Adult Stem Cells Act as Pacemaker

Scientists at the Chiba University Graduate School of Medicine in Japan have announced their discovery of a natural "biological pacemaker" in adult stem cells derived from adipose (fat) tissue. Specifically, the adult stem cells are mesenchymal stem cells (MSCs), and their naturally occurring "pacemaker" qualities may someday be useful in correcting electrical problems in the heart.

According to Dr. Toshinao Takahashi of the Chiba University, "Electronic pacemakers are often used as palliative therapy for people who have conduction problems with the electrical signals that govern the heart beat. However, that therapy has several shortcomings, including possible malfunction and the need for repeated replacement of the device’s power packs and electrodes. Cell therapy could overcome those problems and provide a possible cure for conductive disease. Our goal is to create a biological pacemaker."

The researchers harvested MSCs from the adipose tissue of mice which were then differentiated into beating cells which resembled heart cells in all features including cell surface proteins that serve as cardiac chemical markers. The new cells were then injected into mice who suffered from atrioventricular (AV) block, an electrical signaling problem of the heart which results in an abnormally reduced heart rate. Within a week after treatment with the new cells, the AV block was reversed to some extent, either completely or partially, in half of the mice who received the stem cell transplant.

Adipose tissue is known to be a rich source of MSCs which have been shown in numerous studies to differentiate into a wide variety of tissue types such as bone, muscle, liver, neuron and cardiac cells, among others. As the name implies, MSCs possess qualities of the "mesenchyme" – the unspecialized matrix cells that are found in the early embryo – which is in fact derived from all 3 germ layers, so one would therefore logically expect MSCs to be able to differentiate into most if not all cell and tissue types of the adult human body. Additionally, adipose tissue is known to exhibit a number of unique immunomodulatory properties which would also prove to be especially beneficial in the treatment of a variety of diseases and injuries (as recently reported by N.H. Riordan et al. in a publication in the April 24, 2009 issue of the Journal of Translational Medicine entitled, "Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis").

In the particular treatment of disorders stemming from problems in cardiac electrical conduction and signaling, Dr. Takahashi has concluded that, "Our findings suggest that brown-fat-derived mesenchymal stem cells may become a useful cell source for antiarrhythmic therapy."

The results were presented at the American Heart Association’s Basic Cardiovascular Sciences Conference in Dallas.

Leading Researcher Joins Cellular Dynamics

Junying Yu, Ph.D., formerly an associate scientist and senior research fellow in Dr. James Thomson’s laboratory at the University of Wisconsin at Madison, has accepted an invitation to join the scientific research staff of Cellular Dynamics International (CDI), the company cofounded by Dr. Thomson.

According to Chris Kendrick-Parker, chief commercial officer at CDI, "Dr. Yu strengthens CDI’s scientific team and our ability to exploit our growing patent portfolio. Junying is one of the top stem cell researchers in the world, and with her on our team we feel confident that we will be able to provide additional, much needed stem cell research tools and therapies to the preclinical, and eventually clinical, market faster."

As Robert Palay, chairman and CEO of CDI, adds, "We are very pleased that, of the many offers Dr. Yu has entertained, she has chosen CDI to further her research and career. Her personal goals align with the company’s goals in being the leader in iPS cell technology, industrializing the process to create the quantity of cells required for use as tools and therapeutics and accelerating the process of bringing personalized medicine to realization."

As Dr. Yu stated, "I’m excited to join the team of scientists at CDI working towards personalized therapeutics. In vitro drug testing can be severely limited by the lack of physiologically relevant models arising from non-human animal models or models that do not appropriately reflect the target population. iPS cell technology overcomes these obstacles and offers the promise of generating differentiated cell types from virtually any genetic background."

Though already distinguished for her collaboration on a number of pioneering breakthroughs, in March of this year Dr. Yu received further recognition for her participation in the development of iPS cells without the use of dangerous viral vectors, a significant achievement which was described in an article published in the journal Science. This new procedure for developing iPS cells – which CDI has termed "iPS 2.0" – brings iPS cell technology one step closer to clinical applications. Prior to this particular breakthrough, Dr. Yu had already garnered attention for her participation in previous stem cell milestones which included the historic announcement in a November 2007 publication in Science in which she and the other members of Dr. James Thomson’s team first described the successful creation of iPS cells from human skin.

According to Dr. Thomson, one of the cofounders and currently the chief scientific officr of CDI, "It has been an absolute privilege to work with Junying for the past six years at UW, and I am excited to continue the relationship. Junying could have gone anywhere, but she chose CDI, an endorsement of which I am proud. I have always been optimistic in CDI’s success, however now I have great confidence. If Junying takes on a project, it succeeds."

Dr. Yu’s appointment to CDI follows a series of other recent announcements by the company that have included two exclusive licensing agreements – one with New York’s Mount Sinai School of Medicine, and the other with IUPUI, the Indiana University-Purdue University Indianapolis – as well as a new scientific breakthrough in which the company announced the first successful creation of iPS cells from normal human blood.

Based in Madison, Wisconsin and co-founded by the renowned embryonic stem cell pioneer Dr. James Thomson along with 3 of his colleagues in 2004, CDI specializes in the development of iPS cells for drug screening. Often referred to as "the father of embryonic stem cell science", James Thomson, VMD, Ph.D., was the first person ever to isolate an embryonic stem cell in the laboratory, first from a nonhuman primate in 1995 and then from a human in 1998. In addition to serving on the Board of Directors and as chief scientific officer of CDI, Dr. Thomson is currently also director of Regenerative Biology at the Morgridge Institute for Research and the John D. MacArthur Professor of Anatomy at the University of Wisconsin at Madison.

As anyone can see, clearly printed at the top of CDI’s website is the phrase, "iPS cells deliver". Contrary to popular opinion, therefore, and despite his distinguished background in embryonic stem cell (ESC) research, Dr. Thomson is no longer focused exclusively on ESCs but instead has turned the focus of his attention to iPS cells, of which he is also a co-discoverer and which he often describes as having a more immediate applicability in medicine than ESCs. Additionally, such an applicability of iPS cells is not so much in the development of actual cell-based therapies as it is in the screening of new pharmaceuticals, as clearly indicated by the commercial direction of CDI’s pipeline. As further described on their website, "Cellular Dynamics is working with scientists worldwide to develop and deploy a number of cell lineages derived from human pluripotent stem cells (hPSCs) as well as a wide range of screening assays and services to aid pharmaceutical development. Currently CDI provides cardiac toxicity drug testing services, including GLP and non-GLP hERG channel electrophysiological assays as well as action potential and cytotoxicity screens using cardiomyocytes. The company is developing additional cell types from iPS cells, including hematopoietic cells (mast and CD34+ cells, megakaryocytes, and red blood cells), hepatocytes, neural cells, adipocytes, and more."

(Please see the related news articles on this website, entitled, "Wisconsin Stem Cell Company Announces Licensing Agreement", dated July 15, 2009; "Cellular Dynamics Creates iPS Cells From Human Blood", dated July 8, 2009; and "Cellular Dynamics and Mount Sinai Sign Licensing Agreement", dated May 29, 2009).

NeoStem Featured on CBS

The first company to commercialize a method by which healthy adults may bank their own stem cells, NeoStem was the subject this past Sunday of the CBS television feature, "Eye on New York City".

NeoStem has pioneered a process by which endogenous adult stem cells that naturally reside in the bone marrow are "mobilized" to migrate into the peripheral blood, from which they are then collected through a process known as apheresis. Routinely used in other procedures such as the donation of blood platelets, apheresis allows stem cells to be easily separated from the other cells in the blood, so that the non-stem-cell cells may then be returned to the individual after the stem cells are removed. Apheresis is a minimally invasive, painless process that typically lasts approximately 3 to 4 hours, during which time the patient is awake and comfortable – all of which is highly preferable to bone marrow aspiration, the procedure for harvesting adult stem cells from bone marrow but which must be performed under general anesthesia due to the high level of pain that it causes. After the adult stem cells are collected via apheresis, the stem cells are then stored via a cryopreservation method and remain available to the individual indefinitely throughout the future for therapeutic use whenever needed.

According to Dr. Max Gomez, medical expert for CBS, autologous adult stem cells "have become the cutting edge way to treat osteoarthritis of the knee, hip, ankle and even back pain", among other ailments. Additionally, he adds, "The promise appears to be so great that more than 1,000 clinical trials are testing (autologous adult) stem cell therapies for various conditions and showing promising results for heart failure, diabetes, lupus and even macular degeneration", among other conditions.

According to Dr. Robin Smith, CEO of NeoStem, "NeoStem is very focused on autologous adult stem cell therapies being developed for multiple diseases." Among NeoStem’s recent acquisitions is an exclusive license for use of the technology which identifies and isolates VSELs (very small embryonic-like stem cells), which are not actually embryonic stem cells but nevertheless resemble embryonic stem cells in their pluripotency, and which are believed to have a number of potential clinical applications to the treatment of various diseases.

According to the company’s website, "NeoStem is the first company to provide adult stem cell collection and banking services to the general adult population. NeoStem’s medically proven process is a minimally invasive, painless and safe way to collect your adult stem cells. … There are tremendous clinical and economic advantages to autologous stem cell transplantation (receiving your own stem cells) as there are no issues with immune rejection. Engraftment with your own stem cells is faster, safer and much less costly than receiving someone else’s stem cells (allogeneic)." Additionally, as NeoStem points out on their website, "Currently, adult stem cell transplants have been successfully used as the standard of care in treating blood cancers such as leukemia, lymphomas and multiple myelomas. Today, over 2,000 clinical trials are being conducted in the United States looking at treatments for other diseases such as heart disease, diabetes, vascular disease, autoimmune disorders such as lupus, multiple sclerosis, Crohn’s disease, and many more. In addition, adult stem cells are now being used for certain cosmetic procedures and evaluated for further ones."

According to the actress Suzanne Somers, who has utilized NeoStem’s services for banking her own adult stem cells, "Stem cell therapy is the most exciting new breakthrough in medicine. It gives me great peace of mind to know that my own stem cells will be banked as bio-insurance for me. Now I am prepared for my future as the beneficiary of medical benefits while I am alive."

In June of this year, NeoStem signed an exclusive 10-year-long contract with the China-based company Enhance Biomedical Holdings for a collaboration in the development of a network of adult stem cell collection and treatment centers in Taiwan and throughout a number of provinces in China. (Please see the related news articles on this website, entitled "NeoStem Signs Adult Stem Cell Agreemenet in China", dated June 15, 2009, and "NeoStem CEO Invited to Address Medical Tourism at Conference", dated September 8, 2008).

Adult Stem Cells Treat Alzheimer’s in Animals

Researchers at the Burnett School of Biomedical Sciences at the University of Central Florida today announced positive results in the treatment of Alzheimer’s disease with adult stem cells in mice.

Led by Dr. Kiminobu Sugaya, the scientists used a unique combination of neural stem cells differentiated from bone marrow-derived mesenchymal stem cells, together with the compound phenserine – a highly selective AChE (acetylcholinesterase) inhibitor – to treat a mouse model of Alzheimer’s disease. Not only did the scientists observe the regeneration of new neurons in the brains of the mice following the treatment, but they also found a significant reduction in the amyloid plaque that characterizes Alzheimer’s disease.

According to Dr. Sugaya, "If our success with mice can translate into the human brain, it could give hope to patients and their families."

Alzheimer’s disease is characterized by very specific neurological abnormalities which ultimately result in very specific types of behavioral abnormalities. Neurologically, there are 3 main identifying features of Alzheimer’s disease, namely, 1) beta-amyloid plaques, which form outside and around neurons, 2) neurofibrillary tangles, which form inside dead neurons, and 3) overall dramatic shrinkage of neural tissue. The plaques and tangles in particular have come to be regarded as the hallmarks of Alzheimer’s, although it is not yet known whether these features are a cause of the disease or merely a byproduct. The gross atrophy of the brain that is seen in advanced stages of Alzheimer’s is a result of the widespread death of neuronal cells, and the concomitant loss of their synaptic connections. In severe cases the brain may be reduced by as much as a third of its normal size. Behaviorally, the symptoms of Alzheimer’s disease are often mistaken in the early stages for a normal part of the aging process. However, Alzheimer’s does not represent normal aging.

The website of the National Institute of Neurological Disorders and Stroke (NINDS), a branch of the National Institutes of Health (NIH), offers the following official definition: "Alzheimer’s disease is a progressive, neurodegenerative disease characterized in the brain by abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary tangles) composed of misplaced proteins." Also on the same website, the NINDS researchers further add that, "There is no cure for Alzheimer’s disease and no way to slow the progression of the disease."

Indeed, prior to the advent of stem cell technology, conventional medicine offered no known effective therapy for Alzheimer’s. Now, however, adult stem cell therapy may possibly offer the first type of treatment which not only slows the progression of the disease by eliminating the plaques and tangles, but which also reverses symptoms of the disease by regenerating new neurons.

Dr. Sugaya has previously published a number of studies characterizing the physiological function of the beta-amyloid precursor protein, as well as the ability of bone marrow-derived mesenchymal stem cells to differentiate into both neurons and glia. As stated on his webpage, Dr. Sugaya is focused on the ultimate development of a neuroreplacement therapy using human mesenchymal stem cells for the treatment of a number of neurodegenerative diseases which include Alzheimer’s.

Approximately 37 million people worldwide suffer from various forms of dementia, with Alzheimer’s disease constituting the majority of cases. It has been estimated that 18 million people throughout the world are afflicted with Alzheimer’s, approximately 5.3 million of whom are in the U.S., and these figures are expected to double by the year 2025. Although Alzheimer’s is often associated with industrialized societies, currently over half of all people who suffer with this disease are reportedly living in developing nations.

In addition to U.S. President Ronald Reagan, many other prominent individuals have suffered from Alzheimer’s disease, including the former Prime Minister of Britain, Harold Wilson, the choreographer George Balanchine, the composer Aaron Copeland, and the actress Rita Hayworth.

(Please see the related sub-section on this website, entitled "Alzheimer’s Disease", listed in the "Research" section).

Enrollment Begins in Adult Stem Cell Clinical Trial for Ischemic Stroke

The Canadian company Stem Cell Therapeutics (SCT) has received authorization from the Drug Controller General of India (DCGI) to begin enrollment in the Phase IIb clinical trial for the treatment of acute ischemic stroke with adult stem cells.

The double-blind, randomized, placebo-controlled clinical trial, which has a recruitment target of 128 to 130 patients, will utilize the modified REGENESIS proprietary protocol developed by SCT. Dr. Steven C. Cramer from UC-Irvine and Dr. Michael D. Hill of the University of Calgary are the two principle investigators of the study.

According to Dr. Alan Moore, president and CEO of SCT, "Approval from DCGI to initiate recruitment for the modified REGENESIS stroke trial in India is an exciting milestone for SCT. Jurisdictional approvals have now been granted in India, the U.S. and Canada, therefore we will begin recruiting patients as soon as possible."

In accordance with their regulations, the DCGI states that, "The DCGI approval process categorizes clinical trials into two types. If the study protocol has already been approved by a cognizant regulatory authority in one or more developed countries (such as the U.S., Canada, the U.K., Switzerland, Germany, Australia, Japan, and South Africa), the study is classified as a Type A trial and can be approved using a fast-track process within two to six weeks after the required documentation has been submitted. All other studies are classified as Type B. For these, the approval process is generally 8 to 12 weeks. The Institutional Review Board (IRB) approval process can be conducted in parallel with the DCGI review and, if import licenses are needed, the applications for these can also proceed in parallel. These provisions facilitate the process of getting study protocols in place and quickly initiating the trials." In other words, India is an excellent place in which to conduct clinical trials, since the approval process moves much more quickly than it does in many other countries. A number of businesses from the U.S., the U.K. and Europe are therefore turning to countries such as India for the testing and commercialization of their new medical products, whether related to stem cells or not.

In this particular case, the therapeutic product developed by SCT, known as REGENESIS, contains a proprietary combination of compounds which are designed to stimulate the body’s naturally occurring, endogenous adult stem cells for the healing and repair of damaged tissue. As described on the company’s website, "Stem Cell Therapeutics Corp. is a Canadian public biotechnology company focused on the development and commercialization of drug-based therapies to treat central nervous system diseases. SCT is a leader in the development of therapies that utilize drugs to stimulate a patient’s own resident stem cells. The Company’s programs aim to repair brain and nerve function lost due to disease or injury. The Company’s extensive patent portfolio of owned and licensed intellectual property supports the potential expansion into future clinical programs in numerous neurological diseases such as traumatic brain injury, multiple sclerosis, Huntington’s disease, Alzheimer’s disease, and ALS."

Adult Stem Cells Restore Memory in Mice

Scientists at the Institute for Memory Impairments and Neurological Disorders at UC-Irvine have used neural stem cells derived from normal, healthy mice to treat other mice that had been genetically engineered to form the neurofibrillary plaques and tangles that characterize Alzheimer’s disease. Just a month after receiving transplantation with the neural stem cells, the diseased mice were found to perform significantly better on memory tests. Further analysis revealed that the neural stem cells alone did not diminish the plaques and tangles in the brains of the mice, nor did the stem cells increase the number of neurons, but instead the stem cells were able to improve cognitive function by strengthening and increasing the number of connections between already existing neurons. The results of this study therefore offer very concrete evidence for the importance of "neural networks" – the brain’s biological circuitry – in cognitive health. A hot topic in the 1990s, neural networks have proven to have a number of applications not only in neuroscience but also in computer engineering fields that include artificial intelligence. Among other things, the large-scale mathematical modelling of synaptic connections and their signaling resulted in the development of highly specialized "learning paradigms" and numerous types of neural network software which continue to have a broad range of applications to machine vision, mapping, virtual reality and any type of adaptive process. Now, a number of studies such as this, which are using stem cells to investigate the various mechanisms of the brain, are shedding further insights into a fundamental neurobiological process which translates readily to a wide variety of modern technological applications.

In the UC-Irvine study, the researchers found that most of the stem cells that were transplanted into the brains of the mice differentiated into astrocytes and oligodendrocytes, as only approximately 6% of the transplanted stem cells actually differentiated into neurons. Most importantly, the transplanted stem cells were found to secrete the protein BDNF (brain-derived neurotrophic factor) which stimulated the growth of neurites – a newly sprouted neuron that can grow into either an axon or a dendrite – thereby strengthening and increasing the number of connections between neurons. Conversely, when the scientists selectively reduced BDNF in the stem cells, the strength and number of the neuronal connections was observed to decrease, as did memory in the mice, thereby offering further evidence for the role of BDNF in maintaining healthy neuronal function and memory. When the scientists injected only the BDNF, without the stem cells, directly into the brains of diseased mice, some cognitive improvement was seen though not as much as when the BDNF was secreted directly by newly transplanted neural stem cells.

According to Dr. Mathew Blurton-Jones of UC-Irvine, the lead author of the study, "If you look at Alzheimer’s, it’s not the plaques and tangles that correlate best with dementia, it’s the loss of synapses – the connections between neurons. The neural stem cells were helping the brain form new synapses and nursing the injured neurons back to health."

As Dr. Frank LaFerla, a coauthor of the study, adds, "Essentially, the cells were producing fertilizer for the brain. This gives us a lot of hope that stem cells or a product from them, such as BDNF, will be a useful treatment for Alzheimer’s."

Alzheimer’s disease is characterized by very specific neurological abnormalities which ultimately result in very specific types of behavioral abnormalities. Neurologically, there are 3 main identifying features of Alzheimer’s disease, namely, 1) beta-amyloid plaques, which form outside and around neurons, 2) neurofibrillary tangles, which form inside dead neurons, and 3) overall dramatic shrinkage of neural tissue. The plaques and tangles in particular have come to be regarded as the hallmarks of Alzheimer’s, although it is not yet known whether these features are a cause of the disease or merely a byproduct of the disease. The gross atrophy of the brain that is seen in advanced stages of Alzheimer’s is a result of the widespread death of neuronal cells, and the concomitant loss of their synaptic connections. In severe cases the brain may be reduced by as much as a third of its normal size. Behaviorally, the symptoms of Alzheimer’s disease are often mistaken in the early stages for a normal part of the aging process. However, Alzheimer’s does not represent normal aging.

The website of the National Institute of Neurological Disorders and Stroke (NINDS), a branch of the National Institutes of Health (NIH), offers the following
definition: "Alzheimer’s disease is a progressive, neurodegenerative disease characterized in the brain by abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary tangles) composed of misplaced proteins." Also on the same website, the NINDS researchers further add that, "There is no cure for Alzheimer’s disease and no way to slow the progression of the disease."

Indeed, prior to the advent of stem cell technology, conventional medicine offered no known effective therapy for Alzheimer’s. Now, however, adult stem cell therapy may possibly offer the first type of treatment which not only slows the progression of the disease by eliminating the plaques and tangles, but which also reverses symptoms of the disease by regenerating new neurons.

Approximately 37 million people worldwide suffer from various forms of dementia, with Alzheimer’s disease constituting the majority of cases. It has been estimated that 18 million people throughout the world are afflicted with Alzheimer’s, approximately 5.3 million of whom are in the U.S., and these figures are expected to double by the year 2025. Although Alzheimer’s is often associated with industrialized societies, currently over half of all people who suffer with this disease are reportedly living in developing nations.

In addition to U.S. President Ronald Reagan, many other prominent individuals have suffered from Alzheimer’s disease, including the former Prime Minister of Britain, Harold Wilson, the choreographer George Balanchine, the composer Aaron Copeland, and the actress Rita Hayworth.

(Please see the related sub-section on this website, entitled "Alzheimer’s Disease", listed in the "Research" section).

Heart Damage in Mice Repaired With iPS Cells

Researchers at the Mayo Clinic in Rochester, Minnesota, have used induced pluripotent stem (iPS) cells to treat damaged cardiac tissue in a mouse model of heart attack. The iPS cells were found to repair the heart tissue both structurally and functionally.

According to Timothy Nelson, M.D., Ph.D., one of the lead investigators of the research, "This study establishes the real potential for using iPS cells in cardiac treatment. Bioengineered fibroblasts acquired the capacity to repair and regenerate infarcted hearts."

Previously, iPS cells had been tested in animal models for three other diseases, namely, Parkinson’s disease, sickle cell anemia, and hemophilia A. This new study is the first of its kind in which iPS cells were tested specifically for their ability to regenerate cardiac tissue.

As Dr. Nelson further explains, "We’re taking advantage of a diseased tissue environment that is sending out a distress signal that is asking the tissue to repair itself. When we put these iPS cells in, they are able to respond. They were able to respond to this damaged environment and spontaneously give rise to the appropriate tissues and create new tissues within that diseased heart. That is a key ‘wow factor’ of this paper. It was obvious to the observer which animals had been treated and which ones hadn’t."

The scientists used fibroblasts which they genetically reprogrammed to dedifferentiate into iPS cells which were then redifferentiated into heart tissue. When transplanted directly into the damaged hearts of the mice, the new cells were found to have engrafted within two weeks of transplantation, and by 4 weeks the transplanted cells were found to have contributed to improved structure and function of the hearts. Not only did the iPS cells halt the progression of structural damage within the heart muscle itself, but the iPS cells were also found to regenerate new cardiac tissue which included not only heart muscle but also blood vessels. Ultrasound also revealed significant improvement in the ability of the hearts to pump blood.

According to Adre Terzic, M.D., Ph.D., Mayo Clinic physician and senior author of the study, "This iPS innovation lays the groundwork for translational applications. Through advances in nuclear programming, we should be able to reverse the fate of adult cells and customize ‘on demand’ cardiovascular regenerative medicine."

However, the researchers still used dangerous viral vectors for dedifferentiation of the fibroblasts into iPS cells, even though other scientists have replaced such methods with less dangerous reprogramming techniques.

Nevertheless, according to Dr. Nelson, he believes that iPS technology will be able to be used in clinical therapies to help people, eventually, even though it might take "several years". Until then, iPS cells are still ineligible for clinical therapeutic use since there are still a number of biological hurdles remaining that have yet to be overcome.

Meanwhile, autologous adult stem cells have already been used therapeutically in the clinical treatment of heart and other conditions, and are already available in clinics around the world – except, that is, in the U.S., where outdated FDA regulations have been unable to keep pace with scientific progress.

Engineering Students Demonstrate Sutures Embedded With Adult Stem Cells

Biomedical engineering students at Johns Hopkins University have announced the successful testing of a practical method for delivering adult stem cells to a patient for the treatment of orthopedic and other types of injuries. Specifically, the undergraduate students have constructed and demonstrated a technique by which adult stem cells are embedded into the surgical thread of sutures that are routinely used in procedures to treat injuries such as ruptured tendons.

The team of students consisted of ten udergraduates who were sponsored by the Maryland-based medical technology company Bioactive Surgical Inc., and who consequently won first place for their design in the recent Design Day 2009 competition, conducted annually by the University’s Department of Biomedical Engineering. The sutures contain autologous adult stem cells, and the students have already conducted preclinical trials of the sutures in animal models, although the ultimate goal is translation of the new technology to human medical therapies.

As described on the University’s website, "In collaboration with orthopedic physicians, the students have begun testing the stem cell-bearing sutures in an animal model, paving the way for possible human trials within about five years."

According to Matt Rubashkin, the student team leader, "Using sutures that carry (autologous adult) stem cells to the injury site would not change the way surgeons repair injury, but we believe the stem cells will significantly speed up and improve the healing process. And because the stem cells will come from the patient, there should be no rejection problems."

The students’ corporate sponsor, Bioactive Surgical, developed the concept and then enlisted the student team to assemble and test the prototype during the year-long Design Team course, which is a requisite course in the Department of Biomedical Engineering. Bioactive Surgical will own the rights to the patent, which are currently pending, and a provisional patent application has also been filed which includes the improvements to the design that were made by the ten members of the Johns Hopkins undergraduate team.

In addition to demonstrating the conceptual validity of the prototype in preclinical animal testing with the assistance of orthopedic veterinarians who conducted the surgical procedures, the undergraduate team also performed a number of other related tasks which included preparing grant applications for additional funding of the technology.

Accordeing to Richard Spedden, CEO of Bioactive Surgical, "The students did a phenomenal job." Representatives of Bioactive Surgical envision a medical procedure for humans in which bone marrow would be withdrawn from the hip of a human patient under general anesthesia, from which mesenchymal stem cells would then be isolated and embedded into the novel suture through the patent-pending proprietary process, which would then be used to stitch together the ruptured tendon or other injured tissue.

In conducting their research, the students found that approximately 46,000 people every year in the U.S. alone undergo surgical repair of an Achilles tendon, which costs approximately $40,000 per surgery and can require a year or more of convalescence. As Matt Rubashkin explains, "After surgery, the recovery process can take up to a year. In about 20% of the cases, the surgery fails and another operation is needed. Anything we can do to speed up the healing and lower the failure rate and the additional medical costs could make a big difference."

According to Dr. Lew Schon, a leading foot and ankle surgeon in the greater Baltimore metroplex, one of the inventors of the technology, and an assistant professor of orthopedic surgery at the Johns Hopkins School of Medicine, "These students have demonstrated an amazing amount of initiative and leadership in all aspects of this project, including actually producing the suture and designing the ensuing mechanical, cell-based and animal trials." Additionally, he adds, "The students exceeded all expectations. They have probably cut at least a year off of the development time of this technology, and they are definitely advancing the science in this emerging area."

Grant proposals which the students prepared include further applications of the novel suture technology to other joint injuries such as rotator cuffs, and to non-orthopedic applications such as in cardiology and obstetrics.

In addition to Matt Rubashkin, the other undergraduate members of the team were David Attarzadeh, Raghav Badrinath, Kristie Charoen, Stephanie D’Souza, Hayley Osen, Frank Qin, Avik Som, Steven Su and Lawrence Wei.

Cord Blood America Highlights 2009 Stem Cell Progress

Cord Blood America Inc. (CBAI), one of the largest providers in the world of umbilical cord blood stem cell preservation, reviews its accomplishments thus far in 2009. Even though the year is only half over, CBAI considers its achievements thus far in 2009 to be among the most significant in the company’s history. Some of its accomplishments in the first half of this year are described herein.

In January: The company launched its first social media campaign in the industry to start a public conversation about the potential usefulness of adult stem cells and the importance of storing umbilical cord blood. Additionally, the company established its "3 pillars of success" for 2009, which are, namely, organic growth, acquisitions, and debt reduction for an improvement in the company’s balance sheet.

In February: CBAI was listed on the ETF Innovators Stem Cell 40 company index. Additionally, CBAI announced $1 million in long-term debt reduction as part of its cash-flow restructuring.

In March: CBAI was noted as the top stock performer on ETF Innovators Stem Cell index, with a year-to-date stock price increase of 279% at that time.

In April: Congress introduced legislation to promote the "Family Banking of Umbilical Cord Blood" stem cells, which is a major boost to the entire cord blood banking industry. Additionally, CBAI received its first customer in Germany and announced a long-term debt reduction of over $2.5 million.

In May: CBAI announced that it had received $2.3 million for the purpose of building its own stem cell processing and storage laboratory, rather than continuing to outsource the services, which thereby resulted in a further debt reduction of $4.2 million.

In June: CBAI announced further expansion throughout Europe as well as independent contracting with affilates in the Caribbean and Central America.

In July: CBAI has further secured $7.5 in long-term equity financing for acquisition and growth opportunities, while also hiring a separate management team to direct its new stem cell laboratories in the U.S., which will be among the largest in the country, construction on which has already begun.

According to Matthew Schissler, chairman and CEO of CBAI, "On January 6, 2009, the closing CBAI stock price was $0.0017. On July 10, 2009, the closing stock price was $0.0033, a 94% increase in 6 months of trading. That’s not where we want to be, we are still very undervalued, and I understand that the day-to-day swings of our very liquid and volatile stock price cause some investor concern. I tell investors to take a snapshot of the last 6 months, not six hours. Micro cap stocks are perhaps not for the faint-of-heart. We believe we’re building a very valuable company and this snapshot of the past 6 months shows our progress."

Additionally, Mr. Schissler adds, "In January, CBAI stated its mission is to lay the foundation for a much stronger, healthier company by the end of 2009, which included organic growth, acquisition and debt reduction. As you can see by these highlights, we remain laser-focused on executing these strategies. Because of our focus, we are able to raise significant funding to build a lab with the future growth opportunities it affords us. We are also pleased by the current support of stem cell research in Washington, D.C. and Congressional and state legislative focus on family stem cell banking legislation."

CBAI is the parent company of Cord Partners, which was founded in 2002 and became operational on January 1, 2003. According to the company’s website, "Cord Partners, a Cord Blood America company, has established itself as a platinum standard national competitor in the umbilical cord blood storage industry… CBAI was founded on a simple principle: The families who seek stem cell preservation should never have to work to achieve this. By bundling such services as medical kit preparation, medical courier arrangement, 24/7 customer service, easy enrollment, and one price for all services, we feel an unparalleled commitment to our clinets, and have the foundation for providing the highest quality stem cell preservation available."

Umbilical cord blood is an extremely rich source of highly potent adult stem cells, such as mesenchymal stem cells and CD34+ cells, which have already been in use for decades in the clinical treatment of various diseases, safely and without side effects. Unlike embryonic stem cells, adult stem cells derived from umbilical cord blood are ethically noncontroversial, as umbilical cord blood is easily and harmlessly collectable.

Adult Stem Cells Treat Scleroderma

Mike George, a retired junior high school principal, had been suffering from an advanced case of systemic scleroderma. Translated literally as "hard skin", scleroderma is a chronic autoimmune disease characterized by fibrosis (tightening and hardening of tissue) and for which conventional medicine has no known cure. Of the two main versions of the disease, the systemic version (also known as diffuse cutaneous scleroderma) involves internal organs as well as the skin. In the version of the disease known as limited cutaneous scleroderma, symptoms are limited primarily to the skin, although secondary complications may manifest in the pulmonary system. Vascular complications are not uncommon in the systemic version, and when one or more internal organs are affected, the disease can be fatal.

Fourteen months ago, however, Mr. George underwent autologous adult stem cell therapy as part of a clinical trial at Northwestern Memorial Hospital in Chicago. Now, according to Mr. George, "I feel really good. I feel I was reborn. It’s great to be alive."

Prior to the therapy last year, Mr. George’s skin was stiff, his face was tight, he could only swallow with difficulty, any type of physical movement was an effort, and his doctors were concerned that the disease had begun spreading to his heart and lungs. Upon his return back home after the therapy, however, Mr. George was able to lift his luggage out of the trunk of his taxi – an accomplishment which had not been possible prior to the stem cell therapy. The next month, as Mr. George describes, his physician didn’t recognize him. "In April, the doctor said, are you sure I didn’t give you a lung transplant, instead of a stem cell transplant?" Although the stem cell therapy has not totally cured Mr. George, it has stopped the progression of the disease and to some extent reversed it, with noticeable improvement not only in his skin but also in his heart and lungs as well.

On May 17, 2005, it was announced that Northwestern Memorial Hospital and the Northwestern University Feinberg School of Medicine in Chicago together launched the Northwestern Scleroderma Program, which offers patients with scleroderma a unique program of comprehensive care. According to Dr. John Varga, a rheumatologist and director of the Northwestern Scleroderma Program, "Patients who are diagnosed with scleroderma are often told that there is little that can be done for them. At Northwestern, our integrated team of experts specializes in the treatment of scleroderma and all of its related conditions. We can offer patients treatment options they can’t find elsewhere, like bone marrow transplants, while also giving them access to other important disease management services such as physical and rehabilitative therapy and nutritional counseling and support." As described on their website, "The Northwestern Scleroderma Program offers the latest advances in diagnostics and treatment for scleroderma, including bronchoscopy and lavage, high-resolution CT scanning, right heart hemodynamics (blood circulation), advanced esophageal studies, innovative treatments for pulmonary hypertension and scleroderma lung disease, as well as autologous stem cell therapies."

In fact, on this website we have previously reported a number of times in the past on various clinical studies conducted at Northwestern Memorial Hospital in which patients have shown dramatic success after having received autologous adult stem cell therapy, usually for the treatment of other types of autoimmune diseases such as multiple sclerosis. In particular, Richard Burt, M.D., Chief of the Division of Immunotherapy for Autoimmune Diseases at Northwestern Memorial Hospital, is gaining increasing attention for his pioneering use of hematopoietic stem cells in the treatment of various autoimmune diseases which include not only multiple sclerosis but also rhematoid arthritis, lupus, and Chron’s disease, among others. In 2006 Dr. Burt was named within The Scientific American 50, which is the magazine’s annual list of outstanding leaders in science and technology. According to John Rennie, editor-in-chief of the magazine, "The Scientific American 50 pays tribute to individuals and organizations who, through their efforts in research, business and policy-making, are driving advances in science and technology that lay the groundwork for a better future. Not only does our list honor these prime movers, it shines a spotlight on the critical fields that are benefiting from their achievements." Continuing his distinguished and pioneering use of autologous adult stem cell therapy, Dr. Burt is currently involved in ongoing randomized clinical trials for a number of autoimmune diseases which include systemic scleroderma.

Usually, in clinical trials, patients are neither charged nor remunerated for their participation in the trial. However, even though the scleroderma clinical trials at Northwestern are FDA-approved and tightly controlled, nevertheless Mr. George had to pay for the medical services that he received as a participant in the study, which came to more than $200,000. Family members, friends, and the communities at his church and school district helped contribute to the cost of his medical expenses.

In the study, the autologous adult stem cells were harvested from Mr. George’s own bone marrow and then readministered to him therapeutically after having been isolated, purified and expanded in the laboratory. First, however, he also received a heavy dose of chemotherapy, the purpose of which was to "cleanse" his immune system before he received his own adult stem cells, which not only served as a therapy for his scleroderma but also "rescued" his immune system from deliberate destruction by the chemotherapy. The use of chemotherapy prior to autologous adult stem cell therapy is, unfortunately, not uncommon. Fortunately, however, the scientific logic of such a routine practice is becoming increasingly questioned.

In actuality, other doctors have already demonstrated success in treating various autoimmune diseases with adult stem cell therapy, but without the brutal and deliberate destruction of the immune system with chemotherapy. Known as immunological myeloablation, such a procedure had previously been considered a necessary part of any transplant therapy, even though it exposes the patient to potentially life-threatening risks. Today, however, an increasing number of doctors are questioning the logic and necessity of subjecting their patients to deliberate immune destruction, and with valid scientific reason. In a publication that appeared over two years ago, in the Journal of Translational Medicine in January of 2007, Dr. Neil H. Riordan et al. posed the following question: "…in patients who are not suffering from a disease that is associated with an aberrant bone marrow such as hematological malignancies or immunological dysfunctions, how is it justifiable to subject them to the high levels of morbidity and mortality associated with immune suppression?" Dr. Riordan and his team of scientists then examined compelling evidence which strongly indicates that pre-transplant immune suppression is unnecessary for autologous hematopoietic cell therapies and even for some types of allogeneic therapies, such as those that utilize "universal donor" cells such as mesenchymal stem cells and the CD34+ stem cells that are found in umbilical cord blood, and for which immune rejection is not even a concern. As Dr. Riordan and his colleagues wrote in their 2007 paper in a section that is subtitled, "Mesenchymal stem cells do not need myeloablation for efficacy": "Currently there are several ongoing clinical trials in Phase I-III using ‘universal donor’ mesenchymal stem cells in non-conditioned recipients of Crohn’s disease, GVHD (graft-versus-host disease) and myocardial infarction. Although these cells are bone marrow expanded mesenchymal cells, the superior proliferative potential of cord blood mesenchymal cells may allow them not only to escape immune destruction, but also to expand in vivo and mediate therapeutic effects superior to those derived from bone marrow. The fact that regulatory agencies have allowed advancement of ‘off-the-shelf’ universal donor mesenchymal stem cells supports the numerous reports of clinical efficacy in an allogeneic setting." Therefore, certainly with autologous (in which the donor and recipient are the same person) adult stem cell therapy, there is no risk of immune rejection so there is no need to destroy the immune system with chemotherapy; but even with many types of allogeneic (in which the donor and recipient are not the same person) adult stem cell therapy, such as with "immune privileged" "universal donor" stem cells, there is also no need to destroy the immune system with chemotherapy.

Nevertheless, for clinical trials such as those conducted at Northwestern University, the autologous adult stem cell therapies offer tangible improvement – at least for those patients who survive the life-threatening destruction of their immune systems from the chemotherapy. One can only conclude, therefore, as has already been demonstrated by other doctors at other clinics, that patients would exhibit even greater and faster improvement if they did not have to recover from the deliberate destruction of their immune systems prior to receiving the stem cell therapy. Additionally, other clinical evidence indicates that even greater patient improvement would be seen if the stem cell therapy would utilize the "superior proliferative potential" of the adult stem cells that are found in umbilical cord blood.

It has been estimated that between 150,000 and 300,000 people in the U.S. alone suffer from scleroderma. Having been one of the fortunate patients who was strong enough to survive the deliberate and unncessary destruction of his immune system prior to receiving his autologous adult stem cell therapy, Mr. George is now a devout believer in autologous adult stem cells. "I’m like an advocate," he says. "All my life, I wanted to help people. Helping kids was my forte. Now to help someone in need who doesn’t know what to expect, it raises it to a whole different level."