organs or cells of the body. This means that the embryonic stem cells have the capability to give rise to different organs or tissues of an organism such as liver, brain, kidney etc.

Since these cells are plutripotent, so they can be used to replace or treat a malfunctioning or dying organism. Apart from treating deadly diseases, embryonic stem cells are also being used for understanding the process of aging and helping the scientists to find out about the enzymes involved in the process of aging. By blocking these enzymes, we can certainly slower the phenomenon of aging.
The stem cells and umbilical cord cells have also been used for treating leukemia and lymphoma patients. So, you can see that stem cells have a lot of potential in making the world free of diseases!

However, the opponents do not favor this research on ethical grounds. It is because the embryonic stem cells are taken or derived from early stage embryos- which is regarded as the death of life! The pro-life and religious groups say that an embryo represents human life and if the embryonic stem cells are taken out, then it is equivalent to murdering a human life. The religious groups also point out that many fetuses and embryos are being aborted because of this on-going research. Currently, there are several sources of embryos, including unwanted embryos and fertility clinics- which have hundreds of frozen embryos. It has been said that it is against the ethical laws to kill any innocent human being intentionally- even if it benefits the entire human community!

Well, these are some of the points in favor of and against the stem cell research Stem cell research is really beneficial and it is important that we focus on the benefits rather than considering the negatives!

Before going further into the article, let me give you some information about stem cells. Stem cells are found in all multi-cellular organisms and are categorized as undifferentiated cells-meaning that they have the potential to develop into various specialized cells in the body during early development of an organism. Stem cells have the capacity to differentiate into specialized cells/organs such as kidney, liver, lungs, heart etc- and hence are of primary importance to human beings.

Stem cells have two special properties- firstly; they are unspecialized cells, having the ability to renew themselves through cell division and secondly, under certain experimental conditions they can be induced to become tissue or organ specific cells with specialized functions. Stem cells are basically of two types- embryonic stem cells or adult stem cells. The embryonic stem cells are derived from the early morula stage embryos or the inner cell mass of the blastocyst. On the other hand, the adult stem cells are undifferentiated stem cells that are found among differentiated tissues/organs and multiply be cell division to repair/renew the tissues in which they are
present.

Adult Stem cells are found in various organs such as brain, bone marrow, peripheral blood, blood vessels, heart, gut, skin, teeth, skeletal muscle, liver etc. The research on adult stem cells has aggravated lots of excitement and debate amongst the scientists all over the world. Scientists have found out that lots of adult stem cells are present in structured tissues and organs- which is an indication of the fact that these cells can be used for transplants or can be induced to grow into specialized cells. However, one of the major drawbacks in using adult stem cells is that they are often restricted to certain types of lineages-meaning that the adult stem cell of a particular lineage will not be able to divide into different type of lineage!

In spite of the above drawback, the adult stem cells have been used for several years for successfully treating leukemia and related bone/blood cancers. The use of adult stem cells has not been considered controversial so far because unlike the embryonic stem cells (which are derived from the embryo), they are derived form the adult organs-and it does not require the destruction of the embryo.

The first successful example of using adult stem cells for transplant was carried by Paolo Macchiarini, at the Hospital Clinic of Barcelona, on a Columbian adult female whose trachea had been distorted due to tuberculosis. The entire procedure of carrying out the transplant occurred normally and the tissue exhibited no signs of rejection, even after months of transplant.

Adult stem cells are very valuable and a lot of research is still going on to find out the other applications or uses of these cells. Adult stem cells have numerous potential and if the information is decoded wisely, then soon we will have a world free of diseases!