Over the past few months, we have been flooded with emails from distressed parents asking whether their deaf child will be able to hear one day.
With each new email comes a poignant story about a child whose world is silent. It is estimated that hearing loss affects 11% of school age children and even mild loss may adversely influence school performance, cognitive development and language acquisition. The most common type of hearing loss, sensorineural, is the result of injury to the hair cells of the inner ear’s Organ of Corti, most commonly due to infections, medication, noise and aging.
A digitalized image of a stem cell near hair follicles
A digitalized image of a stem cell near hair follicles
Hair cells are mechano-transducers which convert sound energy received from the outer and middle ear structures into an electrical signal which is then transmitted by the cochlear nerve to the brain. If enough of a human’s 17,000 hair cells are damaged, then sufficient sound energy cannot be transmitted to the brain, and the result is hearing loss. While birds and reptiles replace damaged hair cells, mammals normally do not.
Although hearing aids and cochlear implants, the two main treatment modalities for sensorineural hearing loss (SNHL), have helped millions with impaired hearing around the globe, these devices do not restore or repair hearing. The idea of a cure has long been a dream for many parents of deaf children and the professionals who work with them. The sad reality, however, is that SNHL is currently considered irreversible. With the emergence of regenerative medicine and stem cell therapy, however, that dream may at last be within reach.
The Food and Drug Administration (FDA) has recently approved our groundbreaking trial to evaluate the safety of using a child’s own cord blood stem cells to regenerate damaged cells in the inner ear and potentially restore the child’s hearing. This trial builds on Dr. Baumgartner’s prior success treating traumatic brain injury (TBI) with stem cells, and encouraging pre-clinical data from Italy showing that cochlear damage in mice may be repaired by transplantation of human umbilical cord hematopoietic stem cells (HSC).
In the mouse study, researchers administered HSC intravenously to a mammalian mouse model in which permanent hearing loss had been induced by ototoxic medication, noise or both. Hair cell regeneration and repair of the Organ of Corti was only observed in mice that received HSC transplants. This experiment provided a proof of concept for our trial by suggesting that under certain conditions, mammals, like birds and reptiles, could replace their damaged hair cells.
Regenerative vs Immuno-modulatory Stem Cell Therapy
There is a general misconception that stem cells exert their effect solely by differentiating into functional cell types of the exact tissue that needs replacement. For most people (and researchers) this concept frames therapeutic strategies of stem cell therapy. In reality it is too simplistic and is only partially borne out by emerging evidence. There are two broad areas of stem cell research: regenerative and immunomodulatory.
Regenerative stem cell studies attempt to utilize pluripotent (embryonic, fetal, or induced pluripotent stem cells) to create an engineered cell line which can replace damaged or defective cells. Immunomodulatory stem cell studies attempt to adjust the immune response in a way that minimizes the damage associated with the initial injury, and then allows the individual’s native repair machinery to function optimally.
Dr. Fakhri in surgery
Dr. Fakhri in surgery
With even mild injury, the immune system is activated. Macrophages are a type of immune cell which participate in the post-injury immune response. With “classic” macrophage activation, the immune response is aggressively induced. Classically activated macrophages are described as having an “M1” phenotype. In the nervous system, the M1 immune response can increase the severity of an injury. Alternatively activated or “M2” macrophages, are associated with a less destructive pattern of immune system activation. This alternate/M2 response results in less immune mediated post-injury damage, as well as the possible disinhibition of native nervous system repair.
Following traumatic brain injury (TBI) children experience a loss of 12-15% of their brain tissue in the 12 months following their injury (Levin). In a study where we treated TBI children with their own bone marrow stem cells, there was minimal post injury brain volume loss in the year after TBI (Cox). In animal models of TBI, animals that experienced injury were found to have M1 macrophages throughout their injured brain tissue.
Animals treated with stem cells after TBI were found to have M2 macrophages in their brain parenchyma. Interestingly, if an animal’s spleen was removed before stem cell infusion, the benefit of the stem cell treatment was eliminated. Somehow stem cell infusion causes a change in the pattern of macrophage activation from M1 to M2, which results in a less aggressive immune response and less post-injury brain tissue death. This effect requires an intact spleen.
After a stroke, the severity of the immune response can be predicted by measuring the size of the patient’s spleen. If the spleen loses more than 30% of its volume, the immune response will be classically activated (M1) and the extent of injury will be larger. If, however, the spleen loses less than 30% of its volume, the immune response will be less extreme, and the injury will be milder. In experimental models of stroke and traumatic brain injury, stem cells migrate to the spleen, stabilizing its volume and apparently altering the type of immune cells released from the spleen.
In the Italian mouse study mentioned earlier, the intravenous administration of HSC led to regeneration of hair cells and repair of the Organ of Corti despite the fact that only a few human-derived stem cells actually migrated into the damaged cochlea. Surprisingly, the new hair cells were generated from mouse, not human cells (Revoltella). Somehow, the cord blood treatment allowed the existing, but normally suppressed, repair process to function. The most likely mechanism for this improved repair is immune modulation.
Where do the Stem Cells Go?
Researchers have tracked the migration of stem cells administered intravenously following an injury. At first the majority of the cells lodge within the lung, where they appear to interact with pulmonary macrophages altering the type of cell signaling molecules those macrophages release into the blood. Next the stem cells migrate to the organs of the reticuloendothelial system which includes the spleen. Surprisingly, less than 3% of infused stem cells migrate into brain tissue. So the immunomodulatory effect does not require the majority of infused stem cells to interact directly with injured brain tissue.
The Neuro-Immune Response
Recent research has revealed a dynamic interaction between the nervous and immune systems. Just as stress increases heart rate and blood pressure, it also promotes a more M1 immune response. In both cases the sympathetic nervous system causes the effect. Alternatively, meditation and relaxation decrease blood pressure and heart rate and promote a more M2 type of immune response. In this case the parasympathetic nervous system appears to cause the effect (Tracey). Immunomodulatory stem cell treatments almost certainly affect this nervous system-immune system interaction.
As our research proceeds, we hope to understand this process better in order to develop better treatments for hearing loss and other conditions. Just as antibiotics changed the treatment of infections, stem cells may revolutionize the future of nervous system repair.
http://blogs.scientificamerican.com/gue ... its-parts/
Groundbreaking Clinical Trial to Treat Hearing Loss with Cord Blood Stem Cells
Children's Memorial Hermann Hospital (UTHealth) and Cord Blood Registry are launching the first FDA-approved study of the use of cord blood stem cells to treat children with sensorineural hearing loss.
The study, which will use the patients’ own stored umbilical cord blood stem cells, is the first of its kind with the potential to restore normal hearing. It follows the publication of promising preclinical data and several ongoing trials evaluating autologous cord blood infusions in novel cellular regenerative therapies.14
The year-long study will follow 10 children, aged 6 weeks to 18 months, who have sustained a post-birth hearing loss. To ensure consistency in cord blood stem cell quality, CBR is the only stem cell bank whose clients can participate in the study. This study is exciting because it might offer a non-surgical option for some children with profound loss. Researchers hope that this study will open avenues to additional treatment options for hearing loss in children.
http://www.cordblood.com/stem-cell-rese ... aring-loss
Korte vertaling: Bij muizen is men er in geslaagd om het gehoor te herstellen door het gebruik van stamcellen.Stem cells used to regenerate hearing
For the first time, doctors are using stem cells to regenerate hearing in young children who acquire hearing loss. We spoke to the only child to receive the treatment so far to find out how she's progressing.
When Stephanie Connor was pregnant with her daughter Madeline, she was infected with CMV – a herpes virus which causes development disabilities and hearing loss in babies.
"I figured she would be deaf," Connor said.
While she did lose her hearing, Connor says her now two-year-old daughter's hearing is improving thanks to an FDA approved study which uses umbilical cord blood to restore hearing.
"When I found out how badly off she was it was the only thing I could think of to help her," Connor said.
The year long study will follow 10 children ages six weeks to 18 months who have sustained an acquired hearing loss – meaning it isn't genetic - and who have registered with the cord blood registry.
"Be an opportunity with this treatment to reverse some of the damage and maybe even repair it to make these people better," said the study sponsor Dr. James Baumgartner.
Dr. Baumgartner is the sponsor of the study out of Children's Memorial Hermann Hospital in Texas.
He says he believes this safe and effective treatment will allow children to hear well enough to acquire normal speech.
"Giving cord blood back is a lot like someone's own blood transfusion - it's very safe," he said.
Since this study is in the very early stages, doctors don't know yet what effect it will have on Madeline.
But since January, she's started speaking.
"It's definitely worth a shot to give her the ability to hear and speak," Connor said.
Hopefully, she says, Madeline will be making even more progress as the months go on.
Her next check up is in July.
http://www.abc-7.com/story/18610064/ste ... te-hearing
Nu zijn er onderzoeken bezig met jonge kinderen die aan gehoorschade lijden. Door stamcellen te gebruiken hoopt men hun gehoor te herstellen, de eerste resultaten zijn voorzichtig positief.
Het artikel vermeldt niets over Tinnitus of Hyperacusis, maar mij lijkt dat herstel van het gehoor ook leidt tot genezing hiervan, of het zal op zijn minst een belangrijke stap voorwaarts zijn!