September 13, 2012 by

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.

Filed Under: Diabetes, News, Stem Cell Research Tagged With: , , , , ,
December 30, 2010 by

Men with Type 1 diabetes eventually may have a way to grow their own pancreas transplants

Thomas H. Maugh II, Los Angeles Times

Researchers from Georgetown University Medical Center in Washington DC reported today at the Annual Meeting of the American Society of Cell Biology that sperm contains stem cells capable of becoming beta cells. The beta cells are the insulin producing cells of the pancreas which are damaged/destroyed in patients with Type 1 diabetes.

Conventionally adult stem cells are found in the bone marrow, fat tissue, and cord blood. Recent studies have identified stem cells in places such as menstrual blood (endometrial regenerative cells), hair follicles, and baby teeth. The finding that stem cells from sperm are capable of generating insulin-producing cells has several major implications. For one, males could theoretically bank their own stem cells and use them in the future. Currently transplants with beta cells or pancreatic transplants have the drawback that there are not enough donors and also that the recipient is required to receive life-long immune suppression.

The lead scientist of the finding is biochemist G. Ian Gallicano of Georgetown and his colleagues obtained tissue from human testes from recently deceased donors and placed them in a special growth medium in the laboratory, where they began producing insulin. “These are true pluripotent stem cells,” he said in a statement. When transplanted into the backs of immune-deficient mice, the cells cured diabetes for about a week before dying. More recent results, Gallicano said, show that the researchers are able to produce more insulin-producing cells and keep them alive longer. The challenge, he noted, is to make them survive for very long periods of time in the recipient.

Dr. Gallicano and his team previous published in the peer reviewed journal Stem Cells and Development (Golestaneh et al. Pluripotent stem cells derived from adult human testes Stem Cells Dev. 2009 Oct;18(8):1115-26) that the testes contains spermatogonial stem cells (SSCs) which are capable of converting to embryonic stem (ES)-like cells which can differentiate into all three germ layers and organ lineages.

The importance of the current research is that these stem cells can actually exhibit function when administered to animals. It will be interesting to see if other organ functions may be restored by use of these stem cells.

Filed Under: Diabetes, News, Stem Cell Research Tagged With: , , , ,
December 15, 2010 by

Stem Cell Institute in Panama Collaborates on New Method of Treating Diabetes-Associated Heart Disease

Zhang et al. Journal of Translational Medicine

Diabetes is associated with numerous “secondary complications” including premature heart disease, renal failure, critical limb ischemia (an advanced form of peripheral artery disease) and diabetic retinopathy. One of the common features of these secondary complications is that they are all associated with low levels of circulating endothelial progenitor cells. We have previously discussed the interaction between inflammation and low levels of circulating endothelial progenitor cells http://www.translational-medicine.com/content/7/1/106. It appears that the uncontrolled sugar levels in the blood cause generation of modified proteins, which initiate low level, chronic inflammation. One of the major mechanisms by which sugar- modified proteins induce inflammation is by stimulating a molecular signaling protein called Toll like receptor (TLR)-4. Generally TLR-4 is used by the body to sense “danger”, that is, to sense pathogens, tissue injury, or various factors that may negatively affect the well-being of the host.

In a collaborative study between Stem Cell Institute Panama, Medistem, and the University of Western Ontario, Canada, it was observed that TLR-4 is associated with induction of heart cell (cardiomyocyte) death in diabetic animals. The scientists demonstrated that suppressing the gene encoding for TLR-4 resulted in prevention of heart disease. The results were published in the article Zhang et al. Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4. J Transl Med. 2010 Dec 15;8(1):133. TLR-4 is known to recognize bacterial endotoxin, fragments of degraded extracellular matrix, as well as the stress protein HMBG-1.

In the current experiment, mice were made diabetic by administration of the islet-specific toxin streptozotocin. Diabetic mice were treated with double stranded RNA specific to the gene encoding TLR4. It is known that when cells are treated with double stranded RNA, the gene that is similar to the double strand is silenced. This process is called “RNA interference”.

Seven days after mice became diabetic, as evidenced by hyperglycemia, the level of TLR4 gene in myocardial tissue was significantly elevated. This suggested that not only does hyperglycemia activate TLR4, which was previously known, but that expression of this pro-inflammatory marker actually is increased. Indeed it may be possible that triggers of TLR4 actually act in an autocrine manner in order to increase cell sensitivity

In order to determine whether TLR4 was associated with the cause of cardiomyocyte death, animals were administered the double stranded RNA in order to suppress levels of TLR4. When this was performed the level of cardiomyocyte death was markedly reduced. This is an important finding since usually scientists think of TLR4 as a molecule that activates inflammation through stimulation of the immune

The authors conclude by stating that new evidence is presented suggesting that TLR4 plays a critical role in cardiac apoptosis. This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene.

The research finding that TLR4 is implicated in death of cardiac cells means that agents that suppress it, such as double stranded RNA, may be useful for incorporation into stem cells in order to make the cardiac cells that are derived from the stem cells resistant to death induced by conditions of stress such as hyperglycemia.

Filed Under: Diabetes, Heart Disease, News, Stem Cell Research Tagged With: , , , , , , , ,
May 11, 2010 by

Transient Inhibition of Transforming Growth Factor-{beta}1 in Human Diabetic CD 34+ Cells Enhances Vascular Reparative Functions

CD34 cells are primarily known for their hematopoietic activity, which means, that they are capable of making blood cells. More recently, studies have demonstrated that a subset of CD34 cells are capable of creating new blood vessel cells called endothelial cells. The ability to made new endothelial cells is important because old/dysfunctional blood vessel cells contribute to risk of stroke or heart attack.

Numerous disease conditions can benefit from increasing the number of healthy new blood vessels. Accordingly, studies have been conducted taking out patient bone marrow cells (which contain high concentrations of CD34 cells) and administering them either intravenously or locally in order to stimulate new blood vessel formation. This procedure has been helpful in patients with advanced peripheral artery disease www.youtube.com/watch?v=OwIOL13vXQ4 , as well as in patients with heart failure
www.youtube.com/watch?v=flv0RmzPyLU. There are several companies using patient’s own bone marrow as a source of stem cell therapy after manipulation, these include Aldagen, Baxter, Amorcyte, Micromet, and Harvest-Tech.

Unfortunately there is a problem with the bone marrow cells of patients with diabetes or other inflammatory conditions: the cells don’t work as well at making new blood vessels as compared to cells of healthy patients. One of the reasons for this is believed to be high concentrations of circulating TGF-beta in the blood of type 2 diabetics. This protein is known to suppress stem cell multiplication and is associated with the body trying to inhibit inflammation.

The study discussed in the paper Bhatwadekar et al. experimentally suppressed TGF-beta in CD34 cells from diabetic patients and asked whether this could restore the ability of the CD34 cells to generate new blood vessels.

The scientists used an artificially designed inhibitor technology called "morpholino antisense oligonucleotides" to treated CD34 cells. They demonstrated >90% suppression of TGF-beta production in the cells from diabetic patients. It was found that after inhibition of TGF-beta the ability of the CD34 cells to produce new blood vessels was substantially increased. This was demonstrated in the retinal ischemia reperfusion injury model in the mouse.

At a mechanistic level it appears that the therapeutic effects of TGF-beta inhibition were associated with increased ability to migrate to area of needed. This was demonstrated by higher expression of the receptor CXCR-4.

Filed Under: Diabetes, News Tagged With: , , , ,