Powell Connor J, Singer Hani D, Juarez Ashley R, Kim Ryan T, Kim Elane, Payzin-Dogru Duygu, Savage Aaron M, Lopez Noah J, Thornton Kara, Blair Steven J, Abouelela Adnan, Dittrich Anita, Akeson Stuart G, Jain Miten, Whited Jessica L
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.
Department of Bioengineering, Northeastern University, Boston, Massachusetts, USA.
Dev Dyn. 2025 Jul 18. doi: 10.1002/dvdy.70060.
Diabetes is a condition characterized by a loss of pancreatic β-cell function, which results in the dysregulation of insulin homeostasis. Using a partial pancreatectomy model in axolotl, we aimed to observe the pancreatic response to injury.
Here we show a comprehensive histological characterization of pancreatic islets in axolotl. Following pancreatic injury, no apparent blastema-like structure was observed. We found a significant, organ-wide increase in cellular proliferation post-resection in the pancreas compared to sham-operated controls. This proliferative response was most robust at the site of injury. Further, an increase in nuclear density was observed, suggesting compensatory congestion as a mechanism of regeneration. We found that β-cells actively contributed to the increased rates of proliferation upon injury. β-Cell proliferation manifested in increased β-cell mass in injured tissue at 2 weeks post-injury. At 4 weeks post-injury, we found organ-wide proliferation to be extinguished while proliferation at the injury site persisted, corresponding to pancreatic tissue recovery. Similarly, total β-cell mass was comparable to sham after 4 weeks.
Our findings suggest a non-blastema-mediated regeneration process takes place in the pancreas, by which pancreatic resection induces whole-organ β-cell proliferation without the formation of a blastemal structure. This process is analogous to other models of compensatory congestion in axolotl.
糖尿病是一种以胰腺β细胞功能丧失为特征的疾病,这会导致胰岛素稳态失调。我们利用蝾螈的部分胰腺切除术模型,旨在观察胰腺对损伤的反应。
在此我们展示了蝾螈胰岛的全面组织学特征。胰腺损伤后,未观察到明显的芽基样结构。我们发现,与假手术对照组相比,胰腺切除术后胰腺中细胞增殖在全器官范围内显著增加。这种增殖反应在损伤部位最为强烈。此外,观察到核密度增加,提示代偿性充血是一种再生机制。我们发现β细胞在损伤后积极促进增殖率的提高。损伤后2周,β细胞增殖表现为损伤组织中β细胞质量增加。损伤后4周,我们发现全器官增殖停止,而损伤部位的增殖持续存在,这与胰腺组织恢复相对应。同样,4周后总的β细胞质量与假手术组相当。
我们的研究结果表明,胰腺中发生了一种非芽基介导的再生过程,通过该过程胰腺切除诱导全器官β细胞增殖,而不形成芽基结构。这一过程类似于蝾螈中其他代偿性充血模型。