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Long-term follow-up after non-myeloablative transplant of bone and marrow in BXSB mice

Department of Pediatrics, Walter Reed Army Medical Center, Georgia Avenue, NW, Washington DC, USA olcay.jones{at}gmail.com

A Lacson

Department of Laboratory Medicine and Pathology, University of Alberta Hospital, Mackenzie Health Sciences Centre. Edmonton, Alberta, Canada

X Zeng

R&D, SABiosciences Corporation, Executive Way, Frederick, MD, USA

JM Jones

Immunology Consultant, Potomac, MD, USA

K Katti

George Washington University School of Medicine, Washington, DC, USA

RA Cahill

Cardinal Glennon Hospital, South Grand Avenue, St. Louis, MO, USA

AA Ahmed

Department of Pathology and Laboratory Medicine, Children's Mercy Hospitals and Clinics, Gillham Road, Kansas City, MO, USA

We present long-term outcomes of BXSB mice after non-myeloablative bone marrow transplants using major histocompatability complex (MHC)-matched cells. Groups differed in sources of donor lymphocytes or mesenchymal stromal cells (MSC). Unfractionated marrow cells from green fluorescent protein (GFP) transgenic (Tg) mice (BMT group) or from RAG1–/– B6 mice (RAG group) were injected intravenously (i.v.) into irradiated (550 cGy) hosts. As a source of mesenchymal cells, bone chips from GFP-Tg were injected intraperitoneally alone (MSC group) or along with i.v. bone marrow cells (BMT + MSC group). Controls were untreated mice (UnTx) or mice exposed to radiation only (Rad Cont). At 62 weeks post-transplant, surviving mice were harvested for histopathology, flow cytometry and real time polymerase chain reaction (RT-PCR). The mice from BMT + MSC group had the best outcomes for survival rates (71.4% vs. 43.8%), renal scores (2.9% vs. 28.8% glomerular sclerosis) and percent splenic monocytes (4.2 vs. 11.3%) compared with mice from Rad Cont. Improvement in RAG and BMT groups was less prominent but were comparable with one another. Although MSC alone were not sufficient to control the renal pathology, it limited the expansion of CD4^–CD8^– T cell populations without a change in Foxp3 expression. The results suggest the importance of the innate immune system in disease pathogenesis and a role for MSC in immunomodulation.

Key Words: mesenchymal stromal cells • rodent • stem cell • systemic lupus erythematosus • transplantation

Lupus, Vol. 18, No. 9, 813-821 (2009)
DOI: 10.1177/0961203309104391


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