Improved function of circulating angiogenic cells is evident in type 1 diabetic islet-transplanted patients.
Circulating angiogenic cells (CACs) are vascular-committed bone marrow-derived cells that are dysfunctional in type 1 diabetes (T1D). Here we studied whether restoration of normoglycemia following islet transplantation is associated with better CAC function. We carried out a cross-sectional study of 18 T1D patients, 14 insulin-independent islet-transplanted patients (ITA) and 14 healthy controls (C) evaluating in vivo and in vitro CACs viability and function. We found that the percentage of CACs in vivo did not differ among the three groups while the number of CAC colonies obtained from T1D, but not from ITA, was reduced compared to C (C = 7.3 ± 1.9, T1D = 0.9 ± 0.4 and ITA = 4.7 ± 1.9; p < 0.05 T1D vs. all). In vitro CAC migration/differentiation were similar, while in vivo an improved angiogenic ability of ITA compared to T1D was shown (capillary density: C = 93.5 ± 22.1, T1D = 19.2 ± 2.8 and ITA = 44.0 ± 10.5, p < 0.05 T1D vs. all). Increased apoptosis and lesser IL-8 secretion were evident in CACs obtained from T1D compared to C and ITA. in vitro addition of anti-hIL-8 reduced the number of colonies obtained from C. Finally, T1D, but not ITA, had a lower endothelial-dependent dilatation (EDD) compared with C. These data suggest that CAC function is altered in T1D and may be improved after islet transplantation.
Transplantation Research Center, Children's Hospital, Harvard Medical School, Boston, MA, USA.
A
A
Petrelli
A
A
Maestroni
G P
GP
Fadini
D
D
Belloni
M
M
Venturini
M
M
Albiero
S
S
Kleffel
B G
BG
Mfarrej
A Del
AD
Maschio
P
P
Maffi
A
A
Avogaro
E
E
Ferrero
G
G
Zerbini
A
A
Secchi
P
P
Fiorina
D000328:Adult; D017209:Apoptosis; D001786:Blood Glucose / Q000502:physiology; D049109:Cell Proliferation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000601:surgery*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D007328:Insulin / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D007515:Islets of Langerhans / Q000098:blood supply; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D014463:Ultrasonography; D051028:bcl-2-Associated X Protein / Q000502:physiology; D051025:bcl-Associated Death Protein / Q000502:physiology
D001786:Blood Glucose; D007328:Insulin; D016209:Interleukin-8; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein