Low level laser treatment of bone marrow helps heal hearts after a heart attack

A fascinating paper published in the journal Lasers in Surgery and Medicine shows that low-level laser treatment of bone marrow can have profound effects on the ability of bone marrow stem cells to repair a heart after a heart attack.

The paper’s authors are H Tuby, L Maltz, and Uri Oron, who are members of the Zoology department at Tel-Aviv University, Tel-Aviv, Israel. The title of the paper is “Induction of autologous mesenchymal stem cells in the bone marrow by low-level laser therapy has profound beneficial effects on the infarcted rat heart,” and it was published in the July edition of Lasers in Surgery and Medicine, 2001;43(5):401-109.

Oron and his co-workers have been studying the effects of photobiostimulation with low-level lasers on injured tissues. Their recent work established that application of low energy laser irradiation (LELI) to the site of injury in muscles, bone marrow or heart is beneficial. This irradiation does not heat the tissue and has not been found to cause adverse side effects.

The strategy of this study is rather simple: LELI on bone marrow stem cells after an laboratory animal has suffered a heart attack. The stimulated bone marrow stem cells might migrate to the injured heart and repair it. They used Sprague-Dawley rats, and induced heart attacks in those rats. Then they subjected the bone marrow of those rats to LELI 20 minutes or four hours after the heart attack. They also had rats that had not experienced heart attacks but were operated on as controls, and rats that had suffered heart attacks but were not treated with LELI. For those interested, they used a Ga-Al-As diode laser, power density 10 mW/cm², for 100 seconds.

The results were astounding. The size of the infarction was reduced by 75% and dilation of the ventricle was reduced 75% in those animals treated with LELI 20 minutes after the heart attack. There was also a 25-fold increase in the density of bone marrow-derived cells in the heart relative to the non-LELI-treated controls. This indicates that LELI offers a new approach to induce bone marrow stem cells to move into the blood stream, arrive at the damaged heart and repair it. This mobilization of bone marrow stem cells great shrinks the scar caused by a heart attack in laboratory animals. Maybe it’s time for trials in larger animals and then a phase I clinical trial in humans?

Phase I Study of Embryonic Stem Cell-Derived Retinal Pigment Epithelium Cells Shows Early Signs of Success

Several different diseases cause deterioration of the eye and plunge aging or even young men and women into a life of blindness. Several of these genetic diseases affect the tissues that reside at the back of the eye, which is collectively called the retina. The retina contains two main layers; an inner neural retina and an outer pigmented retina.

The neural retina is filled with photoreceptors and cells that process the outputs from the photoreceptor cells and send them to the brain. The pigmental retina contains the retinal pigmented epithelium, which plays a central role in retinal physiology. The retinal pigmented epithelium or RPE forms the outer blood-retinal barrier and supports the function of the photoreceptors. Many diseases the adversely affect the retina called “retinopathies” involve a disruption of the epithelium’s interactions with the neural retina. Other types of retinopathies are caused by uncontrolled proliferation of the RPE cells.

Transplantation of RPE cells can help treat patients that have various types of retinopathies (see Lund RD et al.,Cloning Stem Cells.2006 Fall;8(3):189-99).  However, embryonic stem cells can be made into copious quantities of RPEs rather easily (Huang Y, Enzmann V, Ildstad ST. Stem Cell Rev. 2011 Jun;7(2):434-45).  Therefore, it was only a matter of time before clinical trials were instigated with embryonic stem cell-derived RPEs.

In recent edition of the journal The Lancet, Steven Schwartz and colleagues have reported the first clinical results from patients treated with embryonic stem cell-derived RPEs.  A patient with “Stargardt’s macular dystrophy,” which is the most common form of pediatric macular degeneration, and a patient with dry age-related macular degeneration, the leading cause of blindness in the developed world, each received a subretinal injection of RPEs derived from embryonic stem cells (ESCs).  Both of these disorders are not treatable at present, but both also result from degeneration of the RPE.  Loss of RPE cells causes photoreceptor loss and progressive vision deficiency.

Schwartz and colleagues differentiated the hESCs into RPE cultures that showed greater than 99% purity.  Then they injected 50,000 RPE cells into the subretinal space of one eye in each patient. Each patient received anti-rejection drugs (low-dose tacrolimus and mycophenolate mofetil) just in case the immune system tried to attack the transplanted RPE cells.

There results are hopeful, since, after 4 months, both patients show no sign of retinal detachment, hyperproliferation, abnormal growths, intraocular inflammation, or teratoma formation.  Anatomical evidence of the injected cells was difficult to confirm in the patient with age-related macular degeneration, but was present in the patient with Stargardt’s macular dystrophy.

Both patients showed some visual improvements.  The patient who suffers from age-related macular degeneration improved in visual acuity, since she was able to recognize 28 letters in a visual acuity chart, whereas before he procedure, she was able to identify only 28 (improvement from 20/500 vision to 20/320).  The patient with Stargardt’s macular dystrophy went from counting fingers and seeing only one letter in the eye chart by week 2, and to a stable level of five letters (20/800) after 4 weeks.  This patient also showed subjective improvement in color vision, contrast, and dark adaptation in the treated eye.

These results are highly preliminary and the improvements are slight, but the progressive nature of these eye diseases suggests that the injections largely worked.  Before we can crack our knuckles for joy, we will need to see improvements with more than two patients.  But the fact that the treated eye showed improvements not seen in the untreated eye is highly suggestive that the transplanted RPEs are improving the health of the photoreceptors in the neural retina.  The eye is an ideal place to do such research because it is one place in the body that is not regularly patrolled by the immune system, and foreign cells placed in the eye tend to receive far less scrutiny from the immune system than other parts of the body.

I am glad for these patients, but I am troubled by this experiment.  Other types of stem cells can be converted into RPEs (Uygun BE, Sharma N, Yarmush M. Crit Rev Biomed Eng. 2009;37(4-5):355-75.).  Also, there are other stem cells in the eye that, if properly investigated might possess the ability to form RPEs (Bhatia B, et al.,Exp Eye Res. 2011 Dec;93(6):852-61).  Why was this experiment first done with cells that require the death of early human embryos?  The safety concerns with ESCs makes the clinical trial far more expensive and slower.  While the embryos sacrificed to make these RPEs have long since died, the ESC culture is doing some clinical good.  However, how would we feel about cell lines made from children who were murdered by a sadistic scientist?  Would you receive treatments from them given what you know about their origin?  So while this experiment shows hope, it also leads to controversy as well that is not being discussed as deeply as it should.

NBC’s The Doctors to Feature Centeno Clinic and Regenexx Stem Cell Procedures on Wednesday, January 25, 2012

Tomorrow (Wednesday, January 25th, 2012), the popular TV show “The Doctors” will feature the Centeno/Schultz clinic and their orthopedic stem cell treatment known as “Regenexx.” On hand will be Dr. Hanson from the Centeno clinic (unfortunately Dr. Centeno was in China for the studio taping), and a former Regenexx patient named Barbee James. Ms. James had knee cartilage breaks and received the Regenexx-C knee stem cell procedure in 2008. The stem cell-treated knee is doing quite well, but the other knee, which was surgically treated with a failed micro fracture procedure, is now in need of a stem cell treatment. See a preview of the show here.

Rick Santorum Defends Life in the Wall Street Journal

Republican presidential candidate Rick Santorum has written another eloquent defense of human life at all stages of development. This is in the form of an op-ed piece that was published at the Wall Street Journal. Unfortunately, you need a subscription to the newspaper to read it here.  Fortunately, Santorum has a free copy of it on his Twitter page here.

Our country’s Declaration of Independence stated: “We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness.–That to secure these rights, Governments are instituted among Men, deriving their just powers from the consent of the governed.”  Unfortunately, we did not live by those words consistently when our fore-bearers agreed to let some enslave their African brothers.  Nevertheless, if the principles of freedom are morally praiseworthy, they must apply to all of us no matter what our age.

Umbilical cord stem cells form nervous system-specific cells for spinal cord repair therapies

Umbilical cord stem cells (UCSCs) have been differentiated into clinically significant cell types that might, potentially, lead to new treatment options for spinal cord injuries, multiple sclerosis, and other nervous system diseases.

James Hickman, a University of Central Florida bioengineer and leader of the research group that accomplished this work, said, “This is the first time this has been done with non-embryonic stem cells. . . . We’re very excited about where this could lead because it overcomes many of the obstacles present with embryonic stem cells.” Hickman’s work and that of his colleagues was published in the Jan. 18 issue of the journal ACS Chemical Neuroscience.

UCSCs do not pose the ethical dilemma represented by embryonic stem cells (ESCs). ESC lines are made from 5-day old human embryos and in order to derive them, the inner cell mass cells are extracted from the embryo by means of destroying the embryo. Destruction of a human embryo ends the life of a very young human person. UCSCs, however, come from a source that would otherwise be discarded, and the acquisition of UCSCs do not compromise the life of a human person. Another major benefit is that umbilical cells generally are not rejected by the immune system, and this simplifies their potential use in medical treatments.

The Menlo, California-based pharmaceutical company, Geron, developed a treatment protocol for spinal cord repair that utilized oligodendrocyte precursor cells that were derived from embryonic stem cells. However, it took Geron scientists 18 months to secure approval from the Food & Drug Administration (FDA) for human clinical trials. This is due, largely, to the ethical and public concerns attached to human ESCs. These concerns, in addition to anxieties over ESC-caused tumors, led the company to shut down its ESC division. This highlights the need for other stem cell alternatives.

One of the greatest challenges in working with any kind of stem cell is determining the precise chemical or biological cues that trigger them to differentiate into the desired cell type.  The lead author on this paper, Hedvika Davis, a postdoctoral researcher in Hickman’s lab, transformed UCSCs into oligodendrocytes (those structural cells that surround and insulate nerves in the brain and spinal cord). Davis learned from research done by other groups that surface proteins on the surfaces of oligodendrocytes bind the hormone/neurotransmitter norepinephrine. This suggests that cells normally interact with this chemical and that it might be one of the factors that stimulates oligodendrocyte production. Therefore Davis decided to treat USCSs with epinephrine as a starting point.

In early tests, Davis found that norepinephrine, plus several other stem cell growth promoters, caused the UCSCs to differentiate into oligodendrocytes. However, that conversion was incomplete, since the cells grew but stopped short of becoming completely mature oligodendrocytes. Clearly something else was needed to push UCSCs completely into mature oligodendrocytes.

Many stem cells differentiate into particular cell types only if the appropriate environment is offered to them. For example, mesenchymal stem cells can form cartilage, but cartilage formation is extremely sensitive to environmental factors like cell density, and the matrix in which cells are embedded. Thus, Davis decided that, in addition to chemistry, the physical environment might be critical. In order to more closely approximate the physical restrictions cells face in the body, Davis constructed a more confined, three-dimensional environment. She grew the cells on a microscope slide, covered by a glass cover slip. Once the UCSCs had the proper confined environment and norepinephrine plus the appropriate growth factors, they differentiated into completely mature oligodendrocytes. Davis noted, “We realized that the stem cells are very sensitive to environmental conditions.”

The use of these differentiated oligodendrocytes is exciting. There are two main options for the use of these cells. First, the cells could be injected into the body at the point of a spinal cord injury to promote repair. Another intriguing possibility for the Hickman team’s work relates to multiple sclerosis and similar conditions. Hickman explained, “Multiple sclerosis is one of the holy grails for this kind of research.” Hickman’s research group is collaborating with Stephen Lambert at UCF’s medical school, another of the paper’s authors, to explore biomedical possibilities.

Oligodendrocytes produce a protein called myelin, which insulates nerve cells. Myelin sheaths make is possible for neurons in the central nervous system to conduct those nerve impulses that guide movement and other functions. Myelin loss is responsible for conditions like multiple sclerosis, and is also observed in other related conditions such as diabetic neuropathy.

The injection of new, healthy oligodendrocytes might improve the condition of patients suffering from such neurological diseases. These research teams are also hoping to develop the techniques needed to grow oligodendrocytes in the lab and use them a model system to better understand the loss and restoration of myelin, and for testing potential new treatments. Hickman enthusiastically said, “We want to do both. We want to use a model system to understand what’s going on and also to look for possible therapies to repair some of the damage, and we think there is great potential in both directions.”

Canadian Legislature Wants to Ban Sex-Selection Abortions

Wesley Smith at his blog “Secondhand Smoke” has an excellent article on the Canadian Medical Association Journal‘s proposal to ban disclosing the sex of a baby to the parents, until the baby is 30 weeks old. This proposal is hypocritical, since the CMAJ has no problem with abortion for purposes of eugenics, in vitro fertilization, or lifestyle choices. In all those cases, at least 50% of the babies whose lives are terminated are female, but for some reason, CMAJ thinks that termination of a female baby’s life just because the parents want a boy rather than a girl is illicit. The journal even calls it “feticide.”

Well, so now abortion is feticide. That’s what I’ve been saying all along. Read Smith’s article here.

BrainStorm Announces that There Are No Dangerous Side Effects Observed in NurOwn Trial

A developer of innovative stem cell technologies, BrainStorm Cell Therapeutics Inc. has developed a stem cell treatment called NurOwn for central nervous system-based disorders. NurOwn™ is a product derived from human bone marrow mesenchymal stem cells. After these cells are collected from a patient by means of a bone marrow aspiration (which not nearly as invasive as a bone marrow biopsy), they are differentiated into nerve-like cells that can release the neurotransmitter dopamine and a nervous system-specific growth factor called glial-derived neurotrophic factor (GDNF). Dopamine cell damage and death is the hallmark of Parkinson’s Disease (PD), and GDNF-producing cells can protect healthy dopamine-producing cells and repair degenerated cells. This halts the progression of PD and other neurodegenerative diseases. BrainStorm’s NurOwn™ therapy for PD replaces degenerated dopamine-producing nerve cells and strengthens them with GDNF.

BrainStorm has just announced patient data from its ALS combined phase I & II human clinical trial. ALS patients who were treated with NurOwn, a stem cell-based product that BrainStorm had developed, did not show any significant side effects to the NurOwn treatment. Therefore, so far, NurOwn seems to be safe.

The leader of this clinical trial at Hadassah Medical Center, Prof. Dimitrios Karussis, stated, “There have been no significant side effects in the initial patients we have treated with BrainStorm’s NurOwn technology. In addition, even though we are conducting a safety trial, the early clinical follow-up of the patients treated with the stem cells shows indications of beneficial clinical effects, such as an improvement in breathing and swallowing ability as well as in muscular power. I am very excited about the safety results, as well as these indications of efficacy, we are seeing. This may represent the biggest hope in this field of degenerative diseases, like ALS.”

The Hadassah Medical Center ethics committee reviewed the safety data from the first four patients who were implanted with NurOwnTM, and concluded that the clinical trial should proceed with implanting the next group of ALS patients.

BrainStorm’s President, Chaim Lebovits, remarked: “We are happy to report that the first patients treated with our NurOwn technology did not present any significant side effects. This supports and strengthens our belief and trust in our technology. Based on the interim safety report, the hospital ethical and safety committee granted the company approval to proceed with treating the next patients. We are pleased with the progress we are making and look forward to continuing to demonstrate the safety of NurOwn in the future.”

This study is headed by Prof. Karussis, MD, PhD, head of Hadassah’s Multiple Sclerosis Center and a member of the International Steering Committees for Bone Marrow and Mesenchymal Stem Cells Transplantation in Multiple Sclerosis (MS), and a scientific team from BrainStorm headed by Prof. Eldad Melamed. This clinical trial is being conducted at Hadassah Medical Center in Israel in collaboration with BrainStorm and utilizes BrainStorm’s NurOwn technology for growing and modifying autologous adult human stem cells to treat ALS, which is often referred to as Lou Gehrig’s Disease. The initial phase of the study is designed to establish the safety of NurOwn, but will also be expanded later to assess efficacy of the treatment.