‏إظهار الرسائل ذات التسميات Stem Cell Therapy. إظهار كافة الرسائل
‏إظهار الرسائل ذات التسميات Stem Cell Therapy. إظهار كافة الرسائل

الجمعة، 7 ديسمبر 2012

Stem cell treatment for acute myocardial infarction

Stem cell treatment for acute myocardial infarction

  1. David M Clifford2,
  2. Sheila A Fisher3,
  3. Susan J Brunskill3,
  4. Carolyn Doree3,
  5. Anthony Mathur4,
  6. Suzanne Watt5,
  7. Enca Martin-Rendon1,*
Editorial Group: Cochrane Heart Group
Published Online: 15 FEB 2012
Assessed as up-to-date: 23 JUL 2011
DOI: 10.1002/14651858.CD006536.pub3

Background

Stem cell therapy offers a promising approach to the regeneration of damaged vascular and cardiac tissue after acute myocardial infarction (AMI). This has resulted in multiple randomised controlled trials (RCTs) worldwide.

Objectives

To critically evaluate evidence from RCTs on the effectiveness of adult bone marrow-derived stem cells (BMSC) to treat acute myocardial infarction (AMI).

Search methods

This Cochrane review is an update of a previous one (published in 2008). MEDLINE (1950 to January 2011), EMBASE (1974 to January 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2011), CINAHL (1982 to January 2011) and the Transfusion Evidence Library (1980 to January 2011) were searched. In addition, several international and ongoing trial databases were searched and handsearching of relevant conference proceedings undertaken to January 2011.

Selection criteria

RCTs comparing autologous stem/progenitor cells with no autologous stem/progenitor cells in patients diagnosed with AMI were eligible.

Data collection and analysis

Two authors independently screened all references, assessed trial quality and extracted data. Meta-analyses using a random-effects model were conducted and heterogeneity was explored for the primary outcome using sub-group analyses.

Main results

Thirty-three RCTs (1765 participants) were eligible for inclusion. Stem/progenitor cell treatment was not associated with statistically significant changes in the incidence of mortality (RR 0.70, 95% CI 0.40 to 1.21) or morbidity (the latter measured by re-infarction, hospital re-admission, restenosis and target vessel revascularisation). A considerably high degree of heterogeneity has been observed among the included trials. In short-term follow up, stem cell treatment was observed to improve left ventricular ejection fraction (LVEF) significantly (WMD 2.87, 95% CI 2.00 to 3.73). This improvement in LVEF was maintained over long-term follow up of 12 to 61 months (WMD 3.75, 95% CI 2.57 to 4.93). With certain measurements and at certain times, stem cell treatment was observed to reduce left ventricular end systolic and end diastolic volumes (LVESV & LVEDV) and infarct size significantly in long-term follow up. There was a positive correlation between mononuclear cell dose infused and the effect on LVEF measured by magnetic resonance imaging. A correlation between timing of stem cell treatment and effect on LVEF measured by left ventricular angiography was also observed.

Authors' conclusions

Despite the high degree of heterogeneity observed, the results of this systematic review suggest that moderate improvement in global heart function is significant and sustained long-term. However, because mortality rates after successful revascularization of the culprit arteries are very low, larger number of participants would be required to assess the full clinical effect of this treatment. Standardisation of methodology, cell dosing and cell product formulation, timing of cell transplantation and patient selection may also be required in order to reduce the substantial heterogeneity observed among the included studies.
 

Plain language summary

Stem cell treatment following a heart attack

Currently the standard treatment for people suffering a heart attack (due to a blockage in the artery supplying blood to the heart) is to directly open the artery with a tiny balloon in a procedure called primary angioplasty and to introduce a small tube into the artery to keep it open called a stent. The use of primary angioplasty and stents to reopen the blocked artery can lead to a 33% reduction in the mortality (death rate) associated with this condition. Recently, bone marrow stem/progenitor cells have been investigated as a new treatment that may prevent the damage to heart muscle caused by a heart attack in addition to the treatment offered by primary angioplasty. Analysis of randomised controlled trials to 2011 indicates that this new treatment may lead to some improvements over standard treatment as measured by tests of heart function in the short and long term. Over 1,700 patients have participated so far in the 33 trials included in this systematic review.
 

Stem Cell Therapy May Fix Defects From Injuries To Head And Mouth

Researchers have discovered, in the first human study of its kind, that it is faster, more effective and less invasive using stem cells to re-grow craniofacial tissues, i.e. mainly bone, compared with traditional bone regeneration treatments.

The clinical trial was a collaboration of researchers from the University of Michigan School of Dentistry and the Michigan Center for Oral Health Research together with Ann Arbor-based Aastrom Biosciences Inc. involving 24 patients who required jawbone reconstruction after tooth removal. The researchers divided the patients into two groups, with one group receiving experimental tissue repair cells (ixmyelocel-T) and the other group receiving traditional guided bone regeneration therapy. The tissue repair cells ixmyelocel-T are currently being development at Aastrom.

Leading investigator Darnell Kaigler, who is assistant professor at the U-M School of Dentistry said:


"In patients with jawbone deficiencies who also have missing teeth, it is very difficult to replace the missing teeth so that they look and function naturally. This technology and approach could potentially be used to restore areas of bone loss so that missing teeth can be replaced with dental implants."


Kaigler stated that the treatment is best suited for large defects, like those resulting from trauma, diseases or birth defects, since these are very challenging to treat due to their complex nature of requiring various different tissue types, including bone, skin and gum tissue.

He continued saying that the key advantage of using stem cell therapy is that the patient's own cells are used to regenerate tissue instead of using man-made, foreign materials.

The study achieved promising results. Study participants in the cell therapy group received dental implants at 6 and 12 weeks after their experimental cell therapy and were noted to have a greater bone density and quicker bone repair compared with those who underwent traditional guided bone regeneration therapy. They also needed less secondary bone grafting when receiving their implants compared with the traditional bone regeneration group.

The team used cells extracted from the patient's hip bone marrow, which was subsequently processed using Aastrom's proprietary system. This allows the growths of many different cells, including stem cells, which were then relocated into different areas in the patient's mouth and jaw.

Kaigler concluded saying that stem cell therapies are still probably 5-10 years away from becoming a standard treatment for oral and facial injuries and defects and that more clinical trials need to be conducted, which include a larger number of patients with larger craniofacial defects.

Written by Petra Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Stem Cell Therapy Only Works With Younger Hearts


A new study by researchers at Cornell University and the University of Bonn has found that even though stem cells can actually replace dead heart tissue after a heart attack very early in life, those same cells lose regenerative ability in adults.

The researchers, using mice as their subjects, came to the conclusion that undifferentiated precursor cells grow new heart cells in a two-day-old mouse, but not in adult mice. This finding settled a decades-old debate whether or not stem cells can play a role in the recovery of the adult mammalian heart after infarction (when heart tissue dies due to a local lack of oxygen).

Stem cells are biological cells found in all multicellular organisms. They are characterized by the ability to divide through mitosis and differentiate into diverse specialized cell types. They can self-renew to produce more stem cells.

Michael Kotlikoff, dean of Cornell's College of Veterinary Medicine and senior author of the paper that will appear August 29th in the Proceedings of the National Academy of Sciences, said:


"While the existence of these cells in adults is controversial, if one did have fully capable stem cells in adults, why are there no new heart cells after an infarct? Whether this is due to a lack of stem cells or to something special about the infarct that inhibits stem cells from forming new heart cells is the question we addressed, taking advantage of the fact that the newborn mouse has these new cells."


According to Kotlikoff and team, the two-day old mice were able to grow new heart cells and almost completely recover from infarction, which proved that the injury did not stop stem cells from growing new heart cells. The results also showed that adults do not have the requisite stem cells to create new heart cells, called myocytes, because when when the same procedure was carried out on them, no new heart cells formed. However, new blood vessels were created.

Kotlikoff explained that the stem cells in the adult heart "have lost the ability to become heart cells, and are only capable of forming new vessels." At the start of life, single stem cells differentiate into all tissues, but as time goes on these cells become "developmentally restricted" or specialized to form only certain tissues.

Written by Sarah Glynn
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Using Stem Cell Therapy For Neck And Head Cancers Avoids Salivary Gland Damage Caused By Radiotherapy

Approximately 40% of individuals treated for head and neck cancer experience the distressing adverse-effects of dry mouth syndrome. However, researchers in the Netherlands may have found a way to prevent impairing salivary glands during radiotherapy treatment.

The researchers note this finding could enhance the quality of life of 500,000 individuals with head and neck cancer each year worldwide.

The team found that the stem cells needed for regenerating the parotid gland (the largest pair of salivary glands) were primarily located in the major ducts of the gland. According to the researchers, these cells could be easily avoided during radiotherapy or given a minimal radiation dose.

Dr. Peter van Luijk, a research associate at the University Medical Center Groningen, The Netherlands, explained:

"This would significantly reduce complications arising from radiotherapy for head and neck cancer."


Findings from the study were presented at the 31st conference of the European Society for Radiotherapy and Oncology (ESTRO31).

Dry mouth syndrome is a condition in which there is not enough saliva in the mouth. The condition can occur when the parotid gland stops functioning properly after radiation damage.

Symptoms of dry mouth syndrome include difficulty sleeping, eating, tooth decay or loss, and bad breath. These symptoms lead to poorer quality of life and difficulty working, as well as social isolation.

The majority of treatments to treat the condition and its consequences are insufficient and can cost hundreds or even thousands of Euros per patient each year.

Dr. van Luijk said:

"Parotid gland dysfunction after radiotherapy for head and neck cancer was, and still is, a major clinical problem. During radiotherapy, attempts to minimize the risk of this complication have been aimed at reducing the average dose to the salivary gland, on the assumption that it would not make a difference where in the gland the radiation dose was reduced.

However, this does not seem logical according to the anatomy of the salivary gland and, in previous work, we discovered that reductions in radiotherapy dose to some parts of the gland allowed the parotid gland to regenerate, whereas a dose to other parts did not.

Therefore, we decided to investigate the reason for these regional differences. We hypothesized that our observations could be explained by a non-uniform distribution of stem cells necessary for the long-term maintenance of organ function and affected by irradiation."

The team first used rodent (mouse & rat) models in order to research the location of stem cells and the effects of radiotherapy to specific regions of the gland. They then examined parotid and salivary gland tissue taken from individuals undergoing a neck dissection for head and neck cancer.

In both the rodent models and human tissue, the team found that the stem cells were mainly located in the major ducts of the parotid gland. Dr. van Luijk explained:

"We have found in previous work that these stem cells are capable of regenerating a parotid gland when they have been transplanted after irradiation."


After dissecting the parotid gland of the rat and culturing various parts of the gland in Petri dishes, the researchers found that an abundant concentration of stem cells were located in the center of the gland where the major ducts are located.

The team then directed high-precision irradiating to the center of the gland in living rats and discovered that it caused saliva production to decrease significantly, in contrast to the minimal effects seen after irradiating other regions of the gland.

Dr. van Luijk said:

"The position of the stem cells in rats corresponds to the cranio-ventral extension of the gland in humans, where the excretory duct leaves the gland on the ventral, or outward-facing side. So even though the glands have different shapes in rats and humans, the stem cells are in the exact same anatomical structure."


The team then created a mathematical model based on the treatment of 36 patients in order to test their theory. This model allowed them to estimate the expected parotid gland function depending on the stem cell dose.

Dr. van Luijk explained:

"Excitingly, dose to the cranio-ventral extension of the gland containing the major ducts was most predictive of damage to saliva production. In addition, we found that it was possible to reduce the dose by approximately 50% to this part of the gland, without increasing the average dose to the whole gland or the dose to other critical structures in the head and neck region, and without compromising adequate target coverage.

Using the mathematical model, we estimated that with such dose reduction none of the patients would have developed parotid gland dysfunction. This is, however, a hypothesis that needs to be tested prospectively in a randomized clinical trial by comparing parotid gland function in a group of patients treated with current standard to a group in which, additionally, the dose to the stem cells is minimized using our proposed stem cell sparing technique. This technique should only be implemented in radiotherapy clinics when such a trial proves there is a benefit as predicted by our research."


Dr. van Luijk continued:

"Our findings can be seen as a proof-of-principle that elucidation of biological mechanisms in complications may lead to the identification of critical sub-structures of organs, possibly leading to new opportunities to reduce harm to normal tissue. Though we only show this for the parotid gland, such approach may apply to other organs as well."


According to the team it is easy to avoid the gland during radiotherapy.

Dr. van Luijk said:

"The stem cell region is on the side of the gland that is normally furthest away from the target area containing the tumor cells. Since only this area needs a high radiation dose, this distance makes avoiding the stem cell area easier than avoiding other parts of the gland.

Based on our results we hypothesize that sparing the parotid gland stem cell region, costing around €100 in extra man-hours, may effectively prevent salivary gland dysfunction. This will allow patients to more readily lead their normal lives without having to rely upon medical care and welfare."


He concluded:

"Maybe even more importantly, cancer patients will remain productive members of society, realizing a cost reduction far beyond the cost of medication. Finally, it will improve quality of life of 500,000 patients treated with radiotherapy for head and neck cancer worldwide every year."


Professor Bradly G. Wouters, Ph.D., a radiobiologist at the Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada, and chair of the conference radiobiology track, said:

"This is an exciting clinical study that has identified a critical region of the salivary gland that contains stem cells that can regenerate the gland and preserve function in patients with head and neck cancer.

Using advanced radiation techniques the investigators show it is possible to spare this region and thus deliver higher therapeutic doses without causing more toxicity to patients."

Written By Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Huntington's Disease - Stem Cell Therapy Potential


At present there is no effective treatment for Huntington's disease - a progressive disorder in which nerve cells in certain parts of the brain waste away or degenerate and affects muscle coordination.

However, according to a study published March 15 in the journal Cell Stem Cell, a special type of brain cell created from stem cells could help restore the muscle coordination deficits that are responsible for uncontrollable spasms, a characteristic of the disease. The researchers demonstrated that movement in mice with a Huntington's-like condition could be restored.

Su-Chun Zhang, a University of Wisconsin-Madison neuroscientist and the senior author of the study, said:


"This is really something
unexpected."


In the study Zhang, who is an expert in creating various types of brain cells from human embryonic or induce pluripotent stem cells, and his team focused on GABA neurons. The degradation of GABA cells causes the breakdown of a vital neural circuit and loss of motor function in individuals suffering from Huntington's disease.

According to Zhang, GABA neurons generate a vital neurotransmitter, a chemical that helps support the communication network in the brain that coordinates movement.

Zhang and his team at the UW-Madison Waisman Center, discovered how to generate large quantities of GABA neurons from human embryonic stem cells. The team's goal was to determine whether these cells would safely integrate into the brain of a mouse model of Huntington's disease.

The researchers discovered that not only did the cells integrate, they were projected to the right target and were able to effectively restore the damaged communication network and restore motor function.

Zhang says that the results were astonishing, as GABA neurons reside in the basal ganglia, a part of the brain which plays a vital role in voluntary motor coordination. However, the GABA neurons exert their influence at a distance on cells in the midbrain via the circuit powered by the GABA neuron chemical neurotransmitter.

Zhang, explained:

"This circuitry is essential for motor coordination and it is what is broken in Huntington patients. The GABA neurons exert their influence at a distance through this circuit. Their cell targets are far away.

Many in the field feel that successful cell transplants would be impossible because it would require rebuilding the circuitry. But what we've shown is that the GABA neurons can remake the circuitry and produce the right neurotransmitter."


The findings from the study are vital as they indicate that cell therapy may be used in the future to treat Huntington's disease, and they also indicate that the adult brain may be more malleable than they previously thought.

Neuroscientists believe that the adult brain is stable and not easily receptive to treatments that aim to fix things, such as destroyed circuits at the root of diseases like Huntington's. In order for a treatment to work, it has to be created so that only the cells of interest are affected.

Zhang, said:

"The brain is wired in such a precise way that if a neuron projects the wrong way,
it could be chaotic."


According to Zhang, although the new study holds promise, it will take a considerable amount of time and effort in order to work up from the mouse model to human patients. However, as there is currently no effective treatment for the disease, the work could become the best hope for individuals suffering with Huntington's.

The study was supported by the U.S. National Institutes of Health and the Chinese Ministry of Science and Technology.

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today