Bhardwaj Gurprit, Vakani Mitul, Srivastava Abhay, Rawal Komal, Kalathil Amrita, Gupta Sarita
Molecular Endocrinology and Stem Cell Research Laboratory, Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390021, India.
Molecular Endocrinology and Stem Cell Research Laboratory, Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, 390021, India.
Exp Cell Res. 2022 Jan 15;410(2):112970. doi: 10.1016/j.yexcr.2021.112970. Epub 2021 Dec 9.
Islet integrity plays a major role in maintaining glucose homeostasis and thus replenishment of damaged islets by differentiation of resident endocrine progenitors into neo islets regulates the islet functionality. Islet differentiation is affected by many factors including crosstalk with various organs by secretome. Adipose derived stem cells (ADSC) secrete a large array of factors in the extracellular milieu that exhibit regulatory effects on other tissues including pancreatic islets. The microenvironment of metabolically compromised human ADSCs (hADSCs) has a detrimental impact on islet functionality. In the present study, the role of secretome was studied on the differentiation of islets. Expression of key transcription factors like HNF-3B, NGN-3, NeuroD, PDX- 1, Maf-A, and GLUT-2 involved in development were differentially regulated in obese hADSC secretome as compared to control hADSC secretome. Islet like cell clusters (ILCCs) functionality and viability were critically hampered under obese hADSC secretome with compromised yield, morphometry, lower expression of C-peptide and Glucagon as well as higher ROS activity and cell death parameters. This study provides considerable insights on two major findings which are (i) exploring the use of hADSC secretome in islet differentiation and (ii) understanding the regulating effect of altered hADSC secretome under a metabolically compromised condition.
胰岛完整性在维持葡萄糖稳态中起主要作用，因此通过将驻留的内分泌祖细胞分化为新胰岛来补充受损胰岛可调节胰岛功能。胰岛分化受多种因素影响，包括通过分泌组与各种器官的相互作用。脂肪来源干细胞（ADSC）在细胞外环境中分泌大量因子，这些因子对包括胰岛在内的其他组织具有调节作用。代谢受损的人脂肪来源干细胞（hADSC）的微环境对胰岛功能有不利影响。在本研究中，研究了分泌组在胰岛分化中的作用。与对照hADSC分泌组相比，肥胖hADSC分泌组中参与发育的关键转录因子如HNF-3B、NGN-3、NeuroD、PDX-1、Maf-A和GLUT-2的表达受到差异调节。在肥胖hADSC分泌组下，胰岛样细胞簇（ILCC）的功能和活力受到严重阻碍，产量、形态测量、C肽和胰高血糖素表达降低，以及活性氧活性和细胞死亡参数升高。本研究为两个主要发现提供了重要见解，即（i）探索hADSC分泌组在胰岛分化中的应用，以及（ii）了解代谢受损条件下改变的hADSC分泌组的调节作用。
