Vakilian Mehrdad, Ghaedi Kamran
Department of Cell Regeneration and Advanced Therapies, Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), University of Pablo de Olavide-University of Seville-CSIC, Sevilla, Spain; Department of Cell Biology, Genetics and Physiology, University of Malaga (UMA), The Institute of Biomedical Research in Malaga (IBIMA), Málaga, Spain.
Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science & Technology, University of Isfahan, Hezar Jerib Ave., Azadi Sq., Isfahan, Iran.
Gene. 2021 Jun 15;785:145607. doi: 10.1016/j.gene.2021.145607. Epub 2021 Mar 26.
Although lifelong renewal and additional compensatory growth in response to demand are undeniable facts, so far, no specific stem cells have been found for pancreatic cells. According to the consensus model, the development of pancreas results from the hierarchical differentiation of pluripotent stem cells towards the appearance of the first endocrine and exocrine cells at approximately 7.5 to 8th gestation week (GW) of human embryo. However, the primitive endocrine cells arising from the embryonic phase of development do not appear to be mature or fully functional. Asymmetric localization of cellular components, such as Numb, partition protein complexes (PAR), planar cell polarity components, and certain mRNAs on the apical and basal sides of epithelial cells, causes cellular polarization. According to our model, the equal distribution of cellular components during symmetric cell division yields similar daughter cells that are associated with duct expansion. In contrast, asymmetric cell division is associated with uneven distribution of cellular components among daughter cells, resulting in different fates. Asymmetric cell division leads to duct branching and the development of acinar and stellate cells by a daughter cell, as well as the development of islet progenitor cells through partial epithelial-to-mesenchymal transition (EMT) and delamination of another daughter cell. Recently, we have developed an efficient method to obtain insulin-secreting cells from the transdifferentiation of hESC-derived ductal cells inducing a partial EMT by treatment with Wnt3A and activin A in a hypoxic environment. Similar models can be offered for other tissues and organs such as mammary glands, lungs, prostate, liver, etc. This model may open a new horizon in the field of regenerative medicine and be useful in explaining the cause of certain abnormalities, such as the occurrence of certain cysts and tumors.
尽管终身更新以及根据需求进行额外的代偿性生长是不可否认的事实，但到目前为止，尚未发现胰腺细胞的特定干细胞。根据公认的模型，胰腺的发育源于多能干细胞的分级分化，在人类胚胎妊娠约7.5至8周时出现第一批内分泌和外分泌细胞。然而，发育胚胎期产生的原始内分泌细胞似乎并不成熟或功能不全。细胞成分（如Numb、分隔蛋白复合物（PAR）、平面细胞极性成分和某些mRNA）在上皮细胞顶端和基底侧的不对称定位会导致细胞极化。根据我们的模型，对称细胞分裂过程中细胞成分的均匀分布产生了与导管扩张相关的相似子细胞。相反，不对称细胞分裂与子细胞间细胞成分的不均匀分布相关，导致不同的命运。不对称细胞分裂导致一个子细胞形成导管分支以及腺泡和星状细胞的发育，另一个子细胞通过部分上皮-间充质转化（EMT）和脱层形成胰岛祖细胞。最近，我们开发了一种有效的方法，通过在低氧环境中用Wnt3A和激活素A处理诱导hESC来源的导管细胞进行部分EMT转分化来获得胰岛素分泌细胞。其他组织和器官（如乳腺、肺、前列腺、肝脏等）也可以提供类似的模型。该模型可能为再生医学领域开辟新的视野，并有助于解释某些异常情况的原因，如某些囊肿和肿瘤的发生。
