Distinct characteristics and features of allogeneic chimerism in the NOD mouse model of autoimmune diabetes.
The adaptation of allogeneic chimerism in treatment of autoimmune diabetes has been shown as a promising approach in numerous studies in both experimental and clinical settings. Establishment of hemopoietic chimerism in NOD mice is the most adequate animal model to study mechanisms involved in the multiple aspects of the curative effects of chimerism in autoimmunity-prone individuals. However, there are some discrepancies in the current literature for parameters and criteria used to characterize chimerism in the NOD model. This study was aimed to standardize the criteria for the different pathological stages of diabetogenesis in chimeric versus unmanipulated NOD mice. We report two well-defined scoring systems and a new Index N for the assessment of the pathological characteristics of diabetogenesis and GVHD in chimeric NOD mice. Also, we have demonstrated that, in the NOD model, recipient conditioning resulting in as low as 1% of chimerism is sufficient to promote engraftment of the BM donor-specific islets of Langerhans.
Zorina
Tatiana D
TD
Department of Pediatrics, University of Pittsburgh, School of Medicine, PA 15213, USA. tatiana@pitt.edu
Subbotin
Vladimir M
VM
Bertera
Suzanne
S
Alexander
Angela M
AM
Haluszczak
Catherine
C
Styche
Alexis J
AJ
Trucco
Massimo
M
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000639:trends; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics* / Q000517:prevention & control; D007249:Inflammation / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000639:trends; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018183:Transplantation Chimera / Q000235:genetics* / Q000378:metabolism; D014184:Transplantation, Homologous / Q000379:methods* / Q000639:trends