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人造心脏组织补丁以剂量依赖的方式重新肌肉化受伤的心脏

Eva Querdel^1,2, Marina Reinsch^1,2, Liesa Castro^3,2,4

¹Department of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.

|March 2, 2021

概括

人工工程心脏组织 (EHT) 贴片对心力衰竭治疗具有前景,以剂量依赖的方式改善功能. 在猪身上成功移植了人体尺寸的贴片,为临床应用铺平了道路.

科学领域:

复原医学
心血管生物学
生物技术

背景情况:

人工心脏组织移植是一种潜在的心力衰竭再生疗法,在临床前研究中被证明是有效的.
临床转换需要根据良好的制造实践 (GMP) 提高EHT生产规模,并确定最佳治疗剂量.
目前面临的挑战包括适应大型符合GMP的EHT产生的协议,并评估相关模型的有效性.

研究的目的:

在心力衰竭患者中开发和评估人造心脏组织 (EHT) 补丁.
适应EHT生成协议以符合良好制造实践 (GMP) 和扩大规模.
在临床前模型中评估EHT移植的疗效和安全性,并评估人类尺度上的贴片可行性.

主要方法:

从人类GMP级诱导多能干细胞 (hiPSCs) 中分化的心肌细胞.
使用符合GMP的材料进行hiPSC扩张,心肌细胞分化和EHT生成的调整方案.
为几内亚猪和猪模型创建了不同尺寸的网状结构的EHT贴片,修改了移植的几何形状.

主要成果:

产生的EHT贴片 (1.5x2.5厘米的试验猪, 5x7厘米的猪) 具有成熟的心肌细胞,表现出人心室组织特征.
将EHT贴片移植到冷受伤的海豚心脏中,观察剂量依赖的肌肉化 (0-12%的痕覆盖率).
高剂量的EHT贴片显著改善左心室功能 (+8%绝对, +24%相对) 并显示心肌细胞增殖;人类尺寸的贴片在猪中成功移植.

结论:

在几内亚猪中,EHT贴片移植使受伤的心脏部分肌肉化,并以剂量依赖的方式改善左心室功能.
在猪体内成功移植了人体尺寸的EHT贴片,证明了临床可行性.
这些发现支持EHT移植作为心力衰竭的可行的再生策略.

关键词:

细胞移植复原医学干细胞

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