In part 6, Prof. Caplan discusses Trophic properties of mesenchymal stem cells; MSCs for heart disease; MSCs homing to heart injury site and also to skin incision site; MSCs limit left ventricular thinning following infarction; Trophic properties of MSCs: anti-apoptotic, anti-fibrotic, anti-scarring, angiogenic, mitotic; phase 1 data for allogeneic MSCs show fewer arrhythmias, prompt heart rate recovery, and improved lung function; autologous adipose tissue-derived stromal vascular fraction for treatment of chronic heart disease; Active mesenchymal stem cell clinical trials around the world; Induction therapy with autologous MSCs in kidney transplants; MSCs can coax neural stem cells to become oligodendrocytes, curing mice with MS using allogeneic human MSCs.
VIDEO – The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (Part 6)
Medistem Inc. to Add Kidney and Lung Failure to Clinical Trials of Endometrial Regenerative Cells (ERC) Stem Cells in Russia
SAN DIEGO, CA and PORTLAND, OR, Mar 05, 2012 (MARKETWIRE via COMTEX) — Medistem Inc. (pinksheets:MEDS), in partnership with its Russian licensee, ERCell, announced the signing of a letter of intent* to begin clinical trials using Medistem’s Endometrial Regenerative Cells (ERC) stem cells for renal, lung and peripheral artery disease. Trials will be conducted in the S.M. Kirov Military Medical Academy in St. Petersburg, Russia. Under the agreement, Medistem, ERCell and the Academy will work together to a) Design and obtain approval for clinical trials; b) Provide training and execute the trials; and c) Identify opportunities for commercialization of the ERC product through existing military and governmental programs.
Under the license agreement, Medistem receives cash and royalty revenues from Russian developmental activities as well as all the data gathered from the trials. According to the agreement, work performed by ERCell will be conducted according to international “Good Clinical Practices” (GCP) so the data gathered can be used for Russian registration as well as to support US FDA submissions.
“At Medistem, our philosophy has always been to follow the data. We aim to be as aggressive as possible, to obtain as much data as possible, as quickly as possible,” stated Thomas Ichim, CEO of Medistem. “We are especially optimistic about the possibility of obtaining human data in renal failure patients, something that we otherwise would not have pursued at this stage if it weren’t for the support of the S.M. Kirov Military Medical Academy.”
“As the Medistem licensee for Russia and CIS (Commonwealth of Independent States), ERCell is committed to advancing our programs using as many non-dilutive means as possible,” said Tereza Ustimova, CEO of ERCell. “By partnering with the best institutes in the country, we are committed to making ERCell Russia’s premiere universal donor adult stem cell company.”
S.M. Kirov Military Medical Academy conducts research in the following areas: metabolic derangements of cardiovascular pathology, nanotechnologies in biology and medicine, stem cells as a basis for the treatment of internal organs and blood diseases, blood circulation, vegetative nervous system and high-tech methods of diagnosis and treatment.
“We are highly impressed by the fact that the Endometrial Regenerative Cell (ERC) is the newest stem cell product to enter clinical trials. By the higher growth factor production ability compared to other types of stem cells, we are very eager to begin clinical trials,” said Oleg Nagobovich, M.D., Chief of the Research Center, S.M. Kirov Medical Military Academy. “We feel our work will complement the ongoing work at the Backulev Center addressing heart failure by Medistem/ERCell.”
*Letter of intent issued by Ministry of Defense, dated 2/24/12, No. 411A/119
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 http://www.translational-medicine.com/content/pdf/1479-5876-6-45.pdf . ERC can be purchased for scientific use through Medistem’s collaborator, General Biotechnology http://www.gnrlbiotech.com/?page=catalog_endometrial_regenerative_cells .
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
858 642 0027
www.medisteminc.com twitter: @thomasichim
SOURCE: Medistem Inc.
Bone Marrow Stem Cells Protect Lungs from Herbicide Injury
Yang et al. Clin Toxicol (Phila). 2011 Apr;49(4):298-302.
Paraquat is a herbicide that is linked to development of Parkinsons. It also is a toxin to lung cells and is used as a model of inducing lung injury in rats. In the current study the investigators wanted to see if administration of bone marrow mesenchymal stem cells had a therapeutic effect on paraquat-induced lung injury in rats.
The investigators used 54 female SD rats that were randomly divided into four groups:
a) Paraquat treated group,
b) Paraquat and bone marrow mesenchymal stem cell treated group,
c) Bone marrow mesenchymal stem cell alone treated group
d) Control untreated group
The stem cells were injected intravenously and animals were sacrificed 14 days after injection.
While animals receiving paraquat alone lived an averaty of 9.6 days, all rats receiving bone marrow mesenchymal stem cells lived more than 14 days. Bone marrow mesenchymal stem cell treatment was associated with less wet lung, decreases in plasma IL-1 and TNF-alpha, decrease in MDA, and decrease in NF-kappa B. Upregulated levels of the antioxidant enzyme superoxide dismutase was observed.
The ability to stimulate repair of the lung by mesenchymal stem cells is not new. Previous studies have shown that mesenchymal stem cells are capable of reducing endotoxin induced lung injury by secretion of keratinocyte growth factor. Other studies have shown that mesenchymal stem cells produce interleukin 1 receptor antagonist in the bleomycine induced model of lung fibrosis.
As with other stem cell therapies described on this website, there is some controversy as to the biological mechanisms by which the stem cells are mediating their therapeutic effect. One possibility is that they are secreting growth factors that stimulate proliferation of endogenous stem cells that are already resident in the lung. The other possibility is that the stem cells are directly differentiating into lung tissue.
Stem Cells Restore Tissue Affected By Acute Lung Injury
Researchers from the University of California San Francisco
presented data today at the ATS 2010 International Conference in New Orleans
demonstrating activity of adult stem cells in treatment of acute lung injury.
This is a common condition in intensive care units that causes respiratory
failure and often leads to death. The cause of acute lung injury is usually
blood borne bacterial infections (sepsis), major trauma, aspiration, or direct
infection of the lung in situations like pneumonia or severe viral infections.
Acute lung injury has a 40% mortality rate and strikes an average of 200,000
patients in the US a year.
In order to study the effects of stem cells in this
condition, human lungs that were not suitable for transplantation were pumped
with blood outside of the body and administered endotoxin, a component from
bacterial walls that causes lung failure in patients with sepsis.
The researchers demonstrated that bone marrow derived
mesenchymal stem cells where capable of preserving lung function and inhibiting
the inflammation when administered to the human lung. Perhaps most important
was the finding that water did not leak into the lung, which is one of the major
causes of respiratory impairment.
"We found that intravenous infusion of clinical grade cryo-preserved
allogeneic hMSC were effective in restoring the capacity of the alveolar
epithelium to resolve pulmonary edema when given after the establishment of E.
coli endotoxin-induced acute lung injury in an ex vivo perfused human lung
preparation," explained Jae-Woo Lee, M.D., who led the study in the laboratory
of Michael A. Matthay, M.D. "In addition, we found that intravenous infusion of
hMSC preferentially homed to the injured areas of the lung, which means that the
cells find their way from the bloodstream to the sites in the lung of injury."
This findings are of particular interest because stem cells
are usually used in the treatment of chronic conditions in which the
administered cells are accelerating/augmenting healing processes that usually
take weeks if not months. In contrast, the therapeutic effects of stem cells in
the context of acute lung injury occur in a matter of hours.
Previously the same research group administered adult stem
cells into the bronchioles of the lung and demonstrate therapeutic effects. The
possibility of injecting stem cells intravenously would possess several
advantages in the treatment of patients that are critically ill, this is because
these patients are usually under mechanical ventilation and the bronchoscopy
procedure may lead to complications.
"These results suggest that the intravenous route would be
ideal for potential clinical trials of hMSC for severe acute lung injury, a
syndrome of acute respiratory failure in critically ill patients that is
associated with 40 percent mortality," said Dr. Lee.
He continued "These results extend our recent publication,
which demonstrated that hMSC may have therapeutic potential clinically in
patients with severe acute lung injury. We need to do more experiments with
testing the effect of hMSC against live bacterial induced lung injury in the
perfused human lung and now advance to doing Phase I and II safety and efficacy
studies in patients."
In
their previous publication the group demonstrated that mesenchymal stem cells
produce the protein keratinocyte growth factor (KGF)-1 which is responsible in
large part for maintaining integrity of the lung. Additionally, they
demonstrated that even administration of proteins made by the mesenchymal stem
cells, without mesenchymal stem cells being in the mix, would also elicit
therapeutic effects.
Ahmedabad-based institutes get patent to use stem cells in kidney transplant
According to an article IndianExpress.com, an international
patent has been issued to the G R Doshi K M Mehta Institute of Kidney Diseases
and Research Centre (IKDRC) and Dr HL Trivedi Institute of Transplantation
Sciences (ITS) from Ahmedabad, Indian for utilization of stem cells in treatment
of patients having undergone kidney transplantation. Given that we could not
find a patent number written in the article, as well as the fact that
"International Patents" do not exist, we presume the authors meant a provisional
patent having international priority under Paris Convention, or a Patent
Cooperation Treaty (PCT) application.
The subject matter discussed is the use of stem cells to
circumvent the need for immune suppression during transplantation. While immune
suppressants such as cyclosporine, rapamycin, and FK-506 have saved many lives
by making transplantation possible, they have numerous side effects associated
with their long-term use. These include increased risk of cancer, higher number
of bacterial/viral infections, and possibility of kidney failure. The work
discussed in the article uses the ability of stem cells to "immune modulate" and
therefore inhibit rejection. A video describing stem cell mediated immune
modulation may be seen at this link
http://www.youtube.com/watch?v=ECi2uBSSQg8.
Dr Aruna Vanikar, Head of Pathology, Lab Medicine,
Transfusion Services and Immuno hematology department, IKDRC-ITS, who according
to the article recently received the patent, stated, "We have been working on
the use of stem cells since 1998. The study involved several phases. When a
patient undergoes kidney transplant, he/she might face difficulties, including
complete rejection. To suppress that, several drugs are used…Sometimes, the body
also reacts to high dosage of drugs. With this patent, patients will not have
any such complications. The stem cells would comprise mesenchymal cells
generated from the donors’ fat, and haematopoetic stem cells taken from donors’
bone marrow and blood. These cells are infused in the recipients’ liver, as it
is considered the most tolerogenic organ of the body."
While the article did not provide technical details, we
found on
www.pubmed.com some of Dr. Vanikar’s work. A recent publication: Effect of
co-transplantation of mesenchymal stem cells and hematopoietic stem cells as
compared to hematopoietic stem cell transplantation alone in renal
transplantation to achieve donor hypo-responsiveness. In the journal Jan 19th
edition of the International Urology and Nephrology Journal described the
reduction of immune suppressant dosage by administration of bone marrow and fat
derived stem cells. Another paper from the same group described the reduction
of immune suppressant dose by a similar stem cell protocol, termed the
"Ahmedabad tolerance induction protocol". It will be interesting to see if
these early clinical results can be translated into Phase III placebo controlled
trials. Commenting on the "tolerance induction protocol" Dr Aruna Vanikar said:
"With modification in Ahmedabad tolerance induction protocols for
transplantation without conventional immunosuppression, the results are
rewarding. Secondly, the incidences of acute and chronic rejection and
recurrence of basic disease have decreased."
