Waseem, Muhammad and Strutt, Brenda and . RAHMAN, ATTA UR and Salim, Asmat and Hill, David J (2015) Hypoxic Preconditioning of Adult Bone Marrow Mesenchymal Stem Cells Enhances Their Ability to Reverse Diabetes in Streptozotocin (STZ) Diabetic Mice. Hypoxic Preconditioning of Adult Bone Marrow Mesenchymal Stem Cells Enhances Their Ability to Reverse Diabetes in Streptozotocin (STZ) Diabetic Mice, 64 (1): 183-OR. ISSN 1939-327X
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We and others have previously shown that both bone marrow-derived mesenchymal (MSC) and hematopoietic stem cells (HSC) induce β-cell regeneration following grafting into diabetic mice. This study investigated the ontogeny of endogenous HSC and MSC within pancreas following treatment with STZ, as well as the effect of hypoxic pre-conditioning of exogenous young vs, adult MSC on β-cell regeneration. Vav-iCre; R26R transgenic mice were utilized where HSC and progeny express yellow fluorescent protein (YFP). MSC and HSC were visualized within pancreas by immunohistochemistry. Cells expressing YFP were present at all ages around islets and adjacent
to pancreatic ducts, and were located within the islets at days 40 and 130. MSC, detected with CD44, were associated predominantly within exocrine tissue at days 10 and 21, but were absent at older ages. Following
treatment with STZ at day 5, a 63% increase was found in HSC-derived cells within islets at day 40, concurrent with β-cell regeneration. A 58% increase in MSC was found at day 21 within exocrine tissue following STZ, compared
to saline-treated controls. MSCs derived from young (2-4 weeks) or adult (32-40 weeks) mice were rendered hypoxic by exposure to 0.5mM 2, 3-dinitrophenol for 10 min and re-oxygenated for 24 hr. Hypoxic or control MSCs were
transplanted into the STZ-diabetic mice via the tail vein. Regeneration of β-cells was confi rmed by a signifi cant decrease in glycemia and an increase in plasma insulin levels. Homing of MSCs to the pancreas was confi rmed by microscopy. MSC from young, but not adult mice restored insulin levels while reducing hyperglycemia, within 10 days. Hypoxic pre-conditioning of adult MSC rendered them comparable to those from young mice in the reversal of diabetes. Results suggest that endogenous MSC and HSC are both mobilized to the pancreas following β-cell damage, and that the therapeutic potential of adult MSC can be enhanced by hypoxic pre-conditioning.
| 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 06:41 |
| Last Modified: | 17 Jul 2020 06:43 |
| URI: | http://research.riphah.edu.pk/id/eprint/590 |
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