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By pooling all available results from trials of bone-marrow-derived stem cells (BMSCs) in patients with ischemic heart disease or congestive heart failure, a found slight evidence to suggest a benefit for stem-cell therapy in those populations.

In pooled results from smaller randomized trials, BMSC treatment was associated with reductions in mortality (RR 0.28, 95% CI 0.14-0.53) and rehospitalization for heart failure (RR 0.26, 95% CI 0.07-0.94) at follow-up exceeding 1 year, , of NHS Blood and Transplant in Oxford, England, and colleagues reported.

But the quality of the evidence was considered low, and no significant differences were seen in those outcomes with shorter follow-up.

Multiple measures of cardiac function -- including left ventricular ejection fraction, left ventricular end-systolic volume, and stroke volume index -- and New York Heart Association class showed improvements with BMSC treatment, with moderate-quality evidence.

"At present, these results provide some evidence that stem-cell treatment may be of benefit in people both with chronic ischemic heart disease and with heart failure. Adverse events are rare, with no long-term adverse events reported," the authors wrote.

"However, the quality of the evidence is relatively low because there were few deaths and hospital readmissions in the studies, and individual study results varied," they added. "Although BMSC treatment has the potential to be used in clinical practice for people with heart failure and for those with no other treatment option, the results of this review warrant larger clinical trials to confirm the present findings."

, of the Northwestern University Feinberg School of Medicine, expressed disappointment about the results because of the low numbers of patients included in the reviewed trials, which spanned several years.

"I know these studies are difficult -- and I've been directly involved in several -- but at a certain point in time we have to call the question and say, 'Do we know anything more now, are we any closer to the clinical application of these technologies than we were a decade ago?'" he told 51成人动漫. "The answer in a very disappointing way is 'No.'"

"It doesn't mean we shouldn't continue the pursuit, but it at least points out how difficult it is, and it points out ... how unrewarding it has been up until this time," he said, adding that he remains hopeful that regenerative therapies will gain a clinical application in his lifetime.

A previous Cochrane review published in 2012 examined the use of stem-cell therapy following acute MI and showed that despite some improvements in left ventricular ejection fraction, there did not appear to be any effects on major clinical outcomes, including mortality.

But many randomized trials also have examined the potential for stem-cell treatments to improve outcomes in patients with chronic ischemic heart disease or congestive heart failure, with conflicting results.

To review the overall body of evidence, Martin-Rendon and colleagues collected data from randomized trials conducted through March 2013 that compared the use of autologous adult stem/progenitor cells with no cells/placebo. They identified 23 trials with a total of 1,137 participants diagnosed with ischemic heart disease or congestive heart failure, after excluding those with acute MI.

The average age of the patients ranged from 53 to 70, and the duration of follow-up ranged from 3 months to 5 years.

During follow-up lasting less than a year, there were no significant differences between the BMSC and control groups in mortality (RR 0.68, 95% CI 0.32-1.41) or rehospitalization for heart failure (RR 0.36, 95% CI 0.12-1.06), although an advantage for BMSC therapy did emerge over the longer term.

According to moderate-quality evidence, BMSC therapy also improved various other endpoints relative to control:

• Left ventricular end-systolic volume (mean improvement 5.47 mL in the short term and 14.64 mL in the long term)
• Stroke volume index (mean difference 3.84 in the short term and 6.52 in the long term)
• Left ventricular ejection fraction (mean difference 4.22% in the short term and 2.62% in the long term)
• New York Heart Association class (mean improvement 0.63 in the short term and 0.91 in the long term)
• Canadian Cardiovascular Society score (mean improvement 0.81 in the short term)

Subgroup analyses showed that the way the stem cells were administered, baseline ejection fraction, cell type, and the clinical status of the patients -- but not cell dose -- all influenced the observed effects, according to the authors.

Only 19 of the trials reported adverse events, and in those, only four patients had one -- one hematoma related to bone marrow harvest and three cases of pulmonary edema during injection of the cells.

But even though BMSC treatment appears to be safe and effective, the review was limited by the small size of the included studies, the low numbers of events, possible publication bias, and the large number of comparisons performed, which might have led to false-positive results.

"There is a clear need for large-scale, adequately powered studies with well-defined participant cohorts and long-term follow-up to confirm the beneficial effects of BMSC in terms of reduced mortality and rehospitalization, and improved cardiac function," the authors wrote.

They acknowledged, however, that "the potential for a large, funded clinical trial is limited, as there are no intellectual property rights associated with this procedure in its current form, rendering it unattractive to private company funding."

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