Overi Diletta, Carpino Guido, Moretti Marta, Franchitto Antonio, Nevi Lorenzo, Onori Paolo, De Smaele Enrico, Federici Luca, Santorelli Daniele, Maroder Marella, Reid Lola M, Cardinale Vincenzo, Alvaro Domenico, Gaudio Eugenio
Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy.
Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Rome, Italy.
Front Cell Dev Biol. 2022 Feb 4;10:814165. doi: 10.3389/fcell.2022.814165. eCollection 2022.
Contrasting evidence is present regarding the contribution of stem/progenitor cell populations to pancreatic regeneration in diabetes. Interestingly, a cell compartment with stem/progenitor cell features has been identified in the pancreatic duct glands (PDGs). The aims of the present study were to evaluate pancreatic islet injury and regeneration, and the participation of the PDG compartment in type 2 diabetic mellitus (T2DM) and in an experimental model of diabetes. Human pancreata were obtained from normal (N = 5) or T2DM (N = 10) cadaveric organ donors. Experimental diabetes was generated in mice by intraperitoneal injection of 150 mg/kg of streptozotocin (STZ, N = 10); N = 10 STZ mice also received daily intraperitoneal injections of 100 µg of human recombinant PDX1 peptide (STZ + PDX1). Samples were examined by immunohistochemistry/immunofluorescence or RT-qPCR. Serum glucose and c-peptide levels were measured in mice. Islets in T2DM patients showed β-cell loss, signs of injury and proliferation, and a higher proportion of central islets. PDGs in T2DM patients had a higher percentage of proliferating and insulin or glucagon cells compared to controls; pancreatic islets could be observed within pancreatic duct walls of T2DM patients. STZ mice were characterized by reduced islet area compared to controls. PDX1 treatment increased islet area and the percentage of central islets compared to untreated STZ mice but did not revert diabetes. In conclusion, T2DM patients show signs of pancreatic islet regeneration and involvement of the PDG niche. PDX1 administration could support increased endocrine pancreatic regeneration in STZ. These findings contribute to defining the role and participation of stem/progenitor cell compartments within the pancreas.
关于干细胞/祖细胞群体对糖尿病胰腺再生的贡献，存在相互矛盾的证据。有趣的是，在胰腺导管腺（PDG）中已鉴定出具有干细胞/祖细胞特征的细胞区室。本研究的目的是评估胰岛损伤与再生，以及PDG区室在2型糖尿病（T2DM）和糖尿病实验模型中的参与情况。从正常（N = 5）或T2DM（N = 10）尸体器官供体获取人类胰腺。通过腹腔注射150 mg/kg链脲佐菌素（STZ，N = 10）在小鼠中诱导实验性糖尿病；10只STZ小鼠还每日腹腔注射100 μg人重组PDX1肽（STZ + PDX1）。通过免疫组织化学/免疫荧光或RT-qPCR检查样本。测量小鼠的血清葡萄糖和C肽水平。T2DM患者的胰岛显示β细胞丢失、损伤和增殖迹象，以及较高比例的中央胰岛。与对照组相比，T2DM患者的PDG中增殖细胞以及胰岛素或胰高血糖素细胞的百分比更高；在T2DM患者的胰腺导管壁内可观察到胰岛。与对照组相比，STZ小鼠的特征是胰岛面积减小。与未治疗的STZ小鼠相比，PDX1治疗增加了胰岛面积和中央胰岛的百分比，但未逆转糖尿病。总之，T2DM患者显示出胰岛再生和PDG微环境参与的迹象。给予PDX1可支持STZ诱导的内分泌胰腺再生增加。这些发现有助于明确胰腺内干细胞/祖细胞区室的作用和参与情况。
