2012年9月26日 訊 /生物谷BIOON/ --磁性納米顆粒能夠正向地影響移植的干細(xì)胞的靶向運(yùn)送。兩項(xiàng)刊登于當(dāng)前一期Cell Transplantation期刊上的研究證實(shí)利用這種納米顆粒如何提供更好的細(xì)胞停留能力。
在第一項(xiàng)研究中，來(lái)自加拿大英屬哥倫比亞大學(xué)的研究人員磁性干細(xì)胞靶向技術(shù)來(lái)改善間充質(zhì)干細(xì)胞(mensenchymal stem cell, MSC)運(yùn)送和傳輸?shù)綔y(cè)試大鼠的視網(wǎng)膜之中,。而在第二項(xiàng)研究中，來(lái)自美國(guó)洛杉磯市希達(dá)-西奈心臟研究所(Cedars-Sinai Heart Institute)的研究人員注射磁性加強(qiáng)的心臟干細(xì)胞到遭受缺血再灌注損傷的模式大鼠體內(nèi)以便引導(dǎo)這些細(xì)胞到達(dá)靶位置從而增加細(xì)胞停留和治療效果。
在第一項(xiàng)研究中,，英屬哥倫比亞大學(xué)視網(wǎng)膜黃斑退化中心研究員Kevin Gregory-Evans博士說(shuō)，視網(wǎng)膜退化---為黃斑退化何其他眼睛疾病的病因---能夠解釋發(fā)達(dá)世界中的大多數(shù)失明病例,。在此之前,，將間充質(zhì)干細(xì)胞移植到受損視網(wǎng)膜之中只能取得有限的成功，這是因?yàn)檫_(dá)到視網(wǎng)膜的細(xì)胞非常少,，而且是隨機(jī)分布的,。
為了尋求改善干細(xì)胞移植到視網(wǎng)膜的方法,，研究人員利用超順磁性氧化鐵納米顆粒(superparamagnetic iron oxide nanoparticle, SPION)讓大鼠間充質(zhì)干細(xì)胞磁化。通過(guò)一塊外部放置的磁鐵,，他們引導(dǎo)SPION強(qiáng)化的干細(xì)胞到測(cè)試大鼠的周邊視網(wǎng)膜(peripheral retina)之中
Gregory-Evans解釋道,，“我們的結(jié)果表明大量血源性磁性間充質(zhì)干細(xì)胞能夠靶向特定的視網(wǎng)膜位置并導(dǎo)致靶組織發(fā)生治療上有用的生物化學(xué)變化。這種方法在治療外視網(wǎng)膜局部組織疾病(比如老年性黃斑退化癥)中應(yīng)當(dāng)是最佳的,。”
在第二項(xiàng)研究中,，希達(dá)-西奈心臟研究所研究人員說(shuō)，心臟干細(xì)胞代表著一種大有希望的再生受損心肌的候選方法,。然而,，由于周期性心臟收縮，靜脈沖洗(venous washout)導(dǎo)致極低數(shù)量的干細(xì)胞停留,，從而破壞干細(xì)胞移植的潛在有益影響,。
論文通信作者Eduardo Marban博士說(shuō)，“因?yàn)楣跔顒?dòng)脈內(nèi)干細(xì)胞移植受到低數(shù)量干細(xì)胞停留的限制,，所以我們尋求通過(guò)磁性靶向作用來(lái)改善干細(xì)胞停留,。”
在簡(jiǎn)短的主動(dòng)脈鉗夾夾緊期間，研究人員將用鐵微球(iron microsphere)標(biāo)記的心臟干細(xì)胞注射到同系大鼠的左心室腔,。在24小時(shí)之后,，他們發(fā)現(xiàn)在注射期間和注射額之后放置一塊磁鐵到心臟之上，干細(xì)胞停留能力能夠提高了5倍多,。
Marban說(shuō),，“干細(xì)胞療法的成功依賴于它們能夠有效地運(yùn)送到預(yù)定的區(qū)域。在心臟中,，心臟收縮在細(xì)胞運(yùn)送期間和在細(xì)胞運(yùn)送之后導(dǎo)致細(xì)胞數(shù)量顯著性下降,。我們發(fā)現(xiàn)磁吸引力能夠讓鐵標(biāo)記的治療試劑集中于靶區(qū)域內(nèi)，這樣我們成功地利用磁性來(lái)對(duì)抗靜脈沖洗和改善收縮性心臟中的細(xì)胞停留能力,。”(生物谷：Bioon.com)
doi: 10.3727/096368911X627435
PMC:
PMID:
Focused Magnetic Stem Cell Targeting to the Retina Using Superparamagnetic Iron Oxide Nanoparticles
Yanai, Anat1; Häfeli, Urs O.2; Metcalfe, Andrew L.1; Soema, Peter2; Addo, Lois1; Gregory-Evans, Cheryl Y.1; Po, Kelvin1; Shan, Xianghong1; Moritz, Orson L.1; Gregory-Evans, Kevin
Developing new ways of delivering cells to diseased tissue will be a key factor in translating cell therapeutics research into clinical use. Magnetically targeting cells enables delivery of significant numbers of cells to key areas of specific organs. To demonstrate feasibility in neurological tissue, we targeted cells magnetically to the upper hemisphere of the rodent retina. Rat mesenchymal stem cells (MSCs) were magnetized using superparamagnetic iron oxide nanoparticles (SPIONs). In vitro studies suggested that magnetization with fluidMAG-D was well tolerated, that cells remained viable, and they retained their differentiation capabilities. FluidMAG-D-labeled MSCs were injected intravitreally or via the tail vein of the S334ter-4 transgenic rat model of retinal degeneration with or without placing a gold-plated neodymium disc magnet within the orbit, but outside the eye. Retinal flatmount and cryosection imaging demonstrated that after intravitreal injection cells localized to the inner retina in a tightly confined area corresponding to the position of the orbital magnet. After intravenous injection, similar retinal localization was achieved and remarkably was associated with a tenfold increase in magnetic MSC delivery to the retina. Cryosections demonstrated that cells had migrated into both the inner and outer retina. Magnetic MSC treatment with orbital magnet also resulted in significantly higher retinal concentrations of anti-inflammatory molecules interleukin-10 and hepatocyte growth factor. This suggested that intravenous MSC therapy also resulted in significant therapeutic benefit in the dystrophic retina. With minimal risk of collateral damage, these results suggest that magnetic cell delivery is the best approach for controlled delivery of cells to the outer retina-the focus for disease in age-related macular degeneration and retinitis pigmentosa.
doi: 10.3727/096368911X627381
PMC:
PMID:
Magnetic Enhancement of Cell Retention, Engraftment, and Functional Benefit After Intracoronary Delivery of Cardiac-Derived Stem Cells in a Rat Model of Ischemia/Reperfusion
Cheng, Ke; Malliaras, Konstantinos; Li, Tao-Sheng; Sun, Baiming; Houde, Christiane; Galang, Giselle; Smith, Jeremy; Matsushita, Noriko; Marbán, Eduardo
The efficiency of stem cell transplantation is limited by low cell retention. Intracoronary (IC) delivery is convenient and widely used but exhibits particularly low cell retention rates. We sought to improve IC cell retention by magnetic targeting. Rat cardiosphere-derived cells labeled with iron microspheres were injected into the left ventricular cavity of syngeneic rats during brief aortic clamping. Placement of a 1.3 Tesla magnet ∼1 cm above the heart during and after cell injection enhanced cell retention at 24 h by 5.2-6.4-fold when 1, 3, or 5 × 105 cells were infused, without elevation of serum troponin I (sTnI) levels. Higher cell doses (1 or 2 × 106 cells) did raise sTnI levels, due to microvascular obstruction; in this range, magnetic enhancement did not improve cell retention. To assess efficacy, 5 × 105 iron-labeled, GFP-expressing cells were infused into rat hearts after 45 min ischemia/20 min reperfusion of the left anterior coronary artery, with and without a superimposed magnet. By quantitative PCR and optical imaging, magnetic targeting increased cardiac retention of transplanted cells at 24 h, and decreased migration into the lungs. The enhanced cell engraftment persisted for at least 3 weeks, at which time left ventricular remodeling was attenuated, and therapeutic benefit (ejection fraction) was higher, in the magnetic targeting group. Histology revealed more GFP+ cardiomyocytes, Ki67+ cardiomyocytes and GFP−/ckit+ cells, and fewer TUNEL+ cells, in hearts from the magnetic targeting group. In a rat model of ischemia/reperfusion injury, magnetically enhanced intracoronary cell delivery is safe and improves cell therapy outcomes.
