At the International Regenerative Biomedical Technology Conference in Dubai, a U.S. physician presents the clinical results of adult stem cell therapy that was successfully used in the treatment of a number of patients with cardiovascular disease.

Zannos Grekos, M.D., chief medical officer of the Florida-based stem cell center Regenocyte Therapeutic, presented data before the Dubai Congress on Regenerative Biomedical Technologies which demonstrated the successful treatment of several end-stage cardiac diseases in a number of patients via autologous (in which the donor and recipient are the same person) adult stem cell therapy. The evidence that he presented included PET scans, nuclear scans and echocardiographs performed at 6 months and one year post-treatment, all of which confirm the regeneration of damaged heart tissue including newly stimulated angiogenesis and improved heart function in patients who were treated with their own adult stem cells that were extracted from their own blood.

As Dr. Grekos stated, “This is real science, real medicine and real results. We have moved beyond bench research and clinical trials to show that the power of the body’s adult stem cells can be harnessed. Our success rate in reversing ischemic cardiomyopathy and congestive heart failure is extremely high and with our latest technology we’re capturing the same astounding cell regeneration results in other disease classifications.”

Additionally, Dr. Grekos announced that his team of physicians and scientists also used autologous adult stem cells in the successful treatment of a patient with Fabry disease, which is caused by an enzyme deficiency that leads to heart and kidney failure and which previously has had no cure. Whereas an ejection fraction (EF) of 55 is considered normal for healthy patients, this particular patient with Fabry disease experienced an EF improvement from 28 to 41 in just four months after receiving the autologous adult stem cell therapy. According to Dr. Grekos, “The patient no longer needs a heart transplant, which was previously the only means for arresting this disease. His kidney dialysis time has already been reduced by 10%, so we are looking at treating his kidney function in the near future.”

Dr. Athina Kyritsis, chair of Regenocyte’s medical advisory committee, states, “As a physician I find one of the most exciting things this discovery offers is the potential to address many diseases currently believed to be untreatable. We are leaping off of medicine’s cutting edge. This is no longer just theory.”

The procedure involves the simple drawing of blood from which the adult stem cells are isolated and then expanded in the laboratory and administered to the patient a week later either through an injection or infusion delivery system. Because the stem cells are autologous (meaning that the donor and the recipient are the same person), there is no risk of immune rejection.

In addition to being the chief medical officer for Regenocyte Therapeutic, Dr. Zannos Grekos is associate clinical professor of cardiology for Nova Southeastern University and has been appointed to the Science Advisory Board of the Washington, D.C. based Repair Stem Cell Institute. In 2007, Dr. Zannos was invited to brief the United States Senate Health Advisory Staff on the current state of stem cell research and therapy. Regenocyte Therapeutic is currently using adult stem cell therapy to treat congestive heart failure, cardiomyopathy, peripheral artery disease, coronary artery disease, kidney disease, ischemic heart disease, pulmonary disease and early senile dementia. Clinical trials will begin in 2009 for patients with macular degeneration and various neurological diagnoses.

Mesenchymal stem cells (MSCs) are clinically attractive for a number of reasons which include, among other desirable qualities, their ease of intravenous administration, their ability to home-in on injured tissue, their proven ability to differentiate into a wide variety of tissue types, and their status as immune privileged “universal donor” cells, for which they are especially well known. Numerous clinical trials throughout the U.S. are currently in progress in which MSCs are intravenously administered to patients with a vast range of conditions, thereby validating MSCs as an already well-established and viable therapy. Especially in the treatment of myocardial infarction, allogeneic (in which the donor and recipient are different people) MSCs as a clinical therapy have yielded statistically significant benefits in cardiac patients.

Nevertheless, despite the already high level of success enjoyed by MSCs, scientists have been trying to improve the therapeutic efficacy of these highly potent adult stem cells even further. Now, through a process of molecular potentiation, a team of researchers has succeeded in attaining the goal.

Using MSCs which were modified to overexpress IGF-1, Dr. Husnain Haider and his colleagues at the University of Cincinnati in Ohio observed an overall improvement in cardiac regeneration which was associated with increased mobilization of endogenous bone marrow stem cells in an animal model of heart attack. The MSCs were transfected with this insulin-like growth factor gene, which previously has been found to play an important role in the efficacy of MSCs in a variety of therapeutic uses, including the reversal of kidney failure. Now Dr. Haider’s study indicates that the IGF-1-transfected MSCs also possess superior efficacy in inhibiting pathological changes in rats following myocardial infarction, through the CXCR4 (a CXC chemokine receptor) signaling mechanism in the paracrine release of SDF-1-alpha (stromal-derived-factor being a chemotactically active molecule for lymphocytes), which promoted improved survival and engraftment by the MSCs in the infarcted cardiac tissue. Among other roles, CXCR4, also known as fusin, is specific for SDF-1 (also known as CXCL12) and has been identified in the homing ability of hematopoietic stem cells, and is already recognized as an important receptor in a wide variety of molecular processes.

Dr. Haider’s results corroborate a recent study conducted by Dr. Kondo of Japan, in which angiogenesis from exogenously administered bone marrow stem cells in an animal model of critical limb ischemia was found to be highly dependent upon the moblization of endogenous bone marrow stem cells which were activated by the exogenous stem cells. Now Dr. Haider’s group has observed that the ability of the exogenously administered MSCs to repair cardiac tissue and to inhibit further post-infarct pathological changes following a heart attack is also dependent upon the mobilization of endogenous bone marrow stem cells.

The role of IGF-1 in mobilizing endogenous bone marrow stem cells through paracrine activation of SDF-1-alpha/CXCR4 signaling, thereby increasing and improving the therapeutic efficacy of MSCs, is a discovery which may also prove to have additional applications in the potentiation of other types of stem cells.

Known as The Marvel Study, clinical trials are currently underway on two continents for the largest study ever to be conducted in the treatment of congestive heart failure with adult stem cells. Directed by Dr. Alan Niederman of the Jim Moran Heart and Vascular Research Institute at Holy Cross Hospital in Miami, the study consists of 330 patients who are enrolled in the trials at 30 separate investigational sites throughout the U.S. and Europe. The study involves the exclusive use of autologous adult stem cells as therapy.

The stem cells are drawn from each patient’s own thigh muscle and injected directly into the heart. According to Dr. Niederman, “This is what’s known as the pivotal study. If this study is positive, they will go to the FDA to approve this technique as a broad technique that everybody can particupate in.”

Previous studies indicate that improvement is often seen in the patient within a few weeks after receiving the stem cell therapy.

Aldagen, Inc., a biopharmaceutical company specializing in the development of proprietary regenerative cell therapies, reports the commencement of Phase III clinical trials for their newest and most advanced adult stem cell product. Known as ALD-101, and believed to be able to accelerate neutrophil and platelet engraftment following cord blood transplantation, the product was developed from adult stem cells that were isolated from umbilical cord blood. 40 pediatric patients with inherited metabolic diseases who have been selected for the study will receive a cord blood transplant in combination with ALD-101. In previous Phase I and II clinical trials, 24 patients who received ALD-101 showed a statistically significant reduction in platelet engraftment time when compared to controls who had not received ALD-101.

A number of inherited metabolic diseases have already been shown to be treatable with adult stem cells derived from cord blood, including Adrenoleukodystrophy, Metachromatic Leukodystrophy, Krabbe’s Syndrome and Hurler Syndrome, all of which have few treatment options and are often fatal. Now, products such as these developed by Aldagen offer yet a further improvement in the efficacy of such therapies.

In addition to ALD-101, Aldagen also has several other adult stem cell products which include ALD-151, which is designed to improve cord blood transplants in the treatment of leukemias, ALD-301 which was developed for the treatment of critical limb ischemia, and ALD-201 which was developed for the treatment of ischemic heart failure.

Mesenchymal stem cells (MSCs) are of great therapeutic interest because they are already known to be not only regenerative but also immune privileged and immune modulatory, unlike most stem cells. Such characteristics eliminate any need for matching MSCs immunologically to the recipient, and because of these "immune privileged" properties, the biotech company Osiris Therapeutics holds a number of patents on MSCs for a variety of allogeneic uses of MSCs such as the intravenous delivery of these stem cells in the treatment of patients with heart failure. Now the extraordinary properties of MSCs have been applied to yet another medical application, namely, to expediting the process of wound healing.

Dr. Yoshikawa and colleagues at the Nara Medical University in Japan have successfully mimicked an artificial dermis layer by culturing bone marrow-derived MSCs on a collagen sponge from which the layer of dermal cells was then implanted subcutaneously into an immune-compromised mouse and explanted after ten days, at which time histological examination revealed the differentiation of the MSCs into dermal tissue in vivo.

The procedure was then applied to 20 human patients who were suffering from pathological skin conditions that were refractory to conventional medical therapies, and for whom the same type of autologous "grafts" were applied to the wound areas after having been created from each patient’s own bone marrow-derived MSCs and the collagen matrix. From this procedure, 18 of the 20 patients were found to have significantly improved.

The procedure offers a promising new therapy for even some of the most severe types of wounds.

The administration of adult bone marrow stem cells (BMC) and mesenchymal stems cells (MSC) can aid in the recovery of myocardial infarction (MI) – commonly known as heart attack – and consequently increase survival rates according to a study in the Clinical and Experimental Pharmacology and Physiology published by Wiley-Blackwell.

The study is designed to evaluate the impact of systemic delivery of BMC and MSC on spontaneously hypertensive rats induced with MI.

Dr. Nardi, the lead author of the study called,

An unprecedented feat that could signal the beginning of the end of organ shortages has been achieved by doctors who have stripped down and refurbished a dead heart so that it can beat again.

According to the American team, the shortage of replacement hearts and other organs could be overcome with the new research. The need for anti-rejection drugs could also be completely avoided.

The research, conducted by researchers at the University of Minnesota, could pave the way to a new treatment for the 22 million people worldwide who live with heart failure. The journal Nature Medicine described the the world’s first beating, retooled “bioartificial heart”.

To begin, cells were removed from a whole heart. The blood vessel structure, valves, chambers, and full architecture of the heart were left intact, and repopulated with new cells.

“We just took nature’s own building blocks to build a new organ,” says Dr. Harald Ott, a co-investigator who now works at Massachusetts General Hospital. “When we saw the first contractions we were speechless.”

The work has huge implications: “The idea would be to develop transplantable blood vessels or whole organs that are made from your own cells,” said Professor Doris Taylor, director of the Center for Cardiovascular Repair, Minnesota, principal investigator.

Virtually any organ with a blood supply could be created with the new method. The list includes the pancreas, lungs, kidneys, and liver.

Although costs make it prohibitive at present, Taylor is ready to grow a human heart. But she admits that the method is “years away” from being used in hospitals.

“We could begin with human cells and pig or human scaffold now but creating the larger bioreactors (the vessels in which the organs are grown) and generating the reagents and growing enough cells would cost tens of thousands of dollars for each heart at this point.”

“That is just too expensive to answer basic questions. We of course want to move in that direction, but funding is limited. As we can we will go forward – perhaps one heart at a time.”

Individuals face life long immunosuppression after an organ transplant. And over the long term, kidney failure, diabetes, and high blood pressure are the trade off for heart failure when using drugs to prevent rejection. Even getting to the point of performing the transplantation operation is difficult since donor organs are limited.

Researchers believe a new heart created by decellularization is much less likely to be rejected by the body since the heart is filled with the recipient’s own stem cells.

And once placed in the recipient, in theory the heart would be nourished, regulated, and regenerated similar to the heart that it replaced.

“We used immature heart cells in this version, as a proof of concept. We pretty much figured heart cells in a heart matrix had to work,” Professor Taylor says. “Going forward, our goal is to use a patient’s stem cells to build a new heart.”

As for the source of the cells from a heart patient, she says: “From muscle, bone marrow, or heart; depending on where the science leads us.”

Professor Taylor says that decellularization shows potential to change how scientists think about engineering any organ, even though heart repair was the initial goal.

“It opens a door to this notion that you can make any organ: kidney, liver, lung, pancreas – you name it and we hope we can make it,” she added.

According to UK Transplant, 81 people are waiting for heart transplant. Even though 28 patients died while waiting for a transplant last year, 155 patients had their lives saved or transformed by a heart transplant.

Typically, only 3,000 transplants are performed every year, despite more than 9,000 patients making up the waiting list nationally. While waiting, 1,000 people died last year.

A UK Transplant spokesman says: “These developments offer long term hope and long may they continue but the real problem now is a desperate shortage of donated hearts.”

Dr. Tim Chico, Consultant Cardiologist, University of Sheffield, says: “This is an ingenious step towards solving a massive problem. Heart failure (an inability of the heart to pump sufficient blood, usually after a heart attack) is increasing in the UK.”

“A chronic shortage of donors for heart transplantation makes stem cell therapy appealing. The study is very preliminary, but it does show that stem cells can regrow in the ‘skeleton’ of a donor heart. However, it will take a lot of further work to assess whether this will ever be a viable option for patients.”

Professor Wayne Morrison, Director of the Bernard O’Brien Institute of Microsurgery, Melbourne, comments: “This is the first time a whole organ has been tissue engineered outside the body.”

“They have demonstrated that they can create a heart that looks like a heart and is shaped like a heart and, most excitingly, that they can re-establish the blood vessels that were originally there. It is this ‘regrowth’ of the blood vessel cells that gives the potential in the future to connect this structure to a blood vessel in the body and then get circulation to go through it.”

“This very exciting study,” comments Dr. Jon Frampton, University of Birmingham. “Although this is only a first step requiring considerable follow-up development, the study nevertheless represents an exciting breakthrough that will eventually make the prospect of repairing damaged hearts a reality and will also be an approach that can be extended to other organs.”

Dr. Anita Thomas at the Australian Institute for Bioengineering and Nanotechnology, University of Queensland, adds: “There is one more major step to achieve before we can proceed any further: we need to see what happens when these artificial hearts are placed in a recipient animal for any length of time. The authors of the article have the necessary skills and yet have not reported their results. We wait with anticipation for their next publication.”

There have been advances in growing heart tissue in the laboratory but the complex architecture and intricacies of the body’s primary pump have to be mimicked exactly in order to be fully successful. Until now, the problem has been how to create a 3D scaffold that could do this.

This is why “decellulariazation” became the method of choice for Professor Doris Taylor and her colleagues. The process leaves only the extracellular matrix, the framework between the cells, intact, along with the plumbing and heart valves. This is accomplished by using a detergent to remove all the cells from the organ – in this case, an animal cadaver heart.

Taking immature cells that came from newborn rat hearts, researchers injected rat hearts with this mixture and placed the structure in a sterile chamber in the lab to grow. This was done after first removing the cells from both rat and pig hearts using a detergent.

Professor Taylor said the results were very promising. Contractions were observed in the hearts four days after seeding the decellularized heart scaffolds with cells. Even though it was only at two percent of the efficiency of an adult heart, the hearts were pumping eight days later.

A study at of the hearts at the cellular level revealed that the “cells have many of the markers we associate with the heart and seem to know how to behave like heart tissue.”

For many patients who have run out of options, a new treatment could offer new hope.

The treatment is for patients who have had stents, surgeries, and other treatments without success. These patients suffer from severe coronary artery disease and are at great risk for heart attacks and progressive heart failure.

An injection of stem cells being tested by doctors at Chicago’s Rush University Medical Center with the hope that it will alleviate the problems patients have with their hearts.

Medical history may be made by James Campbell. The sixty-eight year old heart patient has volunteered to have an injection administered directly into his heart. The injection will be blind, meaning that he could possibly be injected with a placebo. But hopefully, the injection will be a special type of stem cell. Campbell is participating in a clinical trial to see if new blood vessels can be grown with stem cells.

“If it works, it’s worth it,” Campbell said.

“The hope is that these endothelial progenitor cells will grow and divide and allow and facilitate new blood vessels to enter that region of the heart muscle that’s not getting enough blood and oxygen,” said Dr. Gary Schaer, director of cardiac catherization at Rush.

Campbell wants to end the debilitating and chronic chest pain he has suffered for three years. He has survived through a heart attack and two heart surgeries already.

“I can walk maybe 60 to 65 feet and I start having chest pains,” Campbell said.

The day before the injection, Campbell donated his own stem cells like every other patient also enrolled in the trial.

“The advantage of the patient’s own stem cells is there’s no chance of rejection,” Schaer said.

Dr. Schaer says the no ethical issues come into play for this treatment. Several dozen patients like Campbell have been injected by Dr. Schaer using 3-D computer mapping and sophisticated catheter technology since the trial started. The results have been incredibly encouraging and there have been no adverse reactions.

“The patients that we’re seeing in follow up, and we’ve seen several that have come back for their one year follow up, we’ve seen marked improvements in their symptoms,” Schaer said.

The current trial is still recruiting patients. But Rush Medical has more trials planned, with different diseases and different kinds of stem cells.

Some of Campbell’s hobbies prior to his heart problems were riding motorcycles and canoing. He is hoping that the injections will alleviate his pain, and allow him to go back to a normal life where he can be active again.

The FDA approved clinical trials for adult stem cells to the tune of 1100 in 2006. But 2007 was even more successful for adult stem cells. Over 1400 FDA approved trials for 73 different conditions in humans where patient health has been improved through adult stem cell therapy were documented in peer-reviewed studies in 2007.

Umbilical cord blood, placentas, and other tissues in the body contain adult stem cells. They are found throughout the entire body. No embryos are destroyed when extracting adult stem cells, which is in contrast with the extraction of embryonic stem cells.

We have decided to publish a yearly update each fall/winter since treatments with adult stem cells are continually increasing and continue to be impressive. (Note: Embryonic stem cells have never produced successful treatment trials in humans.)

Adult stem cells do not create tumors, unlike embryonic stem cells.

The research and treatments involving adult stem cells has been fast paced since our 2006 paper, thus, we have summarized some of the developments in the field below.

The Regeneration of Heart Tissue

Eight years ago, Doug Rice was diagnosed with congestive heart failure. Due to his diabetes, he was unable to get a heart transplant.

Rice decided to travel offshore for adult stem cell treatment since he was facing fatal heart failure. Stem cells were extracted from a sample of blood taken from Rice. The cells were differentiated into angiogenic cell precursors, then transplanted into Rice’s heart.

The results were immediate for Rice, who experienced an increase in his hearts efficiency of 30 percent. He originally had an ejection fraction of 11 percent.

According to Rice, “I’ve been around a lot of people with bad hearts. I know if they looked at [adult stem cell therapy], it might save their lives. I firmly believe it saved mine.”

A few other companies have developed adult stem cell technology for heart patients.

Marc Penn, director of the Bakken Heart Brain Institute at the Cleveland Clinic, says of one new therapy, “It’s very exciting, perhaps a sea-changing trial for the field … offering the chance of an off-the-shelf-product.”

Bone marrow stem cells have been used by Bodo-Eckehard Strauer to treat over 300 heart patients. He is the director of the cardiology department at Dusseldorf University Hospital. A patient who was

Using autologous stem cells, 28 patients were recently treated for acute myocardial infarction (MI) at the Sir Hurkisondas Nurrotumdas (HN) Hospital in Mumbai, India. The Medical Research Society of HN Hospitals funded the research. Patients from the 39-68 years age group were chosen for the project which was started in June of 2005.

“Most attempts including ours have considered the adult bone marrow as the source of the repair stem cells which is a source of hematopoietic and stromal stem/progenitor cells and have demonstrated that the implantation procedure is safe, feasible and effective in terms of improving the myocardial salvage rate of the infarcted myocardium. The latter can be attributed to the angiogenic events or secretion of angiogenic cytokines by these cells,” said Dr. VK Shah, Principal Investigator and Interventional Cardiologist, HN Hospital.

Facilitating the ability of the heart to heal itself, patient’s own bone marrow stem cells reach the infarcted area with the blood supply and contribute to the restoration of stem cell niches. The patient’s cells are injected into the culprit coronary artery after the opening of the occlusion by primary angioplasty.

“All the cases were successful without any complications. This procedure is done while the patient is fully conscious,” Dr. Shah claimed.

Further explaining the process, Dr. Shah said, “We have completed clinical check-up of all the patients of two, four, six and twelve weeks. Further a six-month follow-up of left ventricular (LV) function assessment by LV angiography and cardiac magnetic resonance imaging in stem cell therapy group have demonstrated an increase in LV ejection fraction (EF) by 7-12 per cent as compared to 1-3.2 per cent controls. There is improvement in LV systolic function, wherein LV end systolic volume (LVESV) has decreased significantly to 16-28 per cent. No patient has demonstrated deterioration of regional wall motion or any other side effects during the follow-up period. The results of our study show favourable trend towards improvements of cardiac functions which is the key determinant for long-term survival.”

In order to see what the long term effects of bone marrow infusion on any organ are, the hospital has carried out some routine tests at the end of two years. Normal in all patients were; lipid profile, renal function tests, liver function test, chest X-ray, sonography of abdomen and blood tests which include complete haemogram, ECG, and 2D echocardiography. The detailed clinical evaluation was performed on all patients starting with the first who received bone marrow stem cell therapy.

“In addition to the regular clinical follow-up, these tests helped us in assessing the safety and feasibility of transfusing autologous bone marrow stem cells (ABMSC) into the culprit coronary artery after an acute anterior wall MI,” said Dr. Shah.

According to patient Rajaram Chandra Jagdale (54), who underwent the therapy last April after suffering from an acute MI, “I am doing fine after the therapy.”