Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic mice
Abstract Background 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. Methods Type 1 diabetes (T1D) was induced in Kunming mice via IP injection of STZ. hUCWJCs were...
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doaj-160b713769d04d6484a3e577f004d7782020-11-24T22:24:01ZengBMCCell Communication and Signaling1478-811X2017-10-0115111310.1186/s12964-017-0199-5Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic miceMartin Maldonado0Tianhua Huang1Lujun Yang2Lan Xu3Lian Ma4Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical CollegeGuangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Research Center for Reproductive Medicine, Shantou University Medical CollegeTranslational Medical Center, Second Affiliated Hospital of Shantou University Medical CollegeGuangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Research Center for Reproductive Medicine, Shantou University Medical CollegeDepartment of Pediatrics, Second Affiliated Hospital of Shantou University Medical CollegeAbstract Background 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. Methods 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 × 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s12964-017-0199-5Human umbilical cord Wharton jelly cellsDiabetes type-1StreptozotocinIntraperitoneal administrationInsulin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Martin Maldonado Tianhua Huang Lujun Yang Lan Xu Lian Ma |
spellingShingle |
Martin Maldonado Tianhua Huang Lujun Yang Lan Xu Lian Ma Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic mice Cell Communication and Signaling Human umbilical cord Wharton jelly cells Diabetes type-1 Streptozotocin Intraperitoneal administration Insulin |
author_facet |
Martin Maldonado Tianhua Huang Lujun Yang Lan Xu Lian Ma |
author_sort |
Martin Maldonado |
title |
Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic mice |
title_short |
Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic mice |
title_full |
Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic mice |
title_fullStr |
Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic mice |
title_full_unstemmed |
Human umbilical cord Wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in STZ-induced diabetic mice |
title_sort |
human umbilical cord wharton jelly cells promote extra-pancreatic insulin formation and repair of renal damage in stz-induced diabetic mice |
publisher |
BMC |
series |
Cell Communication and Signaling |
issn |
1478-811X |
publishDate |
2017-10-01 |
description |
Abstract Background 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. Methods 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 × 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. Results 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. Conclusions 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. |
topic |
Human umbilical cord Wharton jelly cells Diabetes type-1 Streptozotocin Intraperitoneal administration Insulin |
url |
http://link.springer.com/article/10.1186/s12964-017-0199-5 |
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