Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, People's Republic of China.
Translational Medical Center, Second Affiliated Hospital of Shantou University Medical College, 22 Xinling road, Shantou, Guangdong, 515041, People's Republic of China.
Cell Commun Signal. 2017 Oct 17;15(1):43. doi: 10.1186/s12964-017-0199-5.
We evaluated the therapeutic effect and fate of high doses of human umbilical cord Wharton jelly cells (hUCWJCs) after IP administration to streptozotocin (STZ)-induced diabetic mice.
Type 1 diabetes (T1D) was induced in Kunming mice via IP injection of STZ. hUCWJCs were labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). Diabetic animals with sustained hyperglycemia for at least 2 weeks were administered 1 × 10 Dil-hUCWJCs via intraperitoneal injection. Insulin, glucagon and PDX-1 were detected by immunofluorescence with confocal microscopy. Serum mouse and human C-peptide was assayed in blood collected via intracardiac puncture. Specific β-cell differentiation markers and human DNA were assessed using qPCR performed with 200 ng of target DNA.
hUCWJCs migrated to the STZ-damaged organs and contributed to lower blood glucose levels in 30% of the treated mice. Confocal microscopy revealed the presence of resident insulin-positive cells in the liver and kidneys. hUCWJC-treated mice with restored hyperglycemia also showed increased serum mouse C-peptide levels. The qPCR results, particularly in the liver, revealed that after transplantation hUCWJCs upregulated genes of endocrine precursors but failed to express endocrine stage markers. Mice with restored hyperglycemia had reduced urinary volume and lacked glomerular hypertrophy, exhibiting a morphology resembling that of normal glomeruli. Moreover, we also verified that one of the possible mechanisms by which hUCWJCs exert immunosuppressive effects is through down-regulation of the cell surface receptor HLA-1.
We confirmed the potential of IP administration of hUCWJCs and the capability of these cells to migrate to damaged tissues and promote insulin secretion from non-pancreatic local cells and to improve renal damage. These findings confer unique therapeutic properties to hUCWJCs, suggesting a promising future in the treatment of diabetes mellitus.
我们评估了高剂量人脐带华通氏胶细胞（hUCWJCs）经腹腔注射到链脲佐菌素（STZ）诱导的糖尿病小鼠后的治疗效果和命运。
通过腹腔注射 STZ 诱导昆明小鼠发生 1 型糖尿病（T1D）。用 1,1'-二辛基-3,3,3',3'-四甲基吲哚羰花青高氯酸盐（DiI）标记 hUCWJCs。对至少持续 2 周高血糖的糖尿病动物通过腹腔内注射给予 1×106 Dil-hUCWJCs。通过共聚焦显微镜用免疫荧光法检测胰岛素、胰高血糖素和 PDX-1。通过心内穿刺采集血液，检测血清小鼠和人 C 肽。使用 qPCR 检测 200ng 靶 DNA 评估特定的β细胞分化标志物和人 DNA。
hUCWJCs 迁移到 STZ 损伤的器官，并使 30%的治疗小鼠血糖水平降低。共聚焦显微镜显示，肝脏和肾脏中有常驻胰岛素阳性细胞。血糖恢复的 hUCWJC 治疗小鼠也显示血清小鼠 C 肽水平增加。qPCR 结果，特别是在肝脏中，显示移植后 hUCWJCs 上调内分泌前体细胞的基因，但未能表达内分泌阶段标志物。血糖恢复的小鼠尿排量减少，没有肾小球肥大，表现出类似于正常肾小球的形态。此外，我们还验证了 hUCWJCs 发挥免疫抑制作用的一种可能机制是通过下调细胞表面受体 HLA-1。
我们证实了腹腔内注射 hUCWJCs 的潜力，以及这些细胞迁移到受损组织并促进非胰腺局部细胞分泌胰岛素以及改善肾脏损伤的能力。这些发现赋予 hUCWJCs 独特的治疗特性，为糖尿病的治疗带来了广阔的前景。
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