July 30, 2012 by

Why does fat (adipose) stem cell therapy take more than one week?

Intravenously administered adipose-derived stem cells will tend to migrate back to the fresh wound site if it is not given an adequate time to heal. Therefore, it is essential to allow about one week after the mini-liposuction before administering any stem cells intravenously. Otherwise, there is a likelihood that the treatment will not be as effective. Additionally, it takes 5 five days to thoroughly test the adipose cell samples for aerobic and anaerobic bacteria as well as endotoxins.

In order to ensure that no patient receives an infected sample, at least 5 days must transpire before the cells can be confirmed safe and injected back into the patient.

Lastly, this 5-day waiting period enables our scientists to culture a small sample of each patient’s stem cells in the lab to observe how they are likely to proliferate once they are inside the body. If a patient’s cells show low viability, Stem Cell Institute doctors will supplement the treatment with additional cord-derived cells to compensate. The same can be done in cases of low cell yield.

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Osteoarthritis, Rheumatoid Arthritis, Stem Cell Research Tagged With: , , , , ,
May 21, 2012 by

Multiple Sclerosis Treatment Success Using Mesenchymal Stem Cell-Secreted Factors in Animal Model

Stem cell researchers at Case Western Reserve have reported in Nature Magazine that the functional deficits caused by multiple sclerosis can be reduced by administering mesenchymal stem cell secreted factors.

While previous studies have shown promising results using mesenchymal stem cells, this is the first time that such results have been reported without using the stem cells themselves.

The Stem Cell Institute’s Founder, Neil Riordan PhD, originally cited the potential therapeutic role of mesenchymal stem cell trophic factors in the 2010 Cellular Immunology publication: Mesenchymal Stem Cells as Anti-inflammatories: Implications for Treatment of Duchenne Muscular Dystrophy

In addition to reducing functional deficits, the development of new myelinating oligodendrocytes and neurons, release of inflammatory cytokines, and suppression of immune cells influx were also observed in the Case Western study.

Details can be found here: http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.3109.html

Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models

Lianhua Bai, Donald P Lennon, Arnold I Caplan, Anne DeChant, Jordan Hecker, Janet Kranso, Anita Zaremba Robert H Miller

Nature Neuroscience (2012) doi:10.1038/nn.3109
Received 18 January 2012 Accepted 17 April 2012 Published online 20 May 2012

Abstract

Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research Tagged With: , , , , ,
April 7, 2012 by

First patient to get stem cell therapy identified

By Rob Stein, The Washington Post
Embryonic stem cells have numerous pitfalls in addition to the ethical dilemmas. While the concept of a “blank slate” cell is extremely attractive in terms of generating new tissues for transplantation and organ replacement, the problem is that these cells are so young that they do not properly “know” how to integrate with existing tissues. This causes the problem of possible dysfunction of the cellular products made from the cells, but also causes the issue of cancer formation. Many studies have demonstrated that administration of embryonic stem cells, or products made from them form cancers when injected into mice that lack an immune system.
Because of the risks associated with embryonic stem cells, the FDA has been historically reluctant to allow initiation of clinical trials with them. The leader of the field of embryonic stem cells is Geron, the company that funded the research that lead to the discovery of human embryonic stem cells, as well as the company that has the exclusive license for their commercial use. The business of embryonic stem cells is associated with large financial investments. Specifically, patents are not only associated with the cells themselves but one methods of growing the cells and methods of selecting the cells to reduce the possibility of cancer formation. In some ways people believe that embryonic stem cells are an exercise in science because adult stem cells have been demonstrated to elicit numerous therapeutic effects without the risks.
Last year a monumental study was initiated in that the FDA allowed for the first human use of an embryonic stem cell product. The company Geron was granted approval to treat patients with spinal cord injury using embryonic stem cell derived oligodendrocytes, the cells that generate the myelin that lines the nerves.
Today, information was released on the first patient that was treated with these cells. The patient was a partially paralyzed young man, Timothy J. Atchison, 21, known to family and friends as T.J.
T.J. was a student at the University of Alabama College of Nursing when he was partially paralyzed in a Sept. 25 car accident, his aunt and father said. He agreed to let doctors infuse more than 2 million cells made from stem cells into his spine 13 days later at the Shepherd Center in Atlanta, according to his aunt and a family friend.
While the primary endpoint of the trial is to demonstrate safety, doctors are also testing whether the cells restore sensation and movement. It was too soon to tell whether the cells were helping T.J., Angela Atchison said. “They said it would be about a year before they’ll know if there’s any difference — if it takes,” she said. “We’re just hoping and praying that it works.”
T.J.’s father, Timothy Atchison of Millry, said his son had maintained a positive attitude, beginning when he was in the emergency room after the accident. and understood how seriously he was injured.
“He said, whatever the Lord leaves him with, he’ll do the best he can with it,” the father said in a phone interview Monday. He would not directly acknowledge that his son was in the stem cell study, but confirmed details including his Shepherd Center treatment. “I’ll put it this way, they tested a lot of folks, and only one made the cut,” he said during another interview Tuesday. “You can read between the lines.”

Filed Under: Clinical Trials, News, Stem Cell Research Tagged With: , ,
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).

Filed Under: Heart Disease, News, Stem Cell Research Tagged With: , , , ,
March 17, 2012 by

Stemedica Treats First Patient with Ischemic Allogeneic Mesenchymal Stem Cells

Stemedica Cell Technologies Press Release
The San Diego stem cell company Stemedica Cell Technologies, Inc reported treatment of its first patient as part of a 35 patient clinical trial in stroke patients. The study uses bone marrow stem cells that have been preconditioned with hypoxia and used in a non-matched manner. The trial is being conducted at the University of California San Diego and is titled “A Phase I/II, Multi-Center, Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of a Single Intravenous Dose of Allogeneic Mesenchymal Bone Marrow Cells to Subjects with Ischemic Stroke.”
Every year more than 800,000 Americans suffer a stroke. According to the American Heart Association, stroke is the fourth leading cause of death – costing an estimated $73.7 billion in 2010 for stroke-related medical costs and disability.
The study’s Principle investigator is Michael Levy, MD, PhD, FACS, chief of pediatric neurosurgery at Children’s Hospital San Diego (CHSD) and professor of neurological surgery at UCSD. The aim of the trial is to determine tolerance and therapeutic outcomes for intravenously-delivered adult allogeneic mesenchymal stem cells and to hopefully pave the way for a new therapeutic category of treatment for ischemic stroke. When asked about the first patient in the study, Dr. Levy said, “The treatment went smoothly; no side effects were observed, and the patient was released from the hospital the next day.”
Lev Verkh, PhD, Stemedica’s chief regulatory and clinical development officer, commented: “Many years of research and hard work by the Stemedica team culminated today in the treatment of the first patient using our uniquely designed stem cells to be effective under ischemic condition. We are proud to be the first company to initiate a study such as this under a clinical protocol approved by the U.S. Food and Drug Administration (FDA).”
Several companies are using stem cells for stroke. For example the company Aldagen is using bone marrow derived cells from the same patient. Their approach involves bone marrow extraction, purification of a selected stem cell from the bone marrow, and subsequent administration of the cell into the patients. The reason why stroke is of great interest to many companies is because recent studies have demonstrated that the brain has its own stem cells that start multiplying after a stroke. Unfortunately these stem cells that are already existing are not found in a high enough number to cause a substantial repair. The idea is that when new stem cells are added, they assist the existing stem cells in supporting the repair process.
“This clinical trial marks a significant achievement in the treatment of debilitating ischemia-related pathologies including ischemic stroke,” said Nikolai Tankovich, MD, PhD, president and chief medical officer of Stemedica. “We believe these specially designed mesenchymal stem cells are able to tolerate, survive and repair ischemic tissues caused by an infarction of the brain, heart, kidney, retina and other organs. In addition, these mesenchymal stem cells are capable of up regulating an array of important genes that are essential for the synthesis of critical proteins involved in recovery.”
Dr. Verkh continued, “Patients in this study have significant functional or neurologic impairment that confines them to a wheelchair or requires home nursing care or assistance with the general activities of daily living and have received the ischemic stroke diagnosis at least six months prior to enrollment in this study”.
The inclusion/exclusion criteria are:
Inclusion Criteria:
•Clinical diagnosis of ischemic stroke for longer than 6 months
•Brain CT/MRI scan at initial diagnosis and at enrollment consistent with ischemic stroke
•No substantial improvement in neurologic or functional deficits for the 2 months prior to enrollment
•NIHSS score between 6-20
•Life expectancy greater than 12 months
•Prior to treatment patient received standard medical care for the secondary prevention of ischemic stroke
•Adequate organ function as defined by the following criteria:
Exclusion Criteria:
•History of uncontrolled seizure disorder
•History of cancer within the past 5 years.
•History of cerebral neoplasm
•Positive for hepatitis B, C or HIV
•Myocardial infarction withing six months of study entry
•Findings on baseline CT suggestive of subarachnoid or intracerebral hemorrhage within past 12 months.
•Allergies to Bovine or Porcine products

Filed Under: Adult Stem Cells, Clinical Trials, News, Stem Cell Research, Stem Cell Therapy, Stroke Tagged With: , , , , ,
February 15, 2012 by

Stem Cells in Theory and Practice

Dr. Douglas J. Herthel of Alamo Pintado Equine Medical Center in Los Olivos, California was one of the first practitioners to use stem cells, beginning in 1995. Herthel used stem cells from bone marrow to treat ligament and tendon injuries in horses. The results from these treatments were so promising that he began using stem cells to treat other various conditions as well.

The treatment has since been used to treat common equine issues such as laminitis, as well as spinal cord injuries. A dramatic example is that of a donkey who suffered a spinal cord injury as was quadriplegic. The donkey regained full function following a stem cell treatment. “It’s certainly an exciting time to be in the veterinary field,” Dr. Herthel said. “You’re talking about potential cures for things, rather than just palliation. And you’re also talking about maybe less pharmacological use.” Adair, an Irish Draught Cross horse had a very severe case of chronic forelimb laminitis, so severe in fact, that without a dramatic improvement he would have to be euthanized. Adair was treated with stem cells in early 2010, 48 hours following treatment he appeared to be in less pain and six weeks later, his hooves had grown almost halfway back.

Dr. Johnson, Adair’s owner, started using stem cells in 2001 to treat tendinitis in racehorses. “The funny thing about science or lack thereof in clinical practice is you try something for what has historically not been an easy problem to fix, and you have some limited success, and you carry on,” Dr. Johnson said. Some doctors performing stem cell treatment extract and process the cells in house, while others order stem cells from another horse. Many doctors send tissue samples to Vet-Stem Inc. or other laboratories to process the cells. Dr. Robert J. Harman, Vet-Stem’s chief executive officer, said his company has processed stem cells from fat samples for about 8,000 patients since starting in 2004. About 4,000 veterinarians have completed the Vet-Stem credentialing course on stem cells as a therapy. “Once they’ve been through the course, most people are pretty strong believers that this has a place in veterinary medicine,” Dr. Harman said.

Vet-stem treats mostly horses, as well as some dogs and cats. The treatments for horses are generally for tendon and ligament injuries, while most dogs receive treatment for arthritis. Many of the dogs treated are athletes, but some are also family pets. While this is good news for people who want to see the best treatment given to man’s best friend, others caution against getting too excited over the current stem cell therapies.

Dr. Brennen A. McKenzie of Adobe Animal Hospital in Los Altos, California believes that the evidence of efficacy is preliminary. He believes that the clinics should offer the treatment as an experimental treatment in the form of a clinical trial.

A new organization, the North American Veterinary Regenerative Medicine Association, is seeking to act as a clearinghouse of information on stem cells in veterinary medicine, said Dr. Owens, director of the UC-Davis Regenerative Medicine Laboratory and NAVRMA secretary-treasurer. Hundreds of practitioners and researchers have expressed interest in being a member of the NAVRMA, and the first meeting will be in June.

The FDA has the authority to regulate the use of stem cells in animals, as they have done in humans. However, as of yet there are no specific regulations regarding the treatment of animals with stem cells.

Filed Under: News, Stem Cell Research Tagged With: , , , , , , ,
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.

Filed Under: Heart Disease, News, Stem Cell Research Tagged With: , , , , , ,
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.”

Filed Under: News, Stem Cell Research Tagged With: , , ,
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.

Filed Under: Adult Stem Cells, News, Stem Cell Research Tagged With: , , ,
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.

Filed Under: News, Parkinson's, Stem Cell Research Tagged With: , , , , , , ,
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