Characterization of endothelial progenitor cells in the NOD mouse as a source for cell therapies.
BACKGROUND
Endothelial progenitor cells (EPCs) in bone marrow (BM) and peripheral blood (PB) contribute to tissue repair in various pathological conditions via the formation of new blood vessels. Previous studies indicate that diabetic patients have reduced EPC number and deregulated EPC function, although the regenerative properties of EPCs in diabetes are unknown. We wish to characterize and compare EPCs from pre-diabetic and diabetic non-obese diabetic (NOD) mice, a model of type 1 diabetes (T1D), in order to delineate the role of these cells in the pathogenesis of autoimmune diabetes.


METHODS
Whole BM was obtained by flushing femurs, tibias and illiac crests from pre-diabetic and diabetic NOD mice (5-30 weeks) in which the diabetic status was confirmed by measuring blood glucose levels (> or =11.5 mmol/L); PB was collected in heparin-coated tubes and lysed after incubation with antibodies directed against EPCs.


RESULTS
FACS analyses revealed a significant decrease in EPC number (CD31(+), c-Kit(+), Sca-1(+), Lin(-)) in BM from diabetic compared to pre-diabetic mice (P = 0.02). Conversely, EPC number was significantly increased in PB from diabetic compared to pre-diabetic mice (P = 0.01).


CONCLUSIONS
These data suggest that at the onset of diabetes, BM-derived EPCs are stimulated to enter the systemic circulation likely in response to signals from the pancreas. Further studies are required to elucidate whether EPCs home the damaged pancreas, thus representing a prospective source of autologous cells for beta-cell regeneration therapy.
Khoo
Cheen Peen
CP
Queen Mary's School of Medicine and Dentistry of London, Centre for Diabetes and Metabolic Medicine, London, UK.
Valorani
M G
MG
Brittan
Mairi
M
Alison
Malcolm R
MR
Warnes
Gary
G
Johansson
Ulrika
U
Hawa
Mohammed
M
Pozzilli
Paolo
P
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology; D002452:Cell Count; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology* / Q000473:pathology; D005260:Female; D005269:Femur; D005434:Flow Cytometry; D007085:Ilium; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018919:Neovascularization, Physiologic; D011236:Prediabetic State / Q000473:pathology; D013234:Stem Cells / Q000166:cytology* / Q000473:pathology; D013977:Tibia