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具有保留且可比功能的人原代胰岛和诱导多能干细胞衍生胰岛的生物打印。

Bioprinting of human primary and iPSC-derived islets with retained and comparable functionality.

作者信息

Poklar Miranda, K Ravikumar, Wiegand Connor, Mizerak Ben, Wang Ruiqi, Florentino Rodrigo M, Liu Zhenghao, Soto-Gutierrez Alejandro, Kumta Prashant N, Banerjee Ipsita

机构信息

Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15213, United States of America.

Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15213, United States of America.

出版信息

Biofabrication. 2025 Jul 15;17(3). doi: 10.1088/1758-5090/ade933.

Abstract

Currently, type 1 diabetes (T1D) can be treated through implantation of allogenic islets, which replenish the beta cell population, however this method requires an extensive post-implantation immunosuppressant regimen. Personalized cellular therapy can address this through implantation of an autologous cell population, induced pluripotent stem cells (iPSCs). Cellular therapy, however, requires an encapsulation device for implantation, and so to achieve this uniformly with cells in a clinical setting, bioprinting is a useful option. Bioprinting is dependent on having a bioink that is printable, retains structural fidelity after printing, and is supportive of cell type and function. While bioprinting of pancreatic islets has been demonstrated previously, success in maintaining islet function post-printing has been varied. The objective of this study is to investigate the feasibility of printing functional islets by determining the appropriate combination of bioink, printing parameters, and cell configuration. Here, we detail the successful bioprinting of both primary human islets and iPSC-derived islets embedded in an alginate/methylcellulose bioink, with functionality sustained within the construct for both cell lineages. Sc-RNAseq analysis also revealed that printing did not adversely affect the genetic expression and metabolic functionality of the iPSC-derived islets. Importantly, the iPSC-derived islets displayed comparable functionality to the primary islets, indicating the potential to act as a cell source alternative for T1D implantation.

摘要

目前,1型糖尿病(T1D)可通过植入同种异体胰岛来治疗,这些胰岛可补充β细胞群,然而这种方法需要广泛的植入后免疫抑制方案。个性化细胞疗法可通过植入自体细胞群,即诱导多能干细胞(iPSC)来解决这一问题。然而,细胞疗法需要一种用于植入的封装装置,因此为了在临床环境中与细胞均匀地实现这一点,生物打印是一个有用的选择。生物打印依赖于一种可打印的生物墨水,这种墨水在打印后能保持结构保真度,并且支持细胞类型和功能。虽然之前已经证明了胰腺胰岛的生物打印,但打印后维持胰岛功能的成功率各不相同。本研究的目的是通过确定生物墨水、打印参数和细胞配置的适当组合,来研究打印功能性胰岛的可行性。在这里,我们详细介绍了成功地将原代人胰岛和iPSC衍生的胰岛嵌入藻酸盐/甲基纤维素生物墨水中进行生物打印,两种细胞谱系的构建物中均维持了功能。单细胞RNA测序分析还表明,打印不会对iPSC衍生的胰岛的基因表达和代谢功能产生不利影响。重要的是,iPSC衍生的胰岛显示出与原代胰岛相当的功能,表明其有潜力作为T1D植入的细胞来源替代品。

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