BMSC (Ever Supreme)

A promising approach to the treatment of chronic ischaemic heart disease (IHD) and heart failure is the use of stem cells. The last decade has seen a plethora of randomised controlled trials (RCTs) developed worldwide which have generated conflicting results.

The critical evaluation of clinical evidence on the safety and efficacy of autologous adult bone marrow-derived stem cells (BMSC) as a treatment for chronic ischaemic heart disease (IHD) and heart failure.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013, Issue 3), MEDLINE (from 1950), EMBASE (from 1974), CINAHL (from 1982) and the Transfusion Evidence Library (from 1980), together with ongoing trial databases, for relevant trials up to 31st March 2013.

Eligible studies included RCTs comparing autologous adult stem/progenitor cells with no autologous stem/progenitor cells in participants with chronic IHD and heart failure. Co-interventions such as primary angioplasty, surgery or administration of stem cell mobilising agents, were included where administered to treatment and control arms equally.

Two review authors independently screened all references for eligibility, assessed trial quality and extracted data. We undertook a quantitative evaluation of data using fixed-effect meta-analyses. We evaluated heterogeneity using the I² statistic; we explored considerable heterogeneity (I² > 75%) using a random-effects model and subgroup analyses.

We include 23 RCTs involving 1255 participants in this review. Risk of bias was generally low, with the majority of studies reporting appropriate methods of randomisation and blinding, Autologous bone marrow stem cell treatment reduced the incidence of mortality (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.14 to 0.53, P = 0.0001, 8 studies, 494 participants, low quality evidence) and rehospitalisation due to heart failure (RR 0.26, 95% CI 0.07 to 0.94, P = 0.04, 2 studies, 198 participants, low quality evidence) in the long term (≥12 months). The treatment had no clear effect on mortality (RR 0.68, 95% CI 0.32 to 1.41, P = 0.30, 21 studies, 1138 participants, low quality evidence) or rehospitalisation due to heart failure (RR 0.36, 95% CI 0.12 to 1.06, P = 0.06, 4 studies, 236 participants, low quality evidence) in the short term (< 12 months), which is compatible with benefit, no difference or harm. The treatment was also associated with a reduction in left ventricular end systolic volume (LVESV) (mean difference (MD) -14.64 ml, 95% CI -20.88 ml to -8.39 ml, P < 0.00001, 3 studies, 153 participants, moderate quality evidence) and stroke volume index (MD 6.52, 95% CI 1.51 to 11.54, P = 0.01, 2 studies, 62 participants, moderate quality evidence), and an improvement in left ventricular ejection fraction (LVEF) (MD 2.62%, 95% CI 0.50% to 4.73%, P = 0.02, 6 studies, 254 participants, moderate quality evidence), all at long-term follow-up. Overall, we observed a reduction in functional class (New York Heart Association (NYHA) class) in favour of BMSC treatment during short-term follow-up (MD -0.63, 95% CI -1.08 to -0.19, P = 0.005, 11 studies, 486 participants, moderate quality evidence) and long-term follow-up (MD -0.91, 95% CI -1.38 to -0.44, P = 0.0002, 4 studies, 196 participants, moderate quality evidence), as well as a difference in Canadian Cardiovascular Society score in favour of BMSC (MD -0.81, 95% CI -1.55 to -0.07, P = 0.03, 8 studies, 379 participants, moderate quality evidence). Of 19 trials in which adverse events were reported, adverse events relating to the BMSC treatment or procedure occurred in only four individuals. No long-term adverse events were reported. Subgroup analyses conducted for outcomes such as LVEF and NYHA class revealed that (i) route of administration, (ii) baseline LVEF, (iii) cell type, and (iv) clinical condition are important factors that may influence treatment effect.

This systematic review and meta-analysis found moderate quality evidence that BMSC treatment improves LVEF. Unlike in trials where BMSC were administered following acute myocardial infarction (AMI), we found some evidence for a potential beneficial clinical effect in terms of mortality and performance status in the long term (after at least one year) in people who suffer from chronic IHD and heart failure, although the quality of evidence was low.

Ischemic cerebral infarction is a leading cause of death and disability, but the key inflammatory cytokines were not fully understood and no successful therapy has been established. We have used the methods of reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), western blot, and immunohistochemical staining to detect the dynamic changes of IL-23/IL-17 axis in brain infarction and BMSC treatment on the sixth day. BMSC transplantation could reduce the infarct size (P<0.05) and improve functional deficits (P<0.001) in brain infarction. The level of IL-23/IL-17 axis expression is higher (P<0.05) in pMCAO-operated group than that in sham operated group. BMSC treatment could reduce IL-23 expression (P<0.05) and attenuate IL-17 expression (P<0.01) both in serum and around infarct lesion. So we have drawn the conclusion that IL-23/IL-17 axis induces inflammation in the pathophysiological process of cerebral infarction. BMSC treatment plays therapeutic role by immunomodulating the expression of IL-23/IL-17 axis. These findings may help to understand the cytokines in cerebral infarction and open up a possible new way of immunological treatment.