心臓のエンジニアリングの核心に迫る(Getting to the heart of engineering a heart)

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ヒト幹細胞由来の臓器構成ブロックを用いてバイオプリントした心臓組織の機能層に、収縮力をプログラムできる新たな組織工学の可能性を発見 New tissue engineering capabilities enable researchers to program contractility in functional layers of heart tissue bioprinted with human stem cell-derived organ building blocks

2022-06-10 ハーバード大学


To create layers of aligned contractile human heart muscle tissue, the team first developed a platform with which they could simultaneously generate 1050 individual contractile Organ Building Blocks (OBBs) between two micropillars, using human induced Pluripotent Stem Cells (hiPSCs), human fibroblast cells and essential extracellular matrix molecules (ECMs). The OBBs were then lifted off the micropillars and used as a feedstock to fabricate a dense bioink (lower panel). In a second alignment step the mechanical shear forces generated at the print head during the printing process act on the OBBs while they are being extruded to give them directionality in printed cardiac tissue sheets. Credit: Wyss Institute at Harvard University

新しい心臓工学技術を開発し、心臓の収縮要素の配置を模倣することを可能にしました。ヒト人工多能性幹細胞(hiPSCs-CM)由来の心筋細胞からなる収縮性器官構築ブロック(OBB)が密に詰まったバイオインクを用いて、複雑で変化に富んだ配列の心筋組織シートを印刷することができたのです。このシートは、実際のヒトの心筋層と同様の組織と機能を有しています。この研究成果は、『Advanced Materials』誌に掲載された。将来的には、この進歩により、より生理的な収縮特性をもつ厚い多層構造のヒトの筋肉組織を開発できるようになる可能性があります。

<関連情報>

異方性器官ブロックのバイオプリントによる人工心筋組織における細胞配列のプログラミング Programming Cellular Alignment in Engineered Cardiac Tissue via Bioprinting Anisotropic Organ Building Blocks

John H. Ahrens,Sebastien G. M. Uzel,Mark Skylar-Scott,Mariana M. Mata,Aric Lu,Katharina T. Kroll,Jennifer A. Lewis
Advanced Materials  Published: 21 April 2022
DOI:https://doi.org/10.1002/adma.202200217

Abstract

The ability to replicate the 3D myocardial architecture found in human hearts is a grand challenge. Here, the fabrication of aligned cardiac tissues via bioprinting anisotropic organ building blocks (aOBBs) composed of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is reported. A bioink composed of contractile cardiac aOBBs is first generated and aligned cardiac tissue sheets with linear, spiral, and chevron features are printed. Next, aligned cardiac macrofilaments are printed, whose contractile force and conduction velocity increase over time and exceed the performance of spheroid-based cardiac tissues. Finally, the ability to spatially control the magnitude and direction of contractile force by printing cardiac sheets with different aOBB alignment is highlighted. This research opens new avenues to generating functional cardiac tissue with high cell density and complex cellular alignment.

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