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Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic mice

Authors
  • Maldonado, Martin1, 2, 3, 4
  • Huang, Tianhua3, 4
  • Yang, Lujun2, 5
  • Xu, Lan3
  • Ma, Lian1, 2, 6, 7
  • 1 Second Affiliated Hospital of Shantou University Medical College, Department of Pediatrics, Shantou, Guangdong, 515041, People’s Republic of China , Shantou (China)
  • 2 Second Affiliated Hospital of Shantou University Medical College, Translational Medical Center, 22 Xinling road, Shantou, Guangdong, 515041, People’s Republic of China , Shantou (China)
  • 3 Shantou University Medical College, Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Research Center for Reproductive Medicine, Shantou, 515041, People’s Republic of China , Shantou (China)
  • 4 Chengdu Jinjiang Hospital for Maternal & Child Health Care, Reproductive Medicine & Genetics, Chengdu, 610066, China , Chengdu (China)
  • 5 Second Affiliated Hospital of Shantou University Medical College, Department of Burns and Plastic Surgery, Shantou, Guangdong, 515041, People’s Republic of China , Shantou (China)
  • 6 Maternal and Child Health Care Hospital of Shenzhen University, Department of Pediatrics, Shenzhen, Guangdong, 518052, People’s Republic of China , Shenzhen (China)
  • 7 Maternal and Child Health Care Hospital of Pingshan District, Department of Pediatrics, Shenzhen, Guangdong, 518122, People’s Republic of China , Shenzhen (China)
Type
Published Article
Journal
Cell Communication and Signaling
Publisher
BioMed Central
Publication Date
Oct 17, 2017
Volume
15
Issue
1
Identifiers
DOI: 10.1186/s12964-017-0199-5
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundWe 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.MethodsType 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 × 107 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.ResultshUCWJCs 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.ConclusionsWe 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.

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