Zhang Wencheng, Wang Xicheng, Lanzoni Giacomo, Wauthier Eliane, Simpson Sean, Ezzell Jennifer Ashley, Allen Amanda, Suitt Carolyn, Krolik Jonah, Jhirad Alexander, Dominguez-Bendala Juan, Cardinale Vincenzo, Alvaro Domenico, Overi Diletta, Gaudio Eugenio, Sethupathy Praveen, Carpino Guido, Adin Christopher, Piedrahita Jorge A, Mathews Kyle, He Zhiying, Reid Lola McAdams
Department of Cell Biology and Physiology, University of North Carolina (UNC) School of Medicine, Chapel Hill, NC, 27599, USA.
Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University School of Medicine, 200123, Shanghai, China.
NPJ Regen Med. 2023 Aug 1;8(1):40. doi: 10.1038/s41536-023-00303-5.
A network of co-hepato/pancreatic stem/progenitors exists in pigs and humans in Brunner's Glands in the submucosa of the duodenum, in peribiliary glands (PBGs) of intrahepatic and extrahepatic biliary trees, and in pancreatic duct glands (PDGs) of intrapancreatic biliary trees, collectively supporting hepatic and pancreatic regeneration postnatally. The network is found in humans postnatally throughout life and, so far, has been demonstrated in pigs postnatally at least through to young adulthood. These stem/progenitors in vivo in pigs are in highest numbers in Brunner's Glands and in PDGs nearest the duodenum, and in humans are in Brunner's Glands and in PBGs in the hepato/pancreatic common duct, a duct missing postnatally in pigs. Elsewhere in PDGs in pigs and in all PDGs in humans are only committed unipotent or bipotent progenitors. Stem/progenitors have genetic signatures in liver/pancreas-related RNA-seq data based on correlation, hierarchical clustering, differential gene expression and principal component analyses (PCA). Gene expression includes representative traits of pluripotency genes (SOX2, OCT4), endodermal transcription factors (e.g. SOX9, SOX17, PDX1), other stem cell traits (e.g. NCAM, CD44, sodium iodide symporter or NIS), and proliferation biomarkers (Ki67). Hepato/pancreatic multipotentiality was demonstrated by the stem/progenitors' responses under distinct ex vivo conditions or in vivo when patch grafted as organoids onto the liver versus the pancreas. Therefore, pigs are logical hosts for translational/preclinical studies for cell therapies with these stem/progenitors for hepatic and pancreatic dysfunctions.
猪和人类的十二指肠黏膜下层的布伦纳腺、肝内和肝外胆管树的胆管周围腺体（PBGs）以及胰内胆管树的胰管腺体（PDGs）中存在共同的肝/胰腺干/祖细胞网络，共同支持出生后的肝脏和胰腺再生。该网络在人类出生后的一生中都存在，到目前为止，至少在猪出生后直至成年早期都已得到证实。猪体内的这些干/祖细胞在布伦纳腺和最靠近十二指肠的PDGs中数量最多，而在人类中则存在于布伦纳腺以及肝/胰共同导管中的PBGs中，猪出生后该导管缺失。在猪的PDGs其他部位以及人类所有的PDGs中仅存在定向的单能或双能祖细胞。基于相关性、层次聚类、差异基因表达和主成分分析（PCA），干/祖细胞在肝脏/胰腺相关的RNA测序数据中具有基因特征。基因表达包括多能性基因（SOX2、OCT4）、内胚层转录因子（如SOX9、SOX17、PDX1）、其他干细胞特征（如NCAM、CD44、碘化钠同向转运体或NIS）以及增殖生物标志物（Ki67）的代表性特征。当作为类器官移植到肝脏与胰腺上时，干/祖细胞在不同的体外条件下或体内的反应证明了肝/胰腺的多能性。因此，猪是利用这些干/祖细胞进行肝脏和胰腺功能障碍细胞治疗的转化/临床前研究的理想宿主。
