Stem Cell Research

Stem Cell Solutions: Endothelial Stem Cells, Suggested Source Of Stem Cell Therapies, Not Always What They Seem

In a result that has implications for future clinical trials, researchers have found that conventional methods for isolating mononuclear cells from blood in order to grow endothelial progenitor cells (EPCs) do not result in a pure cell sample.  Turns out they can be contaminated with markers from platelets.

Endothelial progenitor cells are a type of stem cell that have been studied for the past decade. They originate in the bone marrow and circulate in the blood. When they receive the correct signals, they are able to develop into endothelial cells, which form the lining of our blood vessels. EPCs have been suggested as a source of stem cell-based therapies to contribute to the repair of heart tissue.

Dr Manuel Mayr, from the Cardiovascular Research Division at King’s College London was aided by his research team at the College's British Heart Foundation Center of Research (BHF).  The team collected blood samples from human volunteers then isolated mononuclear cells in order to grow EPCs. They then used proteomics to examine the characteristics of these cells.

"Surprisingly, we found that conventional isolation methods used by scientists and doctors do not result in a pure cell sample," said Mayr, "because they are also contaminated with markers from another type of blood cell called platelets."

Induced Pluripotent Stem Cells Repair Heart In Mayo Clinic Study

A great deal of work is being done to come up with a method of reverting adult stem cells to an embryonic-like state without making them inherently dangerous in the process. Of course after the adult cells are returned to an embryonic-like state they have to be coaxed into becoming the type of cell that is necessary in the particular regenerative medicine application.

About a month ago a Mayo Clinic study, one that delivered embryonic stem cells to mouse embryos in the earliest stages of development, found that the resulting mice demonstrated a capacity to recover from cardiac injury in adulthood.  According to Mayo this study provides the first evidence that preventive regenerative medicine can successfully be used to treat myocardial infarction through prophylactic intervention.

Mayo researchers injected mouse embryos with embryonic stem cells that had been used to successfully treat ischemic heart disease following heart attack. The resulting animals incorporated between five and 20 percent of labeled stem cell-derived tissue. They were born with no apparent abnormalities, and the tested and control groups had similar overall baseline cardiac disease risk profiles. They also demonstrated similar cardiac performance during the one year follow-up.

Now, In a proof-of-concept study, Mayo researchers have demonstrated that induced pluripotent stem (iPS) cells can be used to treat heart disease. In this study, researchers reprogrammed ordinary fibroblasts, cells that contribute to scars such as those resulting from a heart attack, converting them into stem cells that fix heart damage caused by infarction.

Medicine's New Toolbox: MIT's View Of Induced Pluripotency's Future

"The past two years have been nothing short of a revolution," says John Dimos, a senior scientist at iZumi Bio. "These cells didn't really exist two years ago. This is all brand-new technology, and it's opening up the potential for brand-new science." The company John is with, Izumi Bio, plans to take advantage of that potential by developing a bank of iPS cells from patients with various diseases and using the cells to screen candidates for drug development.

As a postdoc at Harvard, John Dimos built a cellular model of ALS (amyotrophic lateral sclerosis - Lou Gherig's Disease), making it possible to study a neurodegenerative disease outside an animal for the first time. He and his colleagues collected skin cells from an 82-year-old woman with ALS, reprogrammed them into iPS cells, and directed the cells to differentiate into motor neurons that were genetically identical to the donor's defective cells. "It was the first paper to show that you can use a stem cell to see disease pathology in a petri dish," says Douglas Melton, codirector of the Harvard Stem Cell Institute. "That means you can now study diseases in petri dishes and not in people. That's huge."

Pluristem Therapeutics Receives European Regulatory Approval for Placental-Derived Stem Cell Clinical Trial

A recent study by Children's Hospital Oakland suggests the placenta contains the same quality stem cells as cord blood but in much larger numbers.  The primary problem with cord blood has been the relatively small harvest of stem cells for use in transplants. 

Pluristem Therapeutics, one of our Sector Companies, specializes in therapies derived using placental derived stem cells.  Now, the European Union, has approved the Company’s Clinical Trial Application (CTA) and granted approval to begin clinical trials with its placental-derived adherent stromal cell product, termed PLX-PAD, for the treatment of critical limb ischemia (CLI), the end-stage of peripheral artery disease (PAD). In addition, Pluristem has already received approval from the Ethics Committee and, as previously announced, the US Food & Drug Administration (FDA) had cleared the Company’s Investigational New Drug (IND) application to initiate a similar trial in the United States. Both approvals of the CTA and IND clear the way for the world’s “first-in-man” clinical trial using PLX-PAD.

Pluristem’s placental-derived stem cells are expanded using the company’s proprietary 3D PluriX™ technology. PLX-PAD is an off-the-shelf, one-size-fits-all product that needs no tissue matching prior to being administered to patients. In these phase I trials, to be conducted at multiple locations in the US and Germany, PLX-PAD will be administered to patients considered "late stage" that have not responded to traditional medical or surgical interventions.

In the US alone, it is estimated that 8-12 million people suffer from critical limb ischemia associated with PAD. Several Sector Companies are researching and testing applications for critical limb ischemia.

Adapted from the Pluristem Therapeutics announcement.

Perspectives On The Cytori Therapeutics Cardiovascular Preclinical Study: Use Of Adipose Stem Cells In Heart Attack Model

Press releases from Stem Cell Sector Companies serve the purpose of raising awareness in both the medical and investing communities.  Stem Cell research, the development of regenerative medicine, and the evolution of commercialized applications are all moving forward.  As with any human endeavor, the forward moves are not always smooth.  Sometimes commercialized applications can actually precede research results.  Such has been the case with our Sector Companies that manufacture and sell medical devices. 

Cardiogenesis, Athersys, Thermogenesis, Bioheart, Cytori Therapeutics, are all companies hoping that research and eventual clinical test results will make the devices they manufacture more in demand in the medical market place.  At times what information is released to the press is expressed in ways to suggest greater results are at hand than might actually be the case.  For the investing public, these announcements always pose a challenge.  Reported results or advances must be placed in a context, something not always easy to do.

Most recently, on May 28th, Cytori Therapeutics (CYTX) issued a press release titled, "Cytori Reports Publication of Cardiovascular Preclinical Study; Adipose Stem & Regenerative Cells Improve Function in Heart Attack Model."

Scientists Identify Key Factors in Heart Cell Creation

For the first time key genetic factors that drive the process of generating new heart cells have been identified by Benoit Bruneau, Ph.D. and his research team at the Gladstone Institute. The team found that a combination of three genes could do the trick. This is the first time any combination of factors has been found to activate cardiac differentiation in mammalian cells or tissues.

"The heart has very little regenerative capacity after it has been damaged," said Dr. Bruneau. "With heart disease the leading cause of death in the Western world, this is a significant first step in understanding how we might create new cells to repair a damaged heart."

Bioheart, Inc. And Cytori Therapeutics: The Difference Is In The Business Plan

Bioheart, Inc. and Cytori Therapeutics are included in our small cap sector companies.  Both extract and create a broth of stem and other autologus, adipose derived, regenerative cells (here, as in the medical devices the companies are relying upon, there are proprietary differences) which can be reintroduced to the patient for therapeutic use.  While Cytori (perhaps because of its early partnership with Olympus) has pressed for regulatory approval and market introduction in Europe and Japan, Bioheart has been attempting to gain approvals in the U.S. and European markets.  Bioheart has a market value of 11 million; Cytori's market value is 111 million.

Tests of Novel Stem Cells Show Robust Repair of Injured Heart Muscle

The various physical maladies that affect the human heart are the subject of a great deal of stem cell research.  Several of our sector companies are trying therapies using a variety of stem cells from a variety of sources.  The race is on to see which works best.  But, at this stage, no one is even sure exactly what it is the stem cells are doing when they arrive in the vicinity of the damage they are sent to repair,  That said, improvement has been shown for several types of damage.  Not the perfect cure as yet, but definitely improved function.

The latest candidate stem cells are called myoendothelial cells, so named by Johnny Huard and Bruno Péault at the University of Pittsburgh's McGowan Institute for Regenerative Medicine.  Adult human muscle tissue harbors a population of these unusual progenitor cells that can regenerate skeletal muscle more effectively than other known muscle progenitor cells.

Osiris And The First Stem Cell Research FDA Breakthrough

The day one of our stem cell sector companies gains FDA approval for a directly applied therapy the result may well be the same for stem cells as that famous day in 1906 was for football. Saint Louis University's Bradbury Robinson tossed the first forward pass to teammate Jack Schneider and created the modern game. For stem cells that day may not be far away.  Our money is on Osiris Therapeutics to be the first to gain FDA approval. Osiris's Prochymal has a good chance to be the stem cell arena's first forward pass.

Cord Blood Stem Cells Grown Into Heart Valves

According to the March of Dimes, heart defects are among the most common birth defects and are the leading cause of birth-related deaths. In the United States alone, about 35,000 infants (1 out of every 125) are born each year with heart defects. Among the most common congenital heart problems are heart valve defects, where the heart valve either does not close normally or is narrowed or blocked, so blood can’t flow smoothly.

Now, German scientists are hopeful that within five to seven years, they will be able to fashion a new heart valve for children born with heart valve defects that would grow as the child develops using stem cells collected at birth from the child’s own umbilical cord blood. 

Primary Differentiation Gene Found For Heart Repair From Stem Cells

The gene that locks mouse embryonic stem cells into becoming heart parts and navigates them to the area where the heart forms has been isolated by scientists at Washington University School of Medicine in St. Louis. Researchers are now trying to determine whether stem cells exposed to this gene (known as Mesp1) can help fix damaged mouse hearts.

"Finding out how to program an embryonic stem cell to, say, create or repair a human heart, is like playing a Mozart requiem on a piano with 5,000 keys when you have no music and have never heard the sound."  I don't remember who said that, but whomever it was should get the blue ribbon for embryonic stem cell research metaphor.  It pretty well encapsulates the difficulty in determining the process by which an embryonic stem cell differentiates into a cell with a particular function in the body.

Heart: Skin Cells Reprogrammed Into Functioning Heart Cells

UCLA researchers have differentiated stem cells induced from adult mouse skin cells into the three types of cardiovascular cells necessary to repair heart and blood vessels.  The next step for Dr. Robb MacLellan's team will be an attempt to recreate the same process with human cells.

This work is important because embryonic stem cells injected directly into the heart in animal models create tumors in many cases.  Why? Because the cells differentiate not only into cardiac cells but into other cells found in the human body as well, including cancer cells.

Heart: Fully Functioning Heart Cells Grown From Heart Stem Cells

    "We've got complete control of this process, and that's unique," said principal investigator Prof. Pieter Doevendans.  "We're able to make heart muscle cells in unprecedented quantities.  On top of that, The laboratory grown heart cells are all the same.  This is good news in terms of treatment, as well as for scientific research and testing of potentially new drugs."

    Using material left after open-heart operations, researchers at University Medical Center Utrecht and the Hubrecht Institute have isolated heart stem cells and reproduced them without a growth medium that includes other heart muscle cells such as from newborn mice.  The cells grow into fully developed heart muscle cells that contract rhythmically, respond to electrical activity, and react to adrenaline.

    Using this technique, stem cells from the hearts of patients with genetic heart defects can be grown into heart muscle cells in the lab and studied to find out what causes the condition.  Lab grown heart muscle cells can also be used to test new drugs which could speed the pace of development and transition into clinical trials.

    Read the entire UMC Utrecht announcement here.  Comments?

   

Heart Disease: Drug Treated Stem Cells Repair Heart Damage

    Researchers at the UT Southwestern Medical Center have accomplished a first.  They've used drug-treated blood stem cells to repair heart damage in a mouse.  To do it they had to screen 147,000 molecules to find one that could transform human blood stem cells into a form resembling immature heart cells. 

    "The clinical potential is enormous," said Dr. Jay Schneider, assistant professor of internal medicine and senior author of the study. "Despite medical advances in treating and preventing heart attacks, once the heart is damaged it cannot repair itself."

Heart Disease: Can Stem Cells Improve Circulation in Damaged Coronary Arteries?

    The Massachusetts General Hospital Heart Center plans to find out. Blockage of the coronary arteries leading to the heart due to cholesterol plaque and blood clots impairs blood flow and oxygen supply. We're all aware of the resulting heart disease, chest pain, heart attacks and even sudden death that can occur.

    The MGH trial is to determine whether a patient's autologous (patient's own) stem cells can improve circulation in a heart damaged by inadequate blood flow resulting in life extension and improved quality of life.  Doulas Drachman, MD, an interventional cardiologist at Mass Gen's Heart Center and lead investigator with Kenneth Rosenfield, MD, says,

Heart: Prochymal Demonstrates Safety and Improvement in Heart Attack Victims

Osiris Therapeutics, reporting one year interim results of its Phase I trial on Prochymal for treatment of heart attack patients, announced that a "53 patient, double-blind, placebo-controlled trial has successfully shown Prochymal for the treatment of heart attack patients is safe and results in statistically significant improvement in heart function."  As a result, the Food and Drug Administration (FDA) has approved the initiation of a Phase II trial. "The data further suggest that the greater the cardiac damage, the greater the potential benefit from Prochymal," said Dr. Joshua Hare, M.D., lead investigator for the Prochymal cardiac study.

Stem Cell Digest Comment:  Prochymal, "a patented formulation of adult stem cells," is apparently a potential solution Osiris is planning for several diseases.  It is "currently in Phase III clinical trials for the treatment of Graft vs. Host Disease and Crohn's Disease.  It is also in a Phase II trial for type 1 diabetes."  Additionally, Osiris has received a "$224.7 million contract for the development and stockpile of Prochymal by the Defense Department for the treatment of acute radiation syndrome."

    Read the Osiris Therapeutics announcement.