Stem cell news: Lancet: 自体心肌干细胞减少心肌缺血后瘢痕形成并促进心肌再生

kittybruce

Cedars-Sinai Heart Institute的I期临床试验，纳入自体心肌干细胞治疗组有17名患者，用经颈静脉导管获取的“半粒葡萄干”大小的心肌组织，培养出2500万自体细胞，打入心肌周围动脉。半年后左室疤痕从24%降至16%，一年后降至12%，并有新生心肌形成。
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' H# U; G, A, hThe Lancet, Early Online Publication, 14 February 2012
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Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial
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+ t8 o' g5 z. s& T" N  ~Raj R Makkar MD a, Rachel R Smith PhD a, Ke Cheng PhD a, Konstantinos Malliaras MD a, Louise EJ Thomson MD a, Prof Daniel Berman MD a, Lawrence SC Czer MD a, Linda Marbán PhD a, Adam Mendizabal MS b, Peter V Johnston MD c, Stuart D Russell MD c, Karl H Schuleri MD c, Albert C Lardo PhD c, Prof Gary Gerstenblith MD c, Prof Eduardo Marbán MD a Corresponding AuthorEmail Address% w8 ?0 u) v. V, `
Summary
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9 |( b% B5 Z0 Y( Z1 `Cardiosphere-derived cells (CDCs) reduce scarring after myocardial infarction, increase viable myocardium, and boost cardiac function in preclinical models. We aimed to assess safety of such an approach in patients with left ventricular dysfunction after myocardial infarction.: c# ^4 m) }; F2 ]/ [6 H
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In the prospective, randomised CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial, we enrolled patients 2—4 weeks after myocardial infarction (with left ventricular ejection fraction of 25—45%) at two medical centres in the USA. An independent data coordinating centre randomly allocated patients in a 2:1 ratio to receive CDCs or standard care. For patients assigned to receive CDCs, autologous cells grown from endomyocardial biopsy specimens were infused into the infarct-related artery 1·5—3 months after myocardial infarction. The primary endpoint was proportion of patients at 6 months who died due to ventricular tachycardia, ventricular fibrillation, or sudden unexpected death, or had myocardial infarction after cell infusion, new cardiac tumour formation on MRI, or a major adverse cardiac event (MACE; composite of death and hospital admission for heart failure or non-fatal recurrent myocardial infarction). We also assessed preliminary efficacy endpoints on MRI by 6 months. Data analysers were masked to group assignment. This study is registered with ClinicalTrials.gov, NCT00893360.  k3 W- k2 u! c7 |
Findings
/ i7 k3 d$ O& M5 J1 n. r4 hBetween May 5, 2009, and Dec 16, 2010, we randomly allocated 31 eligible participants of whom 25 were included in a per-protocol analysis (17 to CDC group and eight to standard of care). Mean baseline left ventricular ejection fraction (LVEF) was 39% (SD 12) and scar occupied 24% (10) of left ventricular mass. Biopsy samples yielded prescribed cell doses within 36 days (SD 6). No complications were reported within 24 h of CDC infusion. By 6 months, no patients had died, developed cardiac tumours, or MACE in either group. Four patients (24%) in the CDC group had serious adverse events compared with one control (13%; p=1·00). Compared with controls at 6 months, MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001), increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months.
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$ ?% C" G4 u5 t* Q' X# s. `5 IWe show intracoronary infusion of autologous CDCs after myocardial infarction is safe, warranting the expansion of such therapy to phase 2 study. The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes.
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# |+ J$ O6 ~( X1 e  AUS National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center.$ b/ l" }, L/ B
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4 f  N" x* j. b* n( @2 Y14 February 2012 Last updated at 00:52 2 j; W2 s4 C! |5 P1 t4 J
Stem cells used to 'heal' heart attack scars, z3 P( j* y- `  Z4 n' E
By James Gallagher
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Damage caused by a heart attack has been healed using stem cells gathered from the patient's own heart, according to doctors in the US.
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* i; r1 f  i3 ]  P; uThe amount of scar tissue was halved in the small safety trial reported in the Lancet medical journal.
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The authors said there was also an "unprecedented" increase in new heart muscle.
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" B& }4 d1 i6 S- fThe British Heart Foundation said it was "early days", but could "be great news for heart attack patients".
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- r" d  e. N0 s2 A4 T* H. ~. gA heart attack happens when the organ is starved of oxygen, such as a clot blocking the flow of blood to the heart.& {, I. f8 @7 E" Z, j! S

& E6 n$ q9 M4 r9 u9 y& ]/ t6 nAs the heart heals, the dead muscle is replaced with scar tissue, but because this does not beat like heart muscle the ability to pump blood around the body is reduced.
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Doctors around the world are looking at ways of "regenerating" the heart to replace the scar tissue with beating muscle. Stem cells, which can transform into any other type of specialised cell, figure prominently in their plans.- d8 E3 H  M; r% J  C# }8 S
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This trial, at the Cedars-Sinai Heart Institute, was designed to test the safety of using stem cells taken from a heart attack patient's own heart.
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. `" r1 c8 |# K6 B/ p+ Q  e' C# hWithin a month of a heart attack, a tube was inserted into a vein in the patient's neck and was pushed down towards the heart. A sample of heart tissue, about "half the size of a raisin", was taken.  R' M% G9 Z) }$ {1 W

# o9 L. O8 D  ?) N+ |This was taken to the laboratory where the stem cells were isolated and grown. Up to 25 million of these stem cells were then put into the arteries surrounding the heart.5 `1 }3 M, y' t

9 }( `! V3 Q) y3 b9 y: W- ^Twenty five patients took part in the trial. Before the treatment, scar tissue accounted for an average of 24% of their left ventricle, a major chamber of the heart. It went down to 16% after six months and 12% after a year.
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Healthy heart muscle appeared to take its place. The study said the cells, "have an unprecedented ability to reduce scar and simultaneously stimulate the regrowth of healthy [heart] tissue".% ]: f2 s# L0 |" @8 B+ @  V6 n
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One of the researchers Dr Eduardo Marban said: "While the primary goal of our study was to verify safety, we also looked for evidence that the treatment might dissolve scar and regrow lost heart muscle." Q( |- d4 M# Z3 U; ^* R
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"This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it.
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"The effects are substantial, and surprisingly larger in humans than they were in animal tests."' w; o& a% b% f" E6 f
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However, there was no increase in a significant measure of the heart's ability to pump - the left ventricle ejection fraction: the percentage of blood pumped out of the left ventricle.1 n" Z& G3 K+ |; O- R
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Prof Anthony Mathur, who is co-ordinating a stem cell trial involving 3,000 heart attack patients, said that even if the study found an increase in ejection fraction then it would be the source of much debate.
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: q' \- c# a- I# ?He argued that as it was a proof-of-concept study, with a small group of patients, "proving it is safe and feasible is all you can ask".2 G# Q' m% `# Q  c( y9 b5 ?# V
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"The findings would be very interesting, but obviously they need further clarification and evidence," he added.
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% _# ]2 R5 Y9 \& p* T" E. hProf Jeremy Pearson, associate medical director at the British Heart Foundation, said: "It's the first time these scientists' potentially exciting work has been carried out in humans, and the results are very encouraging.2 h8 N* h! ]5 P* F3 G3 Y9 N0 `
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"These cells have been proven to form heart muscle in a petri dish but now they seem to be doing the same thing when injected back into the heart as part of an apparently safe procedure.7 m" a3 @, T: s( R1 T

/ o# a  x! e" w, s7 {: T: B, c"It's early days, and this research will certainly need following up, but it could be great news for heart attack patients who face the debilitating symptoms of heart failure."
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LA Times
6 [2 X. q5 V1 M1 hStudy: Cardiac stem cells can reverse heart attack damage, w9 ~2 C% s  X& r$ N; F* h2 v

- ]# {, `. t7 b) k7 bBy Eryn Brown, Los Angeles Times / for the Booster Shots blog6 h4 l/ y( ]" D7 ~9 ~+ T! ^
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February 13, 2012, 5:45 p.m.% B2 L0 y% H: G+ t3 [- H4 Z: y/ j
Researchers have used cardiac stem cells to regenerate heart muscle in patients who have suffered heart attacks, also known as myocardial infarction.
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. M2 h5 Z7 N0 r4 x. ]The small preliminary study, which was conducted by the Cedars-Sinai Heart Institute in Los Angeles, involved 25 patients who had suffered heart attacks in the previous one and a half to three months.
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Seventeen of the study subjects received infusions of stem cells cultured from a raisin-sized chunk of their own heart tissue, which had been removed via catheter. The eight others received standard care.
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During a heart attack, heart tissue is damaged, leaving a scar.  On average, scars in patients who had the stem cell infusions dropped in size from 24% to 12% of the heart, said Dr. Eduardo Marbán, director of the Cedars-Sinai Heart Institute and lead researcher on the study, which was published online Monday in the journal The Lancet.  (The journal has provided an abstract of the study; subscription is required for the full text.)
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  w+ @* L# E  O/ i" y+ K7 [In an email, Marbán said he believed that the stem cells repaired the damaged heart muscle "indirectly, by stimulating the heart's endogenous capacity to regrow [which normally lies dormant]." He said that the most surprising aspect of the research team's finding was that the heart was able to regrow healthy tissue. Conventional wisdom holds that cardiac scarring is permanent.
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7 ^# a, J2 T/ ^2 ~0 `( o: m) y2 eA follow-up study involving about 200 patients is planned for later this year, Marbán added.
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