August 27, 2010 by

Platelet-Rich Plasma Releasate Promotes Differentiation of Tendon Stem Cells Into Active Tenocytes.

(Zhang et al. Am J Sports Med. ) Platelet rich plasma (PRP) contains products of activated platelets which include numerous growth factors such as fibroblast growth factor, hepatocyte growth factor, insulin like growth factor, etc. Conventionally, PRP is used to promote various healing processes. In the area of sports medicine PRP has been used for the treatment of cartilage injuries and to accelerate their repair.

Given that numerous repair processes have been associated with stem cells, in the current study researchers sought to determine whether PRP may yield an effect on stem cell populations found in the joint called tendon stem cells (TSC).

The scientists found that treatment of TSC with PRP led to the cells taking on a large, well spread, and highly elongated shape. Furthermore, treatment with PRP results in a decrease of nucleostemin expression, which is associated with TSC activation. Treatment with PRP also enhanced TSC proliferation, tenocyte-related gene and protein expression, and total collagen production, all of which indicated that PRCR treatment induced differentiation of TSCs into activated tenocytes.

The possibility that PRP stimulates TSC may be examined in vivo in future experiments. For example, it would be interesting to see which of the many growth factors actually is responsible for the high proliferative response of the TSC.

One other area of interest is whether PRP may be used in absence of tissue culture media for stem cell expansion. Currently one of the major limiting factors in the area of cell therapeutics has been the lack of appropriate supply of fetal calf serum for en masse cell manufacturing. If the growth factors released by PRP are strong enough to stimulate cell proliferation in vitro, then this may be a solution to a big hurdle.

Filed Under: Adult Stem Cells, News, Stem Cell Research Tagged With: , , , ,
August 2, 2010 by

Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study.

Liang et al. Ann Rheum Dis. 2010 Aug;69(8):1423-9.

Mesenchymal stem cells are unique in that on the one hand they are capable of differentiating into a variety of tissues, but on the other hand they also are potently anti-inflammatory and immune modulatory.

Evidence of immune modulation comes from studies that show mesenchymal stem cells: a) directly suppress ongoing mixed lymphocyte reaction; b) produce immune suppressive cytokines such as IL-10; c) produce immune suppressive enzymes such as indolamine 2,3 deoxygenase; d) inhibit natural killer and CD8 cytotoxic T cell activity; e) inhibit dendritic cell maturation; and f) stimulate production of T regulatory cells.

Animal studies covered on our youtube channel www.youtube.com/cellmedicine have shown that mesenchymal stem cells inhibit collagen induced arthritis and experimental allergic encephalomyelitis, which represent human rheumatoid arthritis and multiple sclerosis, respectively.

Since these cells are such potent immune modulators, they have been used with some success in the treatment of immunological diseases such as graft versus host disease (GVHD). Medistem and Cellmedicine have previously used fat derived stem cells, which contain high concentrations of mesenchymal stem cells, in order to treat rheumatoid arthritis. In the current paper mesenchymal stem cells from the bone marrow where used to treat the autoimmune disease systemic lupus erythematosus.

Scientists at the Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, in Nanjing, China, reported a clinical trial of allogeneic (universal donor) mesenchymal stem cells in the treatment of patients with treatment-refractory systemic lupus erythematosus (SLE).

Fifteen patients with SLE who did not respond to conventional treatments where administered bone marrow derived mesenchymal stem cells isolated from allogeneic donors. No chemotherapy or immune suppression was used. Administration of stem cells was performed intravenously.

Mean patient follow up was 17.2+/-9.5 months with 13 patients have been followed for more than 12 months. 15/15 patients presented with clinical improvements subsequent to stem cell therapy. At 12-month follow-up, SLEDAI scores dropped from 12.2+/-3.3 to 3.2+/-2.8 and proteinuria decreased from 2505.0+/-1323.9 to 858.0+/-800.7 mg/24 h. At 1-year follow-up in 13 patients, 2 had a relapse of proteinuria, while the other 11 continue to have decreased disease activity on minimal treatment. Anti-dsDNA levels decreased. Improvement in glomerular filtration rate was noted in two patients in which formal testing was performed. Non-renal-related manifestations also improved significantly. No serious adverse events were reported.

This study demonstrated that mesenchymal stem cells are capable of not only inhibiting the pathological processes in SLE (eg production of anti-dsDNA antibodies) but also reversing renal damage that has occurred as a result of the disease process. The fact that some of the patients relapsed may mean that there is a rationale for multiple administration of mesenchymal stem cells.

Filed Under: Adult Stem Cells, Lupus, News, Stem Cell Research Tagged With: , , , , ,
August 1, 2010 by

Pluripotent stem cell-derived natural killer cells for cancer therapy.

Knorr et al. Transl Res. 2010 Sep;156(3):147-154. Epub

Immune therapy of cancer is an exciting prospect given the possibility of treating cancer without the side effects associated with conventional treatments such as chemotherapy or radiotherapy. Additionally, the use of the immune system to target tumors offers the possibility of eradicating micrometastasis, which often cannot be treated by conventional means.

Early work in the immunotherapy of cancer involved taking out patient lymphocytes that were infiltrating the tumor, expanding them outside of the body, and subsequently re-injecting them with the hope that expanded numbers of tumor-specific killer cells would destroy the tumor. Unfortunately this approach was very expensive and did not yield positive results to justify the complexity and expense of the procedure. One possible reason for the failure of this approach is that the cells used where already “old” and “exhausted”. In other words, previous encounters of the T cells with cancer antigens seems to have programmed them so as to inhibit ability to mount a proper immune response.

The use of natural killer cells as an alternative to T cells was considered. These cells, called lymphokine activated killers (LAK) displayed specific ability to kill tumors and were more effective than T cells alone. Unfortunately this approach too also required substantial manipulation of the cells outside of the body and was not practical.

In a recent paper, the group of Knorr et al discussed how to use stem cells to solve the problem of generating anti-cancer immune cells out of the body. They discuss how they have successfully used embryonic stem cells to generate “universal donor” natural killer cells. This approach is highly promising since NK cells do not need to be matched with the recipient in order to mediate anti-cancer activity. Additionally, since the cells are generated “brand new” in the laboratory, the problem of “exhaustion” is no longer relevant. Unfortunately there are still several obstacles to overcome such as the potential of embryonic stem cells forming leukemias/tumors, and the possibility of host anti-graft responses.

The paper also describes the future possibility of using inducible pluripotent stem (iPS) cells as a method of generating autologous T cells with any given TCR specificity.

Filed Under: Cancer, News, Stem Cell Research Tagged With: , , ,
July 31, 2010 by

Stem Cells for Spinal Cord Injury

The use of mesenchymal stem cells for a variety have
diseases has been published. This includes conditions such as heart failure,
liver failure, stroke, and lupus. One of the attractive features of mesenchymal
stem cells is that they can differentiate into numerous tissues while at the
same time exerting anti-inflammatory activities.

In the situation of spinal cord injury, mesenchymal stem
cells are thought to produce various growth factors that contribute to
regeneration of the damaged nerve. In the paper by Park et al the question was
asked whether Schwann Cells that are differentiated from mesenchymal stem cells
may be a more potent source of therapeutic growth factors. This question was
raised in part because the natural function of Schwann Cells is to produce
factors that accelerate new neuron formation.

The researchers used a growth factor-based differentiation
media to induce the transformation of mesenchymal stem cells into cells that
resemble Schwann Cells. The resulting cells developed a morphology similar to
Schwann Cells and expressed proteins that are specific to this cell type such as
the p75 neurotrophin receptor.

It was found that the Schwann Cells generated from the
mesenchymal stem cells expressed higher amounts of the growth factors hepatocyte
growth factor (HGF) and vascular endothelial growth factor (VEGF) when compared
with non transformed mesenchymal stem cells. When the newly generated cells
were cultured with a neuronal cell line called Neuro2A, a large increase in the
proliferation of the cell line was noted with a decrease in spontaneous cell
death. Transplantation of the artificially generated Schwann Cells into an ex
vivo model of spinal cord injury dramatically enhanced axonal outgrowth. This
was blocked by antibodies to HGF and VEGF.

The authors propose that artificially generated Schwann
Cells without genetic modification are useful for autologous cell therapy to
treat nervous system injury.

One
important question that was not addressed is to what extent are the Schwann
Cells generated from mesenchymal stem cells seen by the immune system. In other
words, is it possible to use Schwann Cells in a universal donor fashion the same
way that mesenchymal stem cells can be used.

Filed Under: Adult Stem Cells, News, Spinal Cord Injury, Stem Cell Research Tagged With: , , , ,
July 29, 2010 by

Protein Found on Endometrial Regenerative Cells Inhibits Immune Attack

Medistem Inc. (PINKSHEETS: MEDS) announced today publication of a peer reviewed paper identifying a molecule found on the company’s lead product, the universal donor Endometrial Regenerative Cell (ERC), as a key component of cellular escape from immune attack. The study, entitled “Resistance of neonatal porcine Sertoli cells to human xenoantibody and complement-mediated lysis is associated with low expression of alpha-Gal and high production of clusterin and CD59” was published in the journal Xenotransplantation as a collaboration between Medistem and the Institute of Organ Transplantation, Tongji Hospital, in Wuhan, China.

The study found that CD59, a molecule made by ERC, plays an important role in protecting cells from immune rejection when placed in contact with immune components from another species. The ERC is a mesenchymal-like stem cell that Medistem discovered in 2007 capable of generating heart, lung, brain, muscle, blood vessel, pancreas, liver, fat and bone tissue. The original description of this cell, which won the “Publication of the Year Award” may be found at http://www.translational-medicine.com/content/pdf/1479-5876-5-57.pdf.

“One of the fundamental aspects of Medistem’s lead product, the Endometrial Regenerative Cell (ERC), is its ability to function without the need for tissue matching. In other words, the ERC stem cells act as universal donors. We have previously published that human ERC are effective in treating mice having a condition that resembles critical limb ischemia (see paper http://www.translational-medicine.com/content/pdf/1479-5876-6-45.pdf ). We now believe that expression of the molecule CD59 on ERC may be one of the mechanisms by which these human cells can be used not only as a universal donor for humans, but also for the treatment of numerous diseases across a variety of animal species.” Said Thomas Ichim, CEO of Medistem.

Medistem has filed an IND with the FDA for treatment of critical limb ischemia (severe obstruction of the arteries that leads to decreased blood flow to the extremities) with ERC. Currently the company is in the process of completing additional experiments requested by the FDA before clinical trials can commence. Through physician-initiated compassionate use mechanisms Medistem has already published on human use of ERC in treatment of heart failure, Duchenne Muscular Dystrophy, and multiple sclerosis. A recent peer-reviewed paper describing ERC in treatment of heart failure may be found at http://www.intarchmed.com/content/pdf/1755-7682-3-5.pdf.

Filed Under: Adult Stem Cells, Endometrial Stem Cells, News, Stem Cell Research Tagged With: , ,
July 2, 2010 by

Eradication of brain tumor stem cells with an oncolytic adenovirus.

Jiang et al. Discov Med. 2010 Jul;10(50):24-8.

Philosophically, tumor cells have an advantage to humans in the “War on Cancer”. That is, the tumors have the ability to rapidly mutate, so that when drugs are given to fight the tumor, the tumor can “mutate around” the drug and become resistant. This occurs in several ways: a) the tumor starts expressing drug efflux pumps, such as the multi-drug resistance (MDR) protein that actively transports chemotherapeutics out of cancer cells; b) the tumor mutates the kinase or molecular target that the drug is inhibiting; and c) the tumor increases expression of other oncogenes that are not inhibited by the drug.

One interesting method of dealing with the problem of tumor mutation is to use agents against the tumor that are actively mutating. One approach has been the use of viruses that have a selective ability to infect tumors and to kill them. These are called “oncolytic” viruses. One of the most well-known oncolytic virus is the Reovirus, which only replicates in cells that express high concentrations of the oncogene RAS. This virus is in clinical trials by the Canadian company Oncolytics.

Delta-24-RGD is an oncolytic adenovirus that is capable of infecting glioma cells and preferentially inducing their death. It is being developed at the Brain Tumor Center, The University of Texas MD Anderson Cancer Center and is the subject of an ongoing Phase I clinical trial in the treatment of patients with therapy-resistant glioma.

One of the key issues surrounding any cancer therapeutic is whether the treatment is targeting tumor stem cells, or only the tumor progeny cells. This is very important because tumor stem cells are usually resistant to chemotherapy or other interventions that require cells to be metabolically-active and hyperproliferating. The majority of tumor cells are metabolically-active and fast multiplying, these cells are usually destroyed by conventional drug approaches, however, subsequent to their destruction the tumor stem cells exit quiescence and start making a new tumor. This has been one of the primary reasons for the poor success rate of cancer therapeutics that are currently under development.

In the current paper scientists found that the Delta-24-RGD virus is capable of infecting and causing death of glioma stem cells. This is a very important finding because it implies the possibility of attaining tumor cure by administration of such an oncolytic virus. Other advantages of the oncolytic virus approach is that the process of tumor cell death likely releases numerous antigens which cause activation of systemic immunity towards micrometastasis. Unfortunately one of the drawbacks of cancer therapy using oncolytic viruses is that the host develops an immune response to the virus which does not allow for long term continual administration. Patients interested in this treatment should contact Dr. Jiang at hjiang@mdanderson.org .

Filed Under: News, Stem Cell Research Tagged With: , , , , ,
June 28, 2010 by

Arthritis Patient Successfully Treated With Fat Stem Cells Tells His Story

This procedure has been used successfully to treat thousands of animals suffering from arthritis in the United States (www.vet-stem.com). Recently Dr. Paz published a paper describing scientific mechanisms of this treatment in collaboration with scientists from the University of California San Diego, University of Western Ontario, and Medistem Inc (Ichim et al. Autologous stromal vascular fraction cells: A tool for facilitating tolerance in rheumatic disease. Cell Immunol. 2010 Apr 8).

“I had treatment for my arthritis, I was not wheelchair bound but I was getting there… after stem cell treatment my arthritis symptoms disappeared,” stated Mr. Durrill.

More than 200 people attended the lecture including the general public, patients and medical doctors. The lecture was focused on US and European clinical trials supporting the use of adult stem cells in conditions ranging from multiple sclerosis, to heart failure, to diabetes. A video of part of the lecture is available at www.kiiitv.com.

Dr. Paz commented, “Mr. Durrill suffered from arthritis for more than ten years with severe pain in both knees and hips. He had difficulty standing and limited mobility. After stem cell therapy he started showing significant reduction in pain. Now about a month after therapy he is pain free and can move around easily.”
Drs. Robert Harman, CEO of Vet-Stem and Thomas Ichim, CEO of Medistem, recently released a video discussing their publication on fat stem cell therapy for arthritis. The video is available at www.youtube.com.

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. A publication describing the support for use of ERC for this condition may be found at www.translational-medicine.com.

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.

Filed Under: News Tagged With: , , ,
June 21, 2010 by

Medistem Reports Rheumatoid Arthritis Patient Success Using Adult Stem Cell Protocol

SAN DIEGO, CA – (Marketwire – June 21, 2010) – Medistem Inc. Medistem Inc. together with the Stem Cell Institute reported today publication in the peer reviewed journal Cellular Immunology its paper titled “Autologous stromal vascular fraction cells: A tool for facilitating tolerance in rheumatic disease,” which describes the first use of a patient’s own fat stem cells for treatment of rheumatoid arthritis.

How Fat Stem Cells May Work on Autoimmune Diseases

In collaboration with the company Vet-Stem Inc, the University of Western Ontario, and The University of California San Diego, Medistem scientists detailed the scientific rationale for use of patient’s own fat derived stem cells for “reprogramming” the immune system of patients with autoimmune diseases such as rheumatoid arthritis. A case report of a 67-year-old American woman who recovered from rheumatoid arthritis after intravenous treatment with adult stem cells is provided.

“We have been treating companion animals for osteoarthritis and rheumatoid arthritis for over five years, achieving and publishing excellent efficacy data,” said Robert Harman, CEO of Vet-Stem. “Medistem’s identification of potential mechanisms of action, as well as translation of this technology into the clinic, supports the importance of our findings.”
Medistem previously identified and filed intellectual property covering the co-purification of high concentrations of T regulatory cells using protocols that enrich for adipose derived stem cells, a finding that was later confirmed and published by Diane Mathis’s group from Harvard University (Feuerer et al. Nat Med. 2009 Aug;15(8):930-9). T regulatory cells are used by the body to control autoimmunity, which is explained in this video by Thomas Ichim, the CEO of Medistem.

“We are very excited that Medistem’s protocol for isolation of a patient’s own fat derived stem cells and T regulatory cells, which produced promising results in multiple sclerosis, appears to be useful in rheumatoid arthritis, another autoimmune disease,” said Neil Riordan, Chairman of Medistem.

In a 2009 paper Medistem together with Vet-Stem and University of California San Diego reported substantial clinical improvement in a small group of multiple sclerosis patients treated using a similar protocol. The paper is available at www.translational-medicine.com.

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. A publication describing the support for use of ERC for this condition may be found at www.translational-medicine.com.

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.

Filed Under: Adult Stem Cells, News, Rheumatoid Arthritis, Stem Cell Research, Stem Cell Therapy Tagged With: , , ,
June 7, 2010 by

Statement From The Stem Cell Institute Regarding Decision to Close Costa Rican Operations

The Stem Cell Institute announced today that it proactively and independently made the business decision in early June to close its clinic and lab in Costa Rica and centralize all operations in Panama City, Panama. This decision was made voluntarily.

This decision, which came after careful consideration, was reached in response to Costa Rica’s unpredictable and arbitrary regulatory landscape. During its time in Costa Rica the company operated in full compliance with all existing laws and regulations. Unfortunately, however, the recent lack of clarity regarding adult stem cell treatment regulation in Costa Rica proved to be too great a risk for The Stem Cell Institute to continue its work in that country.

The Stem Cell Institute maintains the highest standards of ethics, transparency and consistency. Its adult stem cell therapy treatments are conducted with the strictest adherence to legal, ethical and industry guidelines. All cells used in treatments are processed in accordance with Current Good Tissue Practices (cGTP) in a state-of-the-art laboratory that is fully licensed and certified. Our staff is comprised of highly trained doctors and other medical specialists who have dedicated years to uncovering new treatments to aid those challenged by chronic diseases for which there are inadequate standard therapies.

The company came to this decision with much regret and will dearly miss its colleagues, patients and friends in Costa Rica. In just four years, The Stem Cell Institute helped hundreds of people who are challenged with chronic diseases such as Cerebral Palsy, Multiple Sclerosis, Osteoarthritis, Rheumatoid Arthritis, Muscular Dystrophy, and Spinal Cord Injury.

The company’s commitment to helping patients with chronic diseases benefit from new, cutting edge adult stem cell therapies is unchanged. It has a vibrant, growing clinic in Panama City that has already served more than 150 since opening in 2007. The government of Panama has clearly-defined laws that regulate adult stem cell therapies. Moreover, Panama City is an easily accessible metropolitan city with world-class facilities and accommodations to better serve our patients. The Stem Cell Institute’s facilities in Panama are fully licensed and certified.

Filed Under: News Tagged With: , , , ,
May 20, 2010 by

Pluristem’s Off-The-Shelf Placenta-Derived Cell Therapies

Pluristem announced that its "off the shelf" placental stem
cells will be the focus of upcoming talking at investor and medical
conferences. The company Pluristem is currently in Phase I trials assessing its
unique bio-reactor expanded placental stem cells for the treatment of critical
limb ischemia. In contrast to other therapies that use the patient’s own stem
cells (called autologous), the advantage of the "universal donor" or
"allogeneic" approach is that large numbers of cells can be generated according
to defined conditions. Additionally, universal donor cells can be administered
several times at a number that is limited only by the desire of the physician to
escalate the dose. In the autologous situation stem cells are usually taken
from the bone marrow, making it difficult to perform multiple extractions.

Pluristem will present at the International Society for
Cellular Therapy’s (ISCT) 16th Annual Meeting in Philadelphia some updates on
its ongoing programs.

"We recently reported interim top-line results from our
Phase I clinical trials demonstrating that PLX-PAD is safe, well tolerated and
had improved the quality of life of CLI patients in the studies," said Zami
Aberman, Pluristem’s chairman and CEO. "With PLX-PAD, we have the unique
opportunity to utilize a single source of cells, the placenta, to treat an
unlimited number of CLI patients. Our presentations at the ISCT Annual Meeting
and other conferences will highlight the potential of PLX-PAD as well as our
core technology that enables the cost-effective development of cell therapies
derived from the human placenta."

There are several other companies pursuing "universal
donor" stem cells. Medistem, the licensor of technologies used by Cellmedicine
has developed such a cell from the endometrium, called "Endometrial Regenerative
Cells" that are currently subject of an IND application for use in critical limb
ischemia. Athersys is using bone marrow derived universal donor stem cells for
treatment of heart failure. The most advancement in this area comes from the
company Osiris Therapeutics which also uses bone marrow derived cells to treat a
variety of conditions, although all are still in clinical trials.

In
the majority of cases universal donor cells are related directly or indirectly
to mesenchymal stem cells. These cells, originally discovered by Dr. Arnold
Caplan, express low levels of proteins that are seen by the immune system, thus
allowing them to be transplanted without matching. Additionally, they also
produce proteins that actively suppress the immune system from killing them. In
diseases associated with abnormal immunity mesenchymal stem cells have shown
promise. Cellmedicine has published on use of mesenchymal stem cells in
treatment of multiple sclerosis

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