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Stem Cells and Hyperbaric Oxygen Treatment Helping with Traumatic Brain Injury

Both Hyperbaric Oxygen (HBO) treatment and Mesenchymal Stem Cells (MSC‘s) have been used as interventions for patients suffering from Traumatic Brain Injury (TBI). Though each of these therapeutic approaches can confer benefits to patients, researchers have shown that combining the two techniques can yield better results for this population of patients than either method can achieve alone. The scientists published their findings in Neural Regeneration Research earlier this year.

The transplantation of MSC‘s and the use of HBO are each effective in treating TBI for different reasons. Mesenchymal stem cells can proliferate rapidly, differentiate into many different types of cells, and do not tend to cause adverse immune reactions. While HBO treatment can enhance the brain’s aerobic metabolism, providing brain tissue with more oxygen. All of these effects are helpful after TBI has occurred. However, MSC‘s alone can be limiting in their therapeutic potential because only a fraction of those that are transplanted differentiate into mature brain cells. Because hyperbaric oxygen treatment both protects injured tissue and also supports the differentiation and migration of MSC‘s, researchers hypothesized that combining the therapies would improve lead to better neurological and cognitive outcomes following TBI than either treatment would alone.

To test their idea, the scientists induced TBI in rats to establish a rat model of the condition. They then treated one group of rats with just HBO, transplanted MSC‘s in another group of rats that did not undergo HBO, and used both interventions in a final group of rats. The researchers then looked both at physiological markers associated with TBI, as well as cognitive performance on a learning and memory task.

The results showed that rats that underwent both MSC‘s transplantation and HBO had better neurological outcomes and better cognitive performance scores than rats that endured only one type of treatment. Given these promising findings in an animal model of TBI, future research will likely address the translatability of these findings to humans. Now that a proof-of-concept exercise has been successful, there is significant support for the potential of this combination treatment regimen to help people who experience TBI.

Reference

Zhou, H. X., Liu, Z. G., Liu, X. J., & Chen, Q. X. (2016). Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury. Neural Regen Res, 11(1), 107-113. doi: 10.4103/1673-5374.175054

Long Term Study Shows Stem Cell Transplantation Helping Patients with Multiple Sclerosis

At 6 months post-treatment, neurological improvement or stabilization was observed from all (99) patients in the study except one.

In their recently published study, Long-term outcomes of autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis: physician’s and patient’s perspectives, published in the Annals of Hematology Journal, Shevchenko et al. describe the effects of an autologous hematopoietic stem cell transplantation (AHSCT) with high-dose immunosuppressive therapy (HDIT) on 99 patients with multiple sclerosis. That the stem cell transplantation is autologous means that the stem cells derive from the patient’s own body, and the stem cells being hematopoietic indicates that the stem cells give rise to blood cells.

The idea for this type of therapy for multiple sclerosis has stemmed from the fact that multiple sclerosis is characterized by nervous system inflammation. Because inflammation results from activities of the immune system, it has been thought that targeting the immune system to reduce its activity could improve symptoms of the disease. More specifically, this particular combination therapy, using AHSCT and HDIT, has been aimed at destroying the immune system and rebuilding a separate system from hematopoietic stem cells so that the new immune system functions more favorably in those with multiple sclerosis.

AHSCT and HDIT have been used in the treatment of multiple sclerosis for several years, but the specific way these techniques are able to improve multiple sclerosis is not well understood. Further, there is some debate about both the safety and effectiveness of these treatments. Small sample sizes and homogeneous patient groups have plagued many of the studies performed to address these issues. In the present study, however, the researchers studied patients with different types of multiple sclerosis. This experimental structure allowed the scientists to show that AHSCT and HDIT used in combination can help those with both remitting and progressive multiple sclerosis and that the positive effects on the disease appeared to endure over long-term periods. At 6 months post-treatment, neurological improvement or stabilization was observed from all (99) patients in the study except one. The average follow up time for patients was 62 months, or just over 5 years, and up to and at this point, 47% of patients demonstrated significant improvement jumping at least 0.5 points on the Expanded Disability Status Scale EDSS scale. These results are highly informative for physicians treating patients with multiple sclerosis and are a promising demonstration of the potential for stem cells to improve conditions like multiple sclerosis.

  • Reference
    • Shevchenko, J. L., et al. “Long-term outcomes of autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis: physician’s and patient’s perspectives.” Annals of hematology 94.7 (2015): 1149.

Stem cells from umbilical cord blood may help treat eczema

Date:

   June 7, 2016

Source:

   Wiley

Summary:

A new study suggests that treatment with stem cells from umbilical cord blood might be an effective therapy for patients with moderate-to-severe eczema, or atopic dermatitis. For the clinical trial, 34 patients were randomly assigned to receive a low dose or high dose of the cells subcutaneously. Fifty five percent of patients who received the high dose showed a 50% reduction in what’s known as the Eczema Area and Severity Index score at week 12.

A new study suggests that treatment with stem cells from umbilical cord blood might be an effective therapy for patients with moderate-to-severe eczema, or atopic dermatitis.

For the clinical trial, 34 patients were randomly assigned to receive a low dose or high dose of the cells subcutaneously.

Fifty five percent of patients who received the high dose showed a 50% reduction in what's known as the Eczema Area and Severity Index score at week 12. Immune-related markers of atopic dermatitis also decreased significantly.

"This study is a first-in-class study demonstrating that adults with moderate-to-severe atopic dermatitis responded to a treatment of stem cells derived from umbilical cord blood," said Dr. Tae-Yoon Kim, senior author of the Stem Cells study. "The single treatment of stem cells in patients resulted in the significant and persistent improvement in disease symptoms throughout the follow-up period of 12 weeks."

The study was conducted at Seoul St. Mary's Hospital in collaboration with Seoul National University (with co-senior author, Dr. Kyung-Sun Kang).

Story Source:

The above post is reprinted from materials provided by Wiley. Note: Materials may be edited for content and length.

Journal Reference:

   Hyung-Sik Kim, Ji Hyun Lee, Kyoung-Hwan Roh, Hee Jin Jun, Kyung-Sun Kang, Tae-Yoon Kim. Clinical Trial of Human Umbilical Cord Blood-derived Stem Cells for the Treatment of Moderate-to-Severe Atopic Dermatitis: Phase I/IIa Studies. STEM CELLS, 2016; DOI: 10.1002/stem.2401

Stem Cells Injected Directly Into Non-Ambulatory Stroke Patients Allows Them To Walk Again

A new study involving stem cells at Stanford has given non-ambulatory stroke patients a new lease on life by injecting stem cells directly into a non-ambulatory stroke victim’s brain. As a result, the stroke survivors showed significant improvements.

The Stanford neurosurgeon who performed 12 of the 18 stem cell procedures as part of the study, Dr. Gary Steinberg, commented on his own amazement at the success of the study.

“This wasn’t just, ‘They couldn’t move their thumb, and now they can.’ Patients who were in wheelchairs are walking now.”

However, seeing such incredible progress as a result of the stem cells may be exaggerated – not so much in the success of the sample subjects, but in the sample size itself. Such a small control group of 89 subjects could mean that the results were the product of something like a fluke or a placebo effect. What’s more, the stem cell injections didn’t mean life changing effects on all of the stroke victims.

The study at Stanford wasn’t actually intended to make wheelchair-bound individuals independently mobile again by injecting their brains with stem cells. The primary purpose of the study was primarily conducted to determine whether the injection of stem cells directly into the brain would cause any untoward side effects. However, whereas the condition of some of the non-ambulatory stroke victims bore no benefits from the injection of stem cells, there was a clear benefit to many others. Some of the stroke victims gained a minimal movement in their fingers or toes, and some were actually able to stand and walk again.

As to the stem cell test subjects, each of them had suffered a stroke at least five years before the study. This meant that each of the stroke survivors had reached what doctors perceive as the limit of how much rehabilitation or physical therapy can help them. The purpose of the stem cell study – in addition to the search for adverse side effects – was to see if stem cell injections might have some effect in helping to rebuild damaged parts of the brain. When someone has a stroke, blood flow is blocked to the brain, cutting off its oxygen and leaving parts of it highly damaged. As a result, stroke victims may have issues with speech, and physical limitations utilizing their arms and legs.

The stem cells that were used in the study were donated. They were injected into the stroke victims’ brains and targeted near the area of the brain thought to be damaged by the stroke the survivors had endured. Doctors said that as a part of the procedure, side effects included nausea, depression, and headaches. However, no further severe side effects were discovered in the initial trial. Based on stem cell injection studies in rats, stem cells are only thought to survive for about a month once they are injected into an organism. As a result of this study, though, doctors say that some of the stroke survivors that were injected with the stem cells are still improving even as much as a year after the injection.

Currently, all treatments for stroke survivors need to be utilized in the first few hours after the stroke has occurred. Clearly, that is the reason why researchers are striving so hard to figure out new ways of healing damaged parts of the brain brought on by strokes. If the stem cell injection procedure can be better understood, it may lead to new treatments that can assist stroke survivors in making full recoveries regardless of when they experienced their stroke.

The Stanford study on stem cell injections in stroke survivors in published in the journal, Stroke.


Special Report: Immunotherapies

A Brief History

Immunotherapies (biologics/cell therapies/vaccines) are among the most promising treatments in current pharmaceutical development.

What is an immunotherapy? The text book definition is the "treatment of disease by inducing, enhancing, or suppressing an immune response." Originally, the term comprised the therapeutic administration of serum or immune globulin containing preformed antibodies produced by another individual. Immunotherapy includes nonspecific systemic stimulation, active specific immunotherapy, allergen immunotherapy and adoptive immunotherapy. New forms of immunotherapy, specifically for cancer treatment, include the use of monoclonal antibodies (MAbs). Cancer immunotherapy attempts to stimulate the immune system to reject and destroy tumors.

Immuno cell therapy for cancer was first presented in the late 1980s by Rosenberg and his team at the United States, National Institutes of Health. Rosenberg reported a clinical trial in 1,205 patients with metastatic cancer who underwent different types of active specific immunotherapy. The immunotherapy regimes produced low tumor regression rates (2.6–3.3%). Rosenberg and his team thereby concluded that immuno cell therapy along with specific chemotherapy was the future of cancer immunotherapy.

The adverse effects of these initial immunotherapy products, largely cytokines such as Interleukin, sparked new techniques involving the extraction of lymphocytes from the blood and expansion in vitro against specific tumor antigens, before then injecting the cells into patients with the appropriate stimulatory (immunomodulatory, see below)) cytokines. These newly engineered cells then specifically target and destroy the tumor expressing antigen against which they have been raised.

Cell-based or adoptive immunotherapies are proven to be effective for some cancers. Immune effector cells such as lymphocytes, macrophages, dendritic cells, natural killer cells (NK Cell), cytotoxic T lymphocytes (CTL), etc, work together to defend the body against cancer by targeting abnormal antigens expressed on the surface of the tumor due to mutation.

Another promising specific and cell based immunotherapy involves the use of “loaded” specific antibodies for different types of tumor cells. These antigen specific antibodies contain either anti-neoplastic drugs or radioactive materials. When injected into the bloodstream of a patient with that particular kind of tumor, these “loaded” antibodies attach to the surface of the malignant tumor cells, thereby specifically targeting these cells and causing less damage to healthy non-malignant cells.

Non-specific immunotherapy relies on general immune stimulants to activate the whole immune system rather than specific tumor cells. In the past decade, immunotherapy against cancer has involved the use of the bacille Calmette-Guérin vaccine (bcg vaccine), which is evolved from strains of Mycobacterium tuberculosis, and is used to provide some immunity to tuberculosis.

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