Transplantation of Adipose Tissue-Derived Mesenchymal Stem Cells Prevents the Development of Lupus Dermatitis.
MRL/lpr mice spontaneously develop high titers of anti-dsDNA antibodies and symptoms such as glomerular nephritis and organ weight gain. They also develop spontaneous skin inflammation similar to the cutaneous lesions common in human lupus erythematosus. This study aimed to compare the effects of long-term serial administration of human adipose tissue-derived mesenchymal stem cells (ASCs), CTLA4Ig-overexpressing ASCs, and cyclophosphamide treatment in MRL/lpr mice. MRL/lpr mice were divided into saline (C), cyclophosphamide (Y), ASC early (E), ASC late (L), and CTLA4Ig-overexpressing ASC (CT) treatment groups. Background-matched control MRL/MPJ mice treated with saline (N) were also compared. The treatment period was 5-23 weeks, except for the L group (15-23 weeks). Blood and tissue samples were collected when the mice were 24 weeks old. Organ weight, anti-dsDNA antibodies, urine protein, skin and kidney histologic abnormalities, and trabecular bone volume were evaluated. The Y group showed the greatest decrease in anti-dsDNA antibodies, organ weight, degree of kidney inflammation and glomerular infiltration of C3, and incidence rate of severe proteinuria; the E, L, and CT treatment groups showed better results than the C group. ASC transplantation reduced anti-dsDNA antibody levels significantly. Mice treated with ASCs or CTLA4Ig-ASCs starting from the early disease stage did not show dermatitis upon gross examination; they demonstrated significant improvement in hyperkeratosis, acanthosis, and inflammatory cell infiltration scores in histopathology. Micro-CT analysis revealed that cyclophosphamide treatment significantly decreased bone volume and increased bone spacing in the trabecular bone. Thus, we found that ASC and CTLA4-ASC treatments prevent lupus dermatitis development in MRL/lpr mice without adverse effects.
1 Laboratory Animal Research Center, Samsung Biomedical Research Institute , Seoul, Republic of Korea.|2 School of Medicine, Sungkyunkwan University , Seoul, Republic of Korea.
Eun Wha
EW
Choi
3 Biostar Stem Cell Research Center, K-STEMCELL , Seoul, Republic of Korea.
Il Seob
IS
Shin
1 Laboratory Animal Research Center, Samsung Biomedical Research Institute , Seoul, Republic of Korea.
Ji Woo
JW
Song
1 Laboratory Animal Research Center, Samsung Biomedical Research Institute , Seoul, Republic of Korea.
Tae Won
TW
Yun
1 Laboratory Animal Research Center, Samsung Biomedical Research Institute , Seoul, Republic of Korea.|2 School of Medicine, Sungkyunkwan University , Seoul, Republic of Korea.
Jehoon
J
Yang
1 Laboratory Animal Research Center, Samsung Biomedical Research Institute , Seoul, Republic of Korea.|2 School of Medicine, Sungkyunkwan University , Seoul, Republic of Korea.
Kyu-Sil
KS
Choi
4 Laboratory of Developmental Biology and Genomics, BK21 Program for Veterinary Science, Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University , Seoul, Republic of Korea.
Je Kyung
JK
Seong
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D003872:Dermatitis / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D019463:Mice, Inbred MRL lpr; D008815:Mice, Inbred Strains; D011507:Proteinuria / Q000378:metabolism