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激光生物打印人类诱导多能干细胞——打印和生物材料对细胞存活、多能性和分化的影响。

Laser bioprinting of human induced pluripotent stem cells-the effect of printing and biomaterials on cell survival, pluripotency, and differentiation.

机构信息

REBIRTH-Cluster of Excellence, Hannover Medical School, D-30625, Hannover, Germany. Laser Zentrum Hannover e.V., Nanotechnology Department, D-30419, Hannover, Germany. NIFE-Lower Saxony Centre for Biomedical Engineering, Implant Research and Development, D-30625, Hannover, Germany.

出版信息

Biofabrication. 2018 Apr 25;10(3):035005. doi: 10.1088/1758-5090/aab981.

DOI:10.1088/1758-5090/aab981
PMID:29578448
Abstract

Research on human induced pluripotent stem cells (hiPSCs) is one of the fastest growing fields in biomedicine. Generated from patient's own somatic cells, hiPSCs can be differentiated towards all functional cell types and returned to the patient without immunological concerns. 3D printing of hiPSCs could enable the generation of functional organs for replacement therapies or realization of organ-on-chip systems for individualized medicine. Printing of living cells was demonstrated with immortalized cell lines, primary cells, and adult stem cells with different printing technologies and biomaterials. However, hiPSCs are more sensitive to handling procedures, in particular, when dissociated into single cells. Both pluripotency and directed differentiation are influenced by numerous environmental factors including culture media, biomaterials, and cell density. Notably, existing literature on the effect of applied biomaterials on pluripotency is rather ambiguous. In this study, laser bioprinting of undifferentiated hiPSCs in combination with different biomaterials was performed and the impact on cells' behavior, pluripotency, and differentiation was investigated. Our findings suggest that hiPSCs are indeed more sensitive to the applied biomaterials, but not to laser printing itself. With appropriate biomaterials, such as the hyaluronic acid based solutions applied in this study, hiPSCs can be successfully laser printed without losing their pluripotency.

摘要

人诱导多能干细胞(hiPSCs)的研究是生物医学中发展最快的领域之一。hiPSCs 可以从患者自身的体细胞中产生,并且可以分化为所有功能性细胞类型,然后再回输给患者,而不会引起免疫问题。hiPSCs 的 3D 打印可以实现功能性器官的生成,用于替代疗法,或者实现用于个体化医疗的器官芯片系统。使用不同的打印技术和生物材料,已经证明可以对永生化细胞系、原代细胞和成人干细胞进行活细胞打印。然而,hiPSCs 对处理程序更加敏感,特别是在将其分离成单细胞时。多能性和定向分化都受到许多环境因素的影响,包括培养基、生物材料和细胞密度。值得注意的是,关于应用生物材料对多能性的影响的现有文献相当模糊。在这项研究中,采用不同的生物材料对未分化的 hiPSCs 进行了激光生物打印,并研究了其对细胞行为、多能性和分化的影响。我们的研究结果表明,hiPSCs 确实对应用的生物材料更为敏感,但对激光打印本身并不敏感。通过使用合适的生物材料,如本研究中应用的基于透明质酸的溶液,可以成功地对 hiPSCs 进行激光打印,而不会丧失其多能性。

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