[Combined mesenchymal stem cells and allogenic bone marrow transplantation in treatment of MRL/lpr mice].
OBJECTIVE
In order to study the role of the bone marrow-derived mesenchymal stem cells (MSCs) transplanted with or without bone marrow (BM) in the treatment of lupus mice and the effect of MSCs in the onset of systemic lupus erythematosus (SLE).


METHODS
Twenty 12-week-old female MRL/lpr mice were randomly divided into four groups, including simple bone marrow transplantation group (SG, BM 1 x 10(7)), united group-1 (UG1, BM 1 x 10(7) + MSCs 1 x 10(4)), united group-2 (UG2, BM 1 x 10(7) + MSCs 1 x 10()6), the positive control group (PG, no transplantation). BALB/c mice were used as the negative control group (NG, no transplantation). MSCs which were amplified from the bone marrow of male BALB/c mice in vitro were transplanted into the female MRL/lpr mice with or without BM. One month later Y chromosome was detected to confirm if the transplantation was successful or not. The change of weight, white blood cells, urine protein, anti-dsDNA antibody, the pathology and immunofluorescence of renal were observed to evaluate the therapeutic efficacy.


RESULTS
Y chromosome was detected in all transplanted female mice. Compared with PG, urine protein concentration in SG, UG1 and UG2 significantly decreased 30 days after transplantation (P < 0.05). 40 days after transplantation, the tite of anti-dsDNA antibodies in SG (0.91 +/- 0.27) was still higher than NG, which OD value was 0.47 +/- 0.10 (P < 0.05), but there was no statistical difference among UG1 (0.76 +/- 0.28), UG2 (0.73 +/- 0.10) and NG (P > 0.05). However, 50 days after transplantation, there was no marked difference of the tite of anti-dsDNA antibodies in SG (0.55 +/- 0.15), UG1 (0.57 +/- 0.14) and UG2 (0.58 +/- 0.05) compared with NG (P > 0.05). After transplantation there was no vasculitis, no inflammatory cell infiltration in matrix and no obvious intercapillary cells proliferation in the kidney. The immunofluorescence became negative or weakly positive.


CONCLUSIONS
MSCs transplantation with or without BM can both improve the pathogenetic condition of MRL/lpr mice. MSCs can accelerate the clearance of anti-dsDNA antibody and promote the restoration of injured organs. We presume that MSCs are important immunological regulation cells in SLE.
Zhang
Guang-Feng
GF
Department of Rheumatism, Guangdong Provincial People's Hospital, Guangzhou 510080, China.
Zhang
Xiao
X
Dong
Guang-Fu
GF
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D016026:Bone Marrow Transplantation; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D014184:Transplantation, Homologous
D000974:Antibodies, Antinuclear; D004247:DNA