Direct comparison of the abilities of bone marrow mesenchymal versus hematopoietic stem cells to reverse hyperglycemia in diabetic NOD.SCID mice

Arany, Edith J and Waseem, Muhammad and Strutt, Brenda j and Reig, Astrid Chamson and Bernardo, Adam and Eng, Elizabeth and Hill, David J (2018) Direct comparison of the abilities of bone marrow mesenchymal versus hematopoietic stem cells to reverse hyperglycemia in diabetic NOD.SCID mice. Islets, 10 (4). pp. 137-150. ISSN 1938-2022

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Abstract

Both bone marrow-derived hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC)
improve glycemic control in diabetic mice, but their kinetics and associated changes in pancreatic
morphology have not been directly compared. Our goal was to examine the time course of
improvements in glucose tolerance and associated changes in β-cell mass and proliferation
following transplantation of equivalent numbers of HSC or MSC from the same bone marrow
into diabetic non-obese diabetic severe combined immune deficiency (NOD.SCID) mice. We used
transgenic mice with a targeted expression of yellow fluorescent protein (YFP) driven by the Vav1
gene promoter to genetically tag HSC and progeny. HSC were separated from bone marrow by
fluorescence-activated cell sorting and MSC following cell culture. Equivalent numbers of isolated
HSC or MSC were transplanted directly into the pancreas of NOD.SCID mice previously made
diabetic with streptozotocin. Glucose tolerance, serum insulin, β-cell mass and β-cell proliferation
were examined up to 28 days following transplant. Transplantation with MSC improved glucose
tolerance within 7 days and serum insulin levels increased, but with no increase in β-cell mass.
Mice transplanted with HSC showed improved glucose tolerance only after 3 weeks associated
with increased β-cell proliferation and mass. We conclude that single injections of either MSC or
HSC transiently improved glycemic control in diabetic NOD.SCID mice, but with different time
courses. However, only HSC infiltrated the islets and were associated with an expanded β-cell
mass. This suggests that MSC and HSC have differing mechanisms of action.

Item Type: Article
Subjects: Q Science > QP Physiology
Divisions: Faculty of Rehabilitation and Allied Health Sciences(FRAHS) > Riphah College of Rehabiliation and Allied Sciences Islamabad
Depositing User: Dr Muhammad Waseem
Date Deposited: 17 Jul 2020 06:45
Last Modified: 17 Jul 2020 06:45
URI: http://research.riphah.edu.pk/id/eprint/554

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