Waseem, Muhammad and Arony, Edith J and Strutt, Brenda and Hill, David J (2015) Comparison and effect of age on the beta cell regenerative potential of bone-marrowderived mesenchymal (MSC) and haematopoietic stem cells (HSC) in mice. Comparison and effect of age on the beta cell regenerative potential of bone-marrowderived mesenchymal (MSC) and haematopoietic stem cells (HSC) in mice, 32 (S1). i-iii. ISSN 0742-3071
Full text not available from this repository.Abstract
Objectives: Bone-marrow-derived MSC and HSC both induce
beta cell regeneration following grafting into diabetic mice, but direct comparisons and changes with age have not been studied. We compared marrow stem cells grafted from young vs adult mice into diabetic recipients and how endogenous MSC/HSC change within the pancreas following beta cell injury.
Methods: We utilised transgenic mice where HSC express the genetic tag YFP. MSC were identified by CD44 expression. Fluorescence-activated cell separated marrow-derived HSC and MSC were harvested from young (2–4 weeks) or adult (34–38 weeks) mice and injected intra-pancreas into young, streptozotocin (STZ) diabetic NODscid recipients, with subsequent examination of glucose tolerance (IGTT), beta cell mass and retention of
grafted cells (immunohistochemistry). Endogenous pancreatic HSC and MSC distributions were measured in non-grafted mice following neonatal STZ.
Results: Hyperglycaemia and plasma insulin improved in diabetic mice 21–40 days after grafting with either HSC or MSC from young donors (glucose 8.7 � 0.4mM vs 19.5 � 0.9mM, n=6, p < 0.01; insulin 0.43 � 0.09ng/ml vs 0.22 � 0.01ng/ml, p < 0.01) vs sham grafted controls. IGTT was improved following stem cell grafting (area under the curve 610 � 135 vs 1450 � 489, p < 0.05) as was beta cell mass (16 � 5% increase, p < 0.05). Grafted stem cells were retained within the pancreas. Importantly, neither HSC nor MSC from adult donors were effective. Endogenous HSC were increased 63% within regenerating islets after STZ, whilst MSC increased by 58% but
in exocrine tissue.
Conclusions: Both MSC and HSC from young but not adult mice can induce beta cell regeneration. Endogenous HSC and MSC are mobilised following beta cell damage to different pancreatic compartments, perhaps reflecting separate 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 06:43 |
| Last Modified: | 17 Jul 2020 06:43 |
| URI: | http://research.riphah.edu.pk/id/eprint/589 |
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