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.