Percutaneous cell delivery into the heart using hydrogels polymerizing in situ.
Percutaneous cell delivery into the heart using hydrogels polymerizing in situ.
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DOI：
10.3727/096368909788534915
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发表时间：
2009
影响因子：
3.3
通讯作者：
Vunjak-Novakovic G
中科院分区：
文献类型：
--
作者：
Martens TP;Godier AF;Parks JJ;Wan LQ;Koeckert MS;Eng GM;Hudson BI;Sherman W;Vunjak-Novakovic G
在美国，心脏病是导致死亡的主要原因。急性心肌梗死后，纤维性、非收缩性疤痕形成，每年在美国有超过50万患者导致充血性心力衰竭。肌肉再生和诱导新血管生长治疗心脏缺血性疾病具有重要的治疗意义。在慢性缺血性SLVD患者中使用骨骼肌母细胞或骨髓源性细胞的早期研究报告了左心室射血功能（LVEF）和临床状态的改善，没有明显的安全性问题。然而，细胞转移治疗心血管疾病的有效性尚未确定，部分原因是缺乏对细胞保留、存活和递送后功能的控制。我们研究了使用可原位聚合的生物相容性水凝胶作为细胞递送载体，以改善细胞在递送到缺血心肌后的保留、存活和功能。这项研究是使用人骨髓间充质干细胞和纤维蛋白胶进行的，但该方法适用于任何人类干细胞（成人或胚胎）和各种水凝胶。我们首先评估了几种市售的经皮导管用于输送粘性细胞/水凝胶悬浮液的效用。接下来，我们表征了纤维蛋白胶溶液的聚合动力学，以确定与导管输送相容的浓度范围。然后，我们在裸鼠心肌梗死模型中证明了该制剂的体内有效性及其增加细胞保留和存活的能力。
Heart disease is the leading cause of death in the US. Following an acute myocardial infarction, a fibrous, noncontractile scar develops, and results in congestive heart failure in more than 500,000 patients in the US each year. Muscle regeneration and the induction of new vascular growth to treat ischemic disorders of the heart can have significant therapeutic implications. Early studies in patients with chronic ischemic SLVD using skeletal myoblasts or bone marrow-derived cells report improvement in left ventricular ejection function (LVEF) and clinical status, without notable safety issues. Nonetheless, the efficacy of cell transfer for cardiovascular disease is not established, in part due to a lack of control over cell retention, survival, and function following delivery. We studied the use of biocompatible hydrogels polymerizable in situ as a cell delivery vehicle, to improve cell retention, survival, and function following delivery into the ischemic myocardium. The study was conducted using human bone marrow-derived mesenchymal stem cells and fibrin glue, but the methods are applicable to any human stem cells (adult or embryonic) and a wide range of hydrogels. We first evaluated the utility of several commercially available percutaneous catheters for delivery of viscous cell/hydrogel suspensions. Next we characterized the polymerization kinetics of fibrin glue solutions to define the ranges of concentrations compatible with catheter delivery. We then demonstrate the in vivo effectiveness of this preparation and its ability to increase cell retention and survival in a nude rat model of myocardial infarction.
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DOI：
10.1073/pnas.0407817101
发表时间：
2004-12-28
影响因子：
11.1
作者：
Radisic, M;Park, H;Vunjak-Novakovic, G
通讯作者：
Vunjak-Novakovic, G
影响因子：
5
作者：
Penn, Emerson C.;Silva, Guilherme V.;Willerson, James T.
通讯作者：
Willerson, James T.
影响因子：
37.8
作者：
Hou, DM;Youssef, EAS;March, KL
通讯作者：
March, KL
影响因子：
3.3
作者：
Hayashi, M;Li, TS;Hamano, K
通讯作者：
Hamano, K
影响因子：
14
作者：
Ferreira, Lino S.;Gerecht, Sharon;Langer, Robert
通讯作者：
Langer, Robert