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September 20, 2012 by
Inflammatory Bowel Disease Treatable With Stem Cells?
Researchers at Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine may have discovered the key to treating inflammatory bowel disease (IBD).
Dr. Graca Almeida-Porada and her team of scientists found a specific stem cell population in cord blood that migrates to the intestine and proliferates there.
Fetal sheep were injected with the stem cells and their intestines were analyzed 11 weeks later.
“These cells are involved in the formation of blood vessels and may prove to be a tool for improving the vessel abnormalities found in IBD,” said Dr. Almeida-Porada.
Intestinal swelling, inflammation and ulcers typically cause abdominal pain and diarrhea in IBD patients. Reducing inflammation is a key to treatment but currently approved drugs are not very effective.
“This study shows that the cells can migrate to and survive in a healthy intestine and have the potential to support vascular health,” said Almeida-Porada. “Our next step will be to determine whether the cells can survive in the ‘war’ environment of an inflamed intestine.”
September 14, 2012 by
Stem cell treatment in Panama benefits autistic Glenburn youth
As Kenny Kelley of Glenburn awaits an infusion of adult stem cells at a Panamanian city in November 2011, a Panamanian physician holds two syringes containing the cells. Autistic since birth, Kenny has undergone several such infusions since 2009.
By Dale McGarrigle, Of The Weekly Staff
Bangor Daily News
Posted Sept. 14, 2012, at 12:17 p.m.
GLENBURN — Now Kenny can read.
Kenny Kelley can now also do many things that other 11-year-olds take for granted. According to his mother, Marty Kelley, that’s because injections of adult stem cells, taken from umbilical cord blood, have helped Kenny to shake off the shackles of autism, with which he was first diagnosed at age 2.
“The results from stem cells can be seen everyday in his amazing thoughts and vast imagination!!,” Marty Kelley wrote in her blog, http://www.kensjourneytorecovery.blogspot.com/. “How lucky we are for such a miracle treatment!”
Autism is a brain disorder found in children that interferes with their ability to communicate and relate to other people. Autism affects 1 in 88 children and 1 in 54 boys. What causes autism has not been established.
Stem cells are the body’s internal repair system and can fix and replace damaged tissue. These unspecialized cells are a blank slate, capable of transforming into muscle cells, blood cells, and brain cells. Stem cells can also renew themselves by dividing and giving rise to more stem cells.
Stem cells taken from umbilical cord blood, such as Kenny received, are the least likely to be rejected.
The stem-cell treatment is the latest effort by Marty and her husband, Donald, to find ways to improve Kenny’s life. The Kelleys also have two other children: Philip, 13, and Caroline-Grace, 6.
First was in-home treatment in a mild hyperbaric oxygen chamber, three hours a day equaling 800 hours over the course of two years, beginning when Kenny was 5 ½ to 6 years old. This was coupled with a Specific Carbohydrate Diet, which restricts the use of complex carbohydrates and eliminates refined sugar and all grains and starch from the diet.
“We saw results right away with the chamber,” Marty recalled in a recent interview. “He made slow gains, such as tracing the alphabet.”
Then the Kelleys discovered on the Internet the story of Matthew Faiella, a New York boy who has been making great strides after stem-cell treatment in Panama for his autism. They decided to follow suit.
Why take this path, when there has been little scientific research into the use of stem cells to treat autism?
“We were willing to do it as long as it’s safe, and I’ve researched this,” Marty said. “Stem cells are very natural. I’m not a scientist, but I care much more than any scientist would, and I would never do anything to hurt my baby.”
When Kenny went for his first stem-cell treatment in July 2009, at the Stem Cell Institute in Costa Rica, Marty assessed the condition of her then 8-year-old son in her blog http://www.kensjourneytorecovery.blogspot.com:
• Behavior: Screaming, aggressive, giggles/silly/inappropriate with his brother or new people, running around, destructive, uncooperative while being dressed, hitting, not potty trained (still wearing diapers).
• Speech: Vocabulary of a 4-year-old. He can talk, but it is difficult for strangers to understand him. Answers some questions, but he does not understand or like why, when, or how questions.
• Physical: A body the size of a 5-year-old boy.
Kenny has had stem-cell treatments in 2009, 2010, and May and November of 2011. The repeated treatments are required because adult stems cells will work repairing cells for a period of time, about six months, then leave the body.
“When I think I’ve seen his skills level out, we’ll go for another treatment,” explained Marty.
What are some of the changes that Kenny has undergone in the past three years? First came the ability to read and clearer speech.
“When he got back, he just picked up a book and started reading, and I could understand every word,” said Mike Hughes, Marty’s brother. “It was like a light just turned on.”
Other gains: Kenny is talking about past events for the first time, and he’s conversational now. He expresses opinions and looking ahead to the future. He was finally potty trained at age 9. He’s doing math now. He’s calmed down considerably. This summer, he went to summer camp, staying overnight for three nights, in the same cabin as Philip.
“There’s no doubt in my mind how much he’s progressing,” Marty said. “We’re working on catching up right now, and how do we best do that?”
The costly treatment, which isn’t covered by insurance, hasn’t been approved yet by the Food and Drug Administration. Despite the fact that the stem cells come from the human body, the cells are considered a new drug by the FDA and are subject to stringent research and testing that can take years.
So this leaves the Kelleys and others like them seeking stem-cell treatment, going overseas to get it.
“It’s just a matter of how much are you going to spend,” Marty said. “There’s no treatment here that was going to do this much for him.”
August 10, 2012 by
Mesenchymal Stem Cells Stop Arthritis in its Tracks – Duke University
Researchers at Duke University announced a promising new stem cell therapy aimed at osteoarthritis prevention after a joint injury.
The probability of developing arthritis after injury (post-traumatic arthritis – PTA) greatly increases after injury. Currently, the US FDA has not approved any drugs that slow or eliminate the progression of PTA.
However, at Duke researchers are beginning to confirm mesenchmal stem cell (MSCs) therapy in arthritis treatment. The treatment is similar to that which professional athletes and others have been seeking abroad in places like Panama and Germany for the past few years.
Ref: Pro/Am Dancer is “Dancing with the Stars” Again After Stem Cell Therapy in Panama
In the study, mice sustaining fractures that commonly lead to arthritis were treated with MSCs. “The stem cells were able to prevent post-traumatic arthritis,” said Farshid Guilak, Ph.D., director of orthopaedic research at Duke and senior author of the study.
The study was published on August 10 in Cell Transplantation.
Lead author Brian Diekman, Ph.D said the scientists observed markers of inflammation and noted that the stem cells affected the joint’s inflammatory environment following injury.
“The stem cells changed the levels of certain immune factors, called cytokines, and altered the bone healing response,” stated Diekman.
The Duke team used mesenchymal stem cells isolated from bone marrow. Bone marrow stem cells are very rare; making isolation difficult and requiring that the isolated cells be cultured in the lab under low-oxygen conditions.
“We found that by placing the stem cells into low-oxygen conditions, they would grow more rapidly in culture so that we could deliver enough of them to make a difference therapeutically,” Diekman said.
A richer source of mesenchymal cells is adipose (fat) tissue. Therapeutic doses of MSCs are routinely harvested from fat tissue and do not require culturing in the lab. However, it does takes 5 five days to thoroughly test the adipose cell samples for aerobic bacteria, anaerobic bacteria and endotoxins.
April 19, 2012 by
Stem cells back from outer space may solve mysterious illnesses of astronauts
Astronauts have a much higher incidence of infections in comparison to humans living under normal gravity. Dr. Millie Hughes-Fulford from the molecular biology department of University of California San Francisco is trying to figure out what may cause this difference. As part of her experiments she has been studying the stem cells that give rise to blood and immune system cells, called hematopoietic stem cells. Today, Dr. Hughes-Fulford is expecting to receive 16 mice that were flown on the Space Shuttle Discovery for two weeks. Various aspects of the stem cells and the immune system will be studied.
The importance of understanding zero-gravity associated immune deficiency comes from the aim of establishing long-term space missions to places like mars, in which the current immune deficiencies observed may take a larger toll on the astronauts. Dr. Hughes-Fulford stated that "many of the conditions found in astronauts are similar to muscular-skeletal diseases in
paralyzed or comatose patients on Earth" she continued to state that she has seen young astronauts come down with shingles, which commonly occur in people past the age of 60.
Over the years I’ve been able to do several experiments on the shuttle, Hughes-Fulford said. We’ve found that the immune system is
suppressed when it doesn’t have gravity.
In the previous George W. Bush administration, after the Space Shuttle Columbia disintegrated on re-entry in 2003, the work on stem cells and space travel lost funding. Hughes-Fulford, Almeida, and other U.S. scientists were able to get access to space-bound missions only because of personal and institutional partnerships, however NIH funding was not permitted despite the adult stem cell nature of the experiments. Hughes-Fulford hopes the Obama administration will make it easier to conduct such spaceflight experiments. This time, Dr. Hughes-Fulford was able to send 16 mice in climate-controlled containers along with Discovery. Her team will analyze how mouse white blood cells respond to a simulated infection during flight and upon return, and compare that with how white blood cells behave in 16 Earthbound mice.
Her results from previous flight experiments are pretty compelling, said Daniel Bikle, professor of medicine and dermatology at UC San Francisco. He continued If there’s any failure of these stem cells to differentiate into normal tissues, that could cause problems, he said. If we ever do get around to sending somebody to Mars and somebody gets pregnant, if stem cells fail to differentiate you wouldn’t get a normal baby.
March 31, 2012 by
Making Blood Cells into Heart Cells
Vojdani et al. Hum Cell. 2011 Mar;24(1):35-42
One of the major debates in the area of stem cell therapy is whether adult stem cells are capable of directly transforming (differentiating) into new tissue, or whether the therapeutic effects of administered stem cells occur because of growth factors produced by the injected stem cells. There are supporting data for both possibilities. The direct differentiation of adult stem cells into damaged tissue is supported by studies showing donor-derived adult tissue formed in patients treated. However in many situations that amount of new tissue found is relatively small. Supporting the “growth factor” hypothesis are numerous studies showing that administration of the tissue culture media that the stem cells have been grown in is capable of eliciting therapeutic effects.
Besides adult stem cells differentiating into other cells, there is some belief that other cells of the body are capable of this “transdifferenetiation” ability. For example, there was some work suggesting that B cells are capable of transforming into monocytes. There is some similarity between memory T and B cells with stem cells in that both of them express telomerase in a similar manner as stem cells. Therefore it would be interesting to see if B or T cells may express potential for differentiation into other cells. This is what was investigated in a recent paper (Vojdani et al. Cardiomyocyte marker expression in a human lymphocyte cell line using mouse cardiomyocyte extract. Hum Cell. 2011 Mar;24(1):35-42)
The investigators used a human B cell line called Raji. These cells are immortalized, therefore they may express some of the properties associated with pluripotency. What I mean is that generally cancer cells seem to start reexpressing proteins associated with “earlier” cells and possibly stem cells. For example, cancer cells are known to start re-expressing embryonic stem cell markers such as Oct-4 (Huang et al. Med Oncol. 2011 May 1).
Usually stem cells are made to differentiate into various tissues by exposing them to extracts of the cells that you want them to become. By extracts is usually meant the protein content of the cells after breaking up the cells either through freeze-thaw, sonication, or hypotonic lysis. In the current experiment the Raji cells were “retrodifferentiated” by treatment with 5-azacytidine, which is a DNA methylase inhibitor, as well as the HDAC inhibitor trichostatin A. These chemicals act to remove methylation of the cells, as well as to “open up” the histones by allowing for histone acetylation, respectively. To these undifferentiated cells the extracts from mouse heart cells were added. An interesting method of adding the extracts was used. The cell membrane was temporarily permeabilized and the extracts were added.
After 10 days, 3, and 4 weeks the cells started adhering and expressed a morphology similar to heart cells. Interestingly the cells stated expressing myosin heavy chain, α-actinin and cardiac troponin T after 3 and 4 weeks. Flow cytometry confirmed these data. In cells exposed to trichostatin A and 5-aza-2-deoxycytidine and permeabilized in the presence of the cardiomyocyte extract, troponin T expression was seen in 3.53% of the cells and 3.11% of them expressed α-actinin. These data suggest that pluripotency may be expressed by cells other than conventional stem cells. These experiments are similar to those performed by Collas’ group who demonstrated that administration of cytoplasm from Jurkat T cells to fibroblasts is capable of inducing the transdifferentiation of fibroblasts into cells that express T cell receptor and are capable of secreting IL-2 in response to ligation of the T cell receptor. This reminds us of the opposite of reprogramming by nuclear transfer (eg cloning).
February 13, 2012 by
Rare Heart Defect Reproduced in Petri Dish, Hope for Cure
Dr. Ananya Mandal, MD
A team of researchers has created beating heart cells in the lab using skin cells of children with a rare heart defect. The team, led by Ricardo Dolmetsch of Stanford University took skin cells from children with Timothy syndrome, a rare heart condition commonly associated with autism, as well as syndactyly (webbing of fingers and toes).
The process the team underwent included reprogramming the stem cells and then developing them into cardiac cells in order to have a human model to test on, instead of mice models. “Because every cell in our body has the same genetic programming, that means we can take skin cells and reprogram them to generate stem cells, and we can take those cells to make heart cells,” said Dolmetsch.
Once the heart cells were developed, the team then used them to test several heart rhythm drugs. Unfortunately, none of the drugs initially tested corrected the heart problems associated with Timothy syndrome. However, further research and testing resulted in the discovery of the success of a cancer compound roscovitine, which is now in phase 2 clinical trials. Dolmetsch added that “The potential is really large”, Stanford has applied for patents on this technology and several drug companies have expressed interest in this research.
February 6, 2012 by
First Scientist to identify stem cells dies at 84
Thomas Maugh II, Washington Post
Ernest Armstrong McCulloch, 84, passed away January 20 in his hometown of Toronto. Dr. McCulloch, a medical doctor who attended the University of Toronto is best remembered as the first, along with biophysicist James E. Till, to isolate and identify a stem cell.
Their discovery was reached while both were young researchers at the Ontario Cancer Institute at Princess Margaret Hospital. The discovery came as somewhat of an accident while studying the effects of ionizing radiation on mice. The aim of their study was to attempt to learn how exposure to radiation from nuclear weapons killed and also how radiation destroyed tumors. The mice were irradiated to the point that they would die within 30 days without an infusion of undamaged bone marrow cells. Shortly after injecting the cells, Dr. McCulloch discovered nodules in the spleen. His background in bacteriology allowed him to form the hypothesis that these nodules were the source of replenishing blood cells that were keeping the mice alive. These results were published, however received very little attention. Two years later, after hundreds of hours of intensive research, McCulloch and Till published a paper proving that all three types of blood cells – red, white, and platelets were produced by a single stem cell.
This discovery was the precursor for bone marrow transplant therapy, a treatment which has been utilized for 40 years and saved countless lives. “Without their work, we would never have had bone marrow transplants,” Michael Rudnicki, scientific director of the Stem Cell Network, told the Toronto Star. “We might have muddled our way through it . . . but their work provided the theoretical underpinnings for bone marrow transplant as a therapy, which has been in the clinic now for 40 years and has saved countless lives.”
February 6, 2012 by
Therapeutic Effects of Intra-Arterial Delivery of Bone Marrow Stromal Cells in Traumatic Brain Injury of Rats—In Vivo Cell Tracking Study by Near-Infrared Fluorescence Imaging
Neurosurgery:
February 2012 – Volume 70 – Issue 2 – p 435–444
doi: 10.1227/NEU.0b013e318230a795
Research-Animal
Osanai, Toshiya MD, PhD*; Kuroda, Satoshi MD, PhD*; Sugiyama, Taku MD, PhD*; Kawabori, Masahito MD*; Ito, Masaki MD*; Shichinohe, Hideo MD, PhD*; Kuge, Yuji PhD‡; Houkin, Kiyohiro MD, PhD*; Tamaki, Nagara MD, PhD‡; Iwasaki, Yoshinobu MD, PhD*
Abstract
BACKGROUND: A noninvasive and effective route of cell delivery should be established to yield maximal therapeutic effects for central nervous system (CNS) disorders.
OBJECTIVE: To elucidate whether intra-arterial delivery of bone marrow stromal cells (BMSCs) significantly promotes functional recovery in traumatic brain injury (TBI) in rats.
METHODS: Rat BMSCs were transplanted through the ipsilateral internal carotid artery 7 days after the onset of cortical freezing injury. The BMSCs were labeled with fluorescent dye, and in vivo optical imaging was employed to monitor the behaviors of cells for 4 weeks after transplantation. Motor function was assessed for 4 weeks, and the transplanted BMSCs were examined using immunohistochemistry.
RESULTS: In vivo optical imaging and histologic analysis clearly demonstrated that the intra-arterially injected BMSCs were engrafted during the first pass without systemic circulation, and the transplanted BMSCs started to migrate from the cerebral capillary bed to the injured CNS tissue within 3 hours. Intra-arterial BMSC transplantation significantly promoted functional recovery after cortical freezing injury. A subgroup of BMSCs expressed the phenotypes of neurons, astrocytes, and endothelial cells around the injured neocortex 4 weeks after transplantation.
CONCLUSION: Intra-arterial transplantation may be a valuable option for prompt, noninvasive delivery of BMSCs to the injured CNS tissue, enhancing functional recovery after TBI. In vivo optical imaging may provide important information on the intracerebral behaviors of donor cells by noninvasive, serial visualization.
February 3, 2012 by
Inhaling Stem Cells for Treating Parkinson’s
Danielyan et al. Rejuvenation Res.
Stem cells have been delivered in a variety of ways: intravenously, into the spinal canal (intrathecally), into the brain (stereotactically), into the joint (intra-articularly), and into the cardiac muscle (endocardially). Scientists from the Department of Clinical Pharmacology, University Hospital of Tübingen , Tübingen, Germany have reported today a new way of delivering stem cells: via the nose.
Previous experiments administering stem cells for the treatment of Parkinson’s were primarily aimed at injection directly into the brain using sterotactic methods. These methods are highly invasive and there is always the potential of causing injury. Additionally some groups have used intravenous administration but the washout and number of cells being stuck in the lung and liver was reported as a potential problem.
The promise of using stem cells for the treatment of Parkinson’s comes not only from the direct regenerative ability of stem cells such as mesenchymal stem cells, but also from the fact that Parkinson’s is associated with inflammatory cytokine production, which has been previously demonstrated to be inhibited by stem cell administration.
Intranasal administration of bone marrow mesenchymal stem cells was performed in rats induced to develop a Parkinson’s like disease in which the dopaminergic cells were killed by administration of the toxin 6-hydroxydopamine (6-OHDA).
In rats that received the stem cells intranasally it was possible to find stem cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord. Out of 1 × 10(6) MSCs applied intranasally, 24% of the stem cells could be detected for least 4.5 months in the brains of 6-OHDA rats. It appears that the stem cells administered actually could proliferate in vivo as shown by expression of proliferating cell nuclear antigen on the administered mesenchymal stem cells.
Functionally it appeared that the intranasal administration increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra, and completely eliminated the 6-OHDA-induced increase apoptotic cells as detected by TUNEL. Decreases in dopamine were prevented by cellular administration. A decrease in the inflammatory cytokines TNF, IFN-g, IL-2, 2, 6, and 12 was observed to be associated with the administration of cell therapy.
It will be interesting to see if this easy to apply technique will enter clinical trials. Already clinical trials are using non-conventional means of stem cell administration, for example the topical application of stem cells for burn wounds, which is being performed by Dr. Amit Patel from the University of Utah, who we interviewed for the Cellmedicine news blog above.
