美国波士顿大学Darrell N. Kotton研究组报道，他们将多能干细胞（PSC）来源的肺上皮细胞持久植入免疫功能正常的小鼠肺泡中。相关论文于2023年8月24日发表在《细胞-干细胞》杂志上。

研究人员成功将小鼠PSC分化为具有自我更新的肺上皮祖细胞，并能够移植到免疫功能正常的同系小鼠受损远端肺上皮中。移植后，这些祖细胞在远端肺中成熟，并具有肺泡2型（AT2）和1型（AT1）细胞分子表型。在体内存在数月后，供体来源的细胞保留其成熟的表型，利用单细胞RNA测序（scRNA-seq）、组织学分析和功能评估其特征，表明移植细胞具有持续的增殖和分化能力。

这些结果表明，远端肺的兼性祖细胞和分化的上皮细胞区室与PSC来源的细胞维持了持久重建，从而建立了一种新的肺细胞治疗模型，可用于更好地了解细胞移植的机制和效用。

据了解，用PSC衍生细胞实现远端肺上皮重建将是治疗肺泡损伤引起疾病的潜在治疗方法。

附：英文原文

Title: Durable alveolar engraftment of PSC-derived lung epithelial cells into immunocompetent mice

Author: Michael J. Herriges, Maria Yampolskaya, Bibek R. Thapa, Jonathan Lindstrom-Vautrin, Feiya Wang, Jessie Huang, Cheng-Lun Na, Liang Ma, McKenna M. Montminy, Pushpinder Bawa, Carlos Villacorta-Martin, Pankaj Mehta, Darrell N. Kotton

Issue&Volume: 2023-08-24

Abstract: Durable reconstitution of the distal lung epithelium with pluripotent stem cell (PSC) derivatives, if realized, would represent a promising therapy for diseases that result from alveolar damage. Here, we differentiate murine PSCs into self-renewing lung epithelial progenitors able to engraft into the injured distal lung epithelium of immunocompetent, syngeneic mouse recipients. After transplantation, these progenitors mature in the distal lung, assuming the molecular phenotypes of alveolar type 2 (AT2) and type 1 (AT1) cells. After months in vivo, donor-derived cells retain their mature phenotypes, as characterized by single-cell RNA sequencing (scRNA-seq), histologic profiling, and functional assessment that demonstrates continued capacity of the engrafted cells to proliferate and differentiate. These results indicate durable reconstitution of the distal lung’s facultative progenitor and differentiated epithelial cell compartments with PSC-derived cells, thus establishing a novel model for pulmonary cell therapy that can be utilized to better understand the mechanisms and utility of engraftment.

DOI: 10.1016/j.stem.2023.07.016

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00283-7