Medistem Advances Type 1 Diabetes Stem Cell Technology Licensed From Yale

SAN DIEGO, CA — (Marketwire) — 09/12/12 — Medistem Inc. (PINKSHEETS: MEDS) announced today completion of the first phase of a joint project with the Shumakov Research Center of Transplantology and Artificial Organs of the Russian Federation and its Russian and CIS licensee ERCell. The collaboration is based on using Endometrial Regenerative Cell (ERC) technology licensed from Yale University to treat type 1 diabetes.

Dr. Viktor Sevastianov, Head and Professor of the Institute of Biomedical Research and Technology, within the Shumakov Center, demonstrated safety and feasibility of ERC injection in experimental animal models of diabetes. Additionally, the studies demonstrated that the cell delivery technology developed by Dr. Sevastianov’s laboratory can be used to enhance growth of ERC. These experiments are part of the process for registration of “new pharmacological substances,” which is the first step towards drug approval in Russia.
“Type 1 diabetes is a significant problem in the Russian Federation. Our laboratory has been working developing various delivery formulations for cell therapy, such as SpheroGel, which is registered in Russia,” said Dr. Sevastianov. “Given that the ERC can be produced in large quantities, is a universal donor cell, and already is approved for clinical trials in both the USA and Russia, we are optimistic our collaboration will lead to a viable commercial product for the type 1 diabetes Russian population.”
Medistem discovered ERCs in 2007, and they appear to possess “universal donor” properties, allowing the cells derived from one donor can treat multiple unrelated recipients. According to Medistem’s current FDA cleared production scheme, one donor can generate 20,000 patient doses. Medistem licensed technology from Yale University for generating insulin producing cells from ERC. A publication describing the technology may be found at http://www.ncbi.nlm.nih.gov/pubmed/21878900.

“Our vision is to combine SpheroGel, which is a clinically-available cell delivery vehicle in Russia, together with Medistem’s ERC and technology from Yale University to generate a commercially-viable product for clinical trials in type 1 diabetes patients,” said Thomas Ichim, CEO of Medistem.

Medistem has outlicensed the Russian and CIS rights to ERC and related products to ERCell LLC, a St. Petersburg-based biotechnology company. Under the agreement, Medistem owns all data generated and will receive milestone and royalty payments.
“By working with leading investigators in Russia and the USA, we seek to be the leaders in a new era of medicine in Russia,” said Tereza Ustimova, CEO of ERCell.”

Cautionary Statement This press release does not constitute an offer to sell or a solicitation of an offer to buy any of our securities. This press release may contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking information. Factors which may cause actual results to differ from our forward-looking statements are discussed in our Form 10-K for the year ended December 31, 2007 as filed with the Securities and Exchange Commission.

Contact: Thomas Ichim Chief Executive Officer Medistem Inc. 9255 Towne Centre Drive Suite 450 San Diego, CA 92122 858 349 3617 www.medisteminc.com twitter: @thomasichim
Source: Medistem Inc.

Blood Stem Cells Permanently Damaged by Alcohol

Bone marrow stem cells are extremely sensitive to the primary by-product of alcohol, which causes permanent damage to their DNA claims researchers from the Medical Research Council (MRC) Lab of Molecular Biology.

The research, which was conducted on mice, uncovers two mechanisms that normally control this type of damage; a protein group that recognizes and repairs DNA damage and an enzyme that eliminates acetaldehyde, alcohol’s toxic breakdown product.

Mice lacking both protective mechanisms developed bone marrow failure stemming from blood stem cell damage.
These results mark the first time that scientists have been able to explain why bone marrow fails in Fanconi anemia (FA) patients. FA is a rare genetic disorder.

The report concludes that FA turns off the bone marrow’s “repair kit” via FA gene mutation which causers DNA damage from acetaldehyde to continue unchecked. This damage is responsible for bone marrow failure and developmental defects in FA patients and makes them especially vulnerable to blood and other types of cancer.

These findings may have particular significance for the world’s Asian population, many of whom suffer from “Asian flush syndrome”. People with AFS lack the enzyme ALDH2 and therefore could be particularly susceptible to DNA damage. The authors warned that this subset of the Asian population could suffer permanent DNA damage with alcohol consumption and be more highly prone to blood cancer, bone marrow failure and premature aging than the Asian population at-large.

“Blood stem cells are responsible for providing a continuous supply of healthy blood cells throughout our lifespan. With age, these vital stem cells become less effective because of the build up of damaged DNA. Our study identifies a key source of this DNA damage and defines two protective mechanisms that stem cells use to counteract this threat. Last year we published a paper showing that without this two-tier protection, alcohol breakdown products are extremely toxic to the blood. We now identify exactly where this DNA damage is occurring, which is important because it means that alcohol doesn’t just kill off healthy circulating cells, it gradually destroys the blood cell factory. Once these blood stem cells are damaged they may give rise to leukaemias and when they are gone they cannot be replaced, resulting in bone marrow failure,” Dr KJ Patel, who is the primary investigator.

“The findings may be particularly significant for a vast number of people from Asian countries such as China, where up to a third of the population are deficient in the ALDH2 enzyme. Alcohol consumption in these individuals could overload their FA DNA repair kit causing irreversible damage to their blood stem cells. The long-term consequences of this could be bone marrow dysfunction and the emergence of blood cancers,” Patel added.

“This study provides much sought-after explanation of the biology underpinning the devastating childhood disease Fanconi anemia. In future this work may underpin new treatments for this genetic disease, which currently is associated with a very poor prognosis. It also helps to inform large numbers of the global population, who are deficient in the ALDH2 enzyme, that drinking alcohol may be inflicting invisible damage on their DNA,” commented Sir Hugh Pelham, director of the MRC Laboratory of Molecular Biology.

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.

Ref: Stem Cell Therapy for Osteoarthritis

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.

Endometrial Stem Cells Yeild Postive Clinical Trial Results for Heart Disease

More progress reported on the treatment of heart disease with endometrial stem cells. Neil Riordan, PhD is one of the early pioneers of endometrial stem cell technology. Dr. Riordan is also the Founder and President of the Stem Cell Institute in Panama City, Panama.

Positive Two-Month Data From RECOVER-ERC Congestive Heart Failure Trial

SAN DIEGO, CA–(Marketwire – Jun 4, 2012) – Medistem Inc. (PINKSHEETS: MEDS) announced today positive safety data from the first 5 patients enrolled in the Non-Revascularizable IschEmic Cardiomyopathy treated with Retrograde COronary Sinus Venous DElivery of Cell TheRapy (RECOVER-ERC) trial. The clinical trial uses the company’s “Universal Donor” Endometrial Regenerative Cells (ERC) to treat Congestive Heart Failure (CHF).

According to the study design, after 5 patients enter the trial, they must be observed for a two month time period before additional patients are allowed to enter the study. Patient data was analyzed by the study’s independent Data Safety Monitoring Board (DSMB), which concluded that based on lack of adverse effects, the study be allowed to continue recruitment.

“Medistem is developing a treatment for CHF that uses a 30-minute catheter-based procedure to administer the ERC stem cell into the patients’ hearts. The achievement of 2 month patient follow-up with no adverse events is a strong signal for us that our new approach to this terrible condition is feasible,” said Thomas Ichim, CEO of Medistem.

The RECOVER-ERC trial will treat a total of 60 patients with end-stage heart failure with three concentrations of ERC stem cells or placebo. The clinical trial is being conducted by Dr. Leo Bockeria, Chairman of the Backulev Centre for Cardiovascular Surgery, in collaboration with Dr. Amit Patel, Director of Clinical Regenerative Medicine at University of Utah.

“As a professional drug developer, I am very optimistic of a stem cell product that can be used as a drug. The ERC stem cell can be stored frozen indefinitely, does not need matching with donors, and can be injected in a simple 30-minute procedure into the heart,” said Dr. Sergey Sablin, Vice President of Medistem and co-founder of the multi-billion dollar NASDAQ company Medivation.

Currently patients with end-stage heart failure, such as the ones enrolled in the RECOVER-ERC study, have no option except for heart transplantation, which is limited by side effects and lack of donors. In contrast to other stem cells, ERC can be manufactured inexpensively, do not require tissue matching, and can be administered in a minimally-invasive manner. Animal experiments suggest ERC are more potent than other stem cell sources at restoring heart function. The FDA has approved a clinical trial of ERC in treatment of critical limb ischemia in the USA.

About Medistem Inc.
Medistem Inc. is a biotechnology company developing technologies related to adult stem cell extraction, manipulation, and use for treating inflammatory and degenerative diseases. The company’s lead product, the endometrial regenerative cell (ERC), is a “universal donor” stem cell being developed for critical limb ischemia and heart failure. A publication describing the support for use of ERC for this condition may be found at http://www.translational-medicine.com/content/pdf/1479-5876-6-45.pdf.

Cautionary Statement
This press release does not constitute an offer to sell or a solicitation of an offer to buy any of our securities. This press release may contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking information. Factors which may cause actual results to differ from our forward-looking statements are discussed in our Form 10-K for the year ended December 31, 2007 as filed with the Securities and Exchange Commission.

Medistem Contact:

Thomas Ichim
Chief Executive Officer
Medistem Inc.
9255 Towne Centre Drive
Suite 450
San Diego
CA 92122
858 349 3617
858 642 0027
www.medisteminc.com
twitter: @thomasichim

Fat Stem Cells are not affected by weight or age

Mojallal et al. Aesthetic Plast Surg.
Fat represents a potent source of autologous stem cells. Historically, the majority of research using autologous stem cells involved stem cells collected from the bone marrow. This source is associated with a painful extraction procedure and relatively low concentrations of mesenchymal stem cells. In contract, mini-liposuctions represent a less invasive extraction approach. Additionally, adipose tissue has been shown to contain substantially higher number of mesenchymal stem cells as well as hematopoietic stem cells and endothelial progenitor cells.
The use of fat derived stem cells has grown exponentially in recent years for numerous indications. Perhaps the largest data set for fat derived stem cells is possessed by Dr. Bob Harman from Vet Stem, who has treated a total of more than 10,000 large animals with this procedure. The Cellmedicine clinic has had an excellent track record of success using autologous fat for treatment of multiple sclerosis having treated more than 200 patients.
One of the major limiting factors of stem cell therapy using your own stem cells (autologous) is that the potency and number of stem cells is believed to decrease with age and disease. These studies, however, have been performed primarily from bone marrow sources of stem cells. Any hematologist will tell you that with age the bone marrow becomes drier and possesses less cells. Studies have shown that bone marrow stem cells from patients with diabetes or from obese patients have less activity as compared to age matched controls. There has been some thought that the stem cells in the adipose tissue are protected from age and disease. A current study (Mojallal et al. Influence of Age and Body Mass Index on the Yield and Proliferation Capacity of Adipose-Derived Stem Cells. Aesthetic Plast Surg. 2011 May 26) from the Service de Chirurgie Plastique, Reconstructrice et Esthétique in Lyon France sought to address this. The investigators assessed 42 women who were divided into two groups: age ≤ 40 or >40 and BMI ≤ 25 or >25. Fat tissue was harvested via manual lipoaspiration from the abdominal region. After centrifugation, 100 ml of lipoaspirate was sent to the laboratory for isolation and cultivation of ASCs. The investigators found that average cell yield was 0.380 × 10(6)/ml. Cell yield and proliferation capacity did not show statistically significant correlation to the age and BMI of patients, nor was there a statistically significant difference between cell yield and proliferation capacity between the different groups.
The study looked at some very basic parameters: cell number, viability and proliferative ability. It may be that adipose stem cells may exhibit differences in immune modulatory potential or differentiation potential between donors. This was not assessed. Additionally, the adipose derived cells were not assessed between donors suffering from different conditions. Despite these shortcomings, the data appears to support the hypothesis that adipose derived stem cells may have some advantages as compared to bone marrow stem cells, at least for autologous uses.

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.

Adult Stem Cell Therapy Successfully Treats Spinal Cord Injury

An interesting spinal cord injury study was published last week. The Turkish researchers tested two types of stem cells on spinal cord injured mice. The two cell types were native bone marrow cells and cultured repair stem cells called Mesenchymal stem cells. Native bone marrow cells contain bone marrow forming stem cells as well as a small number of Mesenchymal stem cells.

After injuring the spinal cords, the stem cells were implanted at the site of the injury. The control mice that received no cells had no improvement in neural activity. The mice that received both cell types had improved neural activity. The cultured Mesenchymal stem cell group improved significantly more than the native bone marrow stem cell group.

Stem Cell Rev. 2012 May 3. [Epub ahead of print]
Stem Cell Therapy in Spinal Cord Injury: In Vivo and Postmortem Tracking of Bone Marrow Mononuclear or Mesenchymal Stem Cells.
Ozdemir M, Attar A, Kuzu I, Ayten M, Ozgencil E, Bozkurt M, Dalva K, Uckan D, Kılıc E, Sancak T, Kanpolat Y, Beksac M.

Source
School of Medicine, Department of Neurosurgery, Pamukkale University, 20070, Kinikli, Denizli, Turkey, drmevci@hotmail.com.

Abstract
OBJECTIVE:
The aim of this study was to address the question of whether bone marrow-originated mononuclear cells (MNC) or mesenchymal stem cells (MSC) induce neural regeneration when implanted intraspinally.

MATERIALS AND METHODS:
The study design included 4 groups of mice: Group 1, non-traumatized control group; Groups 2, 3 and 4 spinal cord traumatized mice with 1 g force Tator clips, which received intralesionally either no cellular implants (Group 2), luciferase (Luc) (+) MNC (Group 3) or MSC (Group 4) obtained from CMV-Luc or beta-actin Luc donor transgenic mice. Following the surgery until decapitation, periodical radioluminescence imaging (RLI) and Basso Mouse Scale (BMS) evaluations was performed to monitor neural activity. Postmortem immunohistochemical techniques were used to analyze the fate of donor type implanted cells.

RESULTS:
All mice of Groups 3 and 4 showed various degrees of improvement in the BMS scores, whereas there was no change in Groups 1 and 2. The functional improvement was significantly better in Group 4 compared to Group 3 (18 vs 8, p = 0.002). The immunohistochemical staining demonstrated GFP(+)Luc(+) neuronal/glial cells that were also positive with one or more of these markers: nestin, myelin associated glycoprotein, microtubule associated protein or myelin oligodendrocyte specific protein, which is considered as indicator of donor type neuronal regeneration. Frequency of donor type neuronal cells; Luc + signals and median BMS scores were observed 48-64 % and 68-72 %; 44-80 %; 8 and 18 within Groups III and IV respectively.

DISCUSSION:
MSCs were more effective than MNC in obtaining neuronal recovery. Substantial but incomplete functional improvement was associated with donor type in vivo imaging signals more frequently than the number of neuronal cells expressing donor markers in spinal cord sections in vitro. Our results are in favor of functional recovery arising from both donor MSC and MNCs, contributing to direct neuronal regeneration and additional indirect mechanisms.

Stem cell therapy for spinal cord injury: Christina Cohen

Christina Cohen, discusses her progress after undergoing stem cell therapy at the Stem Cell Institute in Panama City, Panama. Christina suffered a T-12 injury after falling from a 150 ft cliff. Since then, she has regained movement, greatly reduced her dependency on drugs and regained bladder and partial bowel control.

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.