來(lái)自Cedars-Sinai心臟研究所的臨床試驗(yàn)結(jié)果表明,，給病人注入他們自己的心臟來(lái)源細(xì)胞有助于受損心臟再生出健康心肌。
心臟病發(fā)作會(huì)在心肌留下疤痕,。對(duì)接受實(shí)驗(yàn)性干細(xì)胞治療的病人而言,，這種疤痕大小顯著地減少，而且健康心肌發(fā)生相當(dāng)大的增加,。
在接受干細(xì)胞治療一年后,，接受細(xì)胞治療的病人心臟中疤痕大小減少24%到12%不等(平均下降率約50%)。而沒(méi)接受干細(xì)胞治療的對(duì)照組病人心臟中疤痕大小沒(méi)有減小,。該研究的最初目標(biāo)是證實(shí)其安全性,，也想尋找關(guān)于這種治療方法可能溶解疤痕與再生受損心肌的證據(jù)。盡管心臟病病人細(xì)胞治療試驗(yàn)已有十年時(shí)間,，但是之前一直沒(méi)有取得這么好的結(jié)果,。過(guò)去，我們能做的所有事情就是通過(guò)迅速打開(kāi)被阻塞的動(dòng)脈來(lái)最小化心臟損傷?，F(xiàn)在,，此研究表明存在一種再生治療法，這種療法確實(shí)可能逆轉(zhuǎn)心臟病發(fā)作引起的損傷,。
名為CADUCEUS(CArdiosphere-Derived aUtologous stem CElls to Reverse ventricUlar dySfunction)的臨床試驗(yàn)是FDA批準(zhǔn)并由美國(guó)國(guó)家心臟,、肺和血液研究所支持的I期研究的一部分。在2009年,，作為此項(xiàng)研究的最初部分,，Marbán和他的研究團(tuán)隊(duì)世界上第一次實(shí)現(xiàn)用病人自己的心臟組織來(lái)培養(yǎng)特殊的心臟干細(xì)胞。然后,，這種干細(xì)胞被注射回病人心臟中來(lái)努力修補(bǔ)心臟病發(fā)作導(dǎo)致的心臟受損和再生出健康心肌,。
與此項(xiàng)研究相關(guān)的培養(yǎng)心臟來(lái)源干細(xì)胞的過(guò)程早期是由Marbán開(kāi)發(fā)的，當(dāng)時(shí)他是約翰·霍普金斯大學(xué)的教職人員,。約翰·霍普金斯大學(xué)已申請(qǐng)了這種過(guò)程的專(zhuān)利,，并已許可給一家Marbán博士有財(cái)務(wù)利益的公司。那家公司沒(méi)有提供資金用于支持這項(xiàng)臨床研究,。所有資金來(lái)源于美國(guó)國(guó)家衛(wèi)生研究院和Cedars-Sinai醫(yī)學(xué)中心,。（生物谷bioon.com）
doi:10.1016/S0140-6736(12)60195-0
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Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial
Raj R Makkar, Rachel R Smith , Ke Cheng, Konstantinos Malliaras , Louise EJ Thomson, Daniel Berman , Lawrence SC Czer, Linda Marbán, Adam Mendizabal , Peter V Johnston, Stuart D Russell, Karl H Schuleri , Albert C Lardo , Gary Gerstenblith , Eduardo Marbán
ABSTRACT Background: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. Methods: 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. Findings: Between 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. Interpretation：We 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. Funding: US National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center.
