Genetically modified human bone marrow derived mesenchymal stem cells for improving the outcome of human islet transplantation.

Vaibhav Mundra, Hao Wu, Ram I Mahato

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The objective of this study was to determine the potential of human bone marrow derived mesenchymal stem cells (hBMSCs) as gene carriers for improving the outcome of human islet transplantation. hBMSCs were characterized for the expression of phenotypic markers and transduced with Adv-hVEGF-hIL-1Ra to overexpress human vascular endothelial growth factor (hVEGF) and human interleukin-1 receptor antagonist (hIL-1Ra). Human islets were co-cultured with hBMSCs overexpressing hVEGF and hIL-1Ra. Islet viability was determined by membrane fluorescent method and glucose stimulation test. Transduced hBMSCs and human islets were co-transplanted under the kidney capsule of NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) diabetic mice and blood glucose levels were measured over time to demonstrate the efficacy of genetically modified hBMSCs. At the end of study, immunofluorescent staining of kidney section bearing islets was performed for insulin and von Willebrand Factor (vWF). hBMSCs were positive for the expression of CD73, CD90, CD105, CD146 and Stro-1 surface markers as determined by flow cytometry. Transduction of hBMSCs with adenovirus did not affect their stemness and differentiation potential as confirmed by mRNA levels of stem cell markers and adipogenic differentiation of transduced hBMSCs. hBMSCs were efficiently transduced with Adv-hVEGF-hIL-1Ra to overexpress hVEGF and hIL-1Ra. Live dead cell staining and glucose stimulation test have shown that transduced hBMSCs improved the viability of islets against cytokine cocktail. Co-transplantation of human islets with genetically modified hBMSCs improved the glycemic control of diabetic NSG mice as determined by mean blood glucose levels and intraperitoneal glucose tolerance test. Immunofluorescent staining of kidney sections was positive for human insulin and vWF. In conclusion, our results have demonstrated that hBMSCs may be used as gene carriers and nursing cells to improve the outcome of islet transplantation.

Original languageEnglish (US)
JournalPloS one
Volume8
Issue number10
DOIs
StatePublished - 2013

Fingerprint

Islets of Langerhans Transplantation
Stem cells
Mesenchymal Stromal Cells
bone marrow
stem cells
Bone
Bone Marrow
Interleukin-1 Receptors
vascular endothelial growth factors
interleukin-1
von Willebrand Factor
antagonists
Glucose
Blood Glucose
Bearings (structural)
Genes
receptors
Insulin
Staining and Labeling
blood coagulation factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Genetically modified human bone marrow derived mesenchymal stem cells for improving the outcome of human islet transplantation. / Mundra, Vaibhav; Wu, Hao; Mahato, Ram I.

In: PloS one, Vol. 8, No. 10, 2013.

Research output: Contribution to journalArticle

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