Department of Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Department of General Surgery, Children's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, China.
Front Immunol. 2023 Jan 17;14:1084056. doi: 10.3389/fimmu.2023.1084056. eCollection 2023.
The contribution of bone-marrow derived cells (BMCs) to a newly formed beta-cell population in adults is controversial. Previous studies have only used models of bone marrow transplantation from sex-mismatched donors (or other models of genetic labeling) into recipient animals that had undergone irradiation. This approach suffers from the significant shortcoming of the off-target effects of irradiation. Partial pancreatic duct ligation (PDL) is a mouse model of acute pancreatitis with a modest increase in beta-cell number. However, the possibility that recruited BMCs in the inflamed pancreas may convert into beta-cells has not been examined. Here, we used an irradiation-free model to track the fate of the BMCs from the donor mice. A ROSA-mTmG red fluorescent mouse was surgically joined to an INS1 knock-in mouse by parabiosis to establish a mixed circulation. PDL was then performed in the INS1 mice 2 weeks after parabiosis, which was one week after establishment of the stable blood chimera. The contribution of red cells from ROSA-mTmG mice to beta-cells in INS1 mouse was evaluated based on red fluorescence, while cell fusion was evaluated by the presence of green fluorescence in beta-cells. We did not detect any red or green insulin+ cells in the INS1 mice, suggesting that there was no contribution of BMCs to the newly formed beta-cells, either by direct differentiation, or by cell fusion. Thus, the contribution of BMCs to beta-cells in the inflamed pancreas should be minimal, if any.
骨髓来源的细胞（BMCs）对成体中新形成的β细胞群体的贡献存在争议。以前的研究仅使用了来自性别不匹配供体的骨髓移植模型（或其他遗传标记模型）进入已经接受照射的受体动物。这种方法存在一个严重的缺点，即照射的脱靶效应。部分胰腺导管结扎（PDL）是一种急性胰腺炎的小鼠模型，β细胞数量适度增加。然而，尚未研究招募到的炎症胰腺中的 BMC 是否可以转化为β细胞。在这里，我们使用了一种无照射的模型来追踪供体小鼠的 BMC 命运。将 ROSA-mTmG 红色荧光小鼠通过并体手术与 INS1 基因敲入小鼠相连，建立混合循环。并体 2 周后，在 INS1 小鼠中进行 PDL，这是在稳定的血液嵌合体建立后 1 周。根据红色荧光评估来自 ROSA-mTmG 小鼠的 RBC 对 INS1 小鼠中β细胞的贡献，而通过β细胞中绿色荧光的存在评估细胞融合。我们在 INS1 小鼠中未检测到任何红色或绿色胰岛素+细胞，表明 BMC 对新形成的β细胞没有任何贡献，无论是直接分化还是细胞融合。因此，如果有的话，BMC 对炎症胰腺中β细胞的贡献应该是最小的。
