Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Xiubo Fan1, Shane Goh Ee1, Francesca Wei Inng Lim2, Sudipto Bari3, Tony Kiat Hon Lim1, Shang Li1 and William Ying Khee Hwang2,3,4
1Singapore General Hospital, Singapore 2Duke-NUS Graduate Medical School, Singapore 3National University of Singapore, Singapore 4Singapore Cord Blood Bank, Singapore
Scientific Tracks Abstracts: J Clin Cell Immunol
In vitro, the effect of mesenchymal stromal cell (MSC) on immune suppression has been well studied. However, in vivo, questions regarding MSC optimal therapeutic strategy, homing, survival, and timing for immune suppression are still elusive. To address these questions for systemic lupus erythematosus (SLE), autoimmune lymphoproliferative syndrome (ALPS) and Sjogren�s syndrome, a MLR/MpJ-Faslpr/J (Faslpr) mice model was employed. Multipotency of bone marrow derived MSC (BM-MSC) was determined by phenotypic analysis and multipotential differentiation assay. Four- to six-month-old Faslpr mice showed onset of autoimmune disease with lymphoproliferation. Optimal infusion dose was determined by serial dilution. Homing and survival of MSC were monitored by fluorescent microscopy. Infusion frequency was deduced from immunomodulatory kinetics study. BM-MSC with passage number less than 10 could properly maintain multi-lineage differentiation capacity and stem cell phenotypes. Eight rounds administration of 10��106 cells/kg BM-MSC improved mouse survival from 62.5% to 92.9% and reversed lymphoproliferation to normal levels at day-21 post-transplantation (PT) (p=0.189). BM-MSC mainly and eventually homed to immune organs at four months PT. Immunomodulatory kinetics showed that the optimal immunosuppression period of BM-MSC occurred from day-7 to day-21 PT in immune organs, lung, and kidney; hence, optimal infusion frequency was deduced as 21 days. In conclusion, an appropriate therapeutic strategy in a pre-clinical autoimmune disease mouse model was established with a defined MSC source as well as optimal infusion dose, frequency, and administration number. It will help to standardize cell preparation, characterization and administration protocol, and minimize the outcome discrepancies between different centers worldwide.
Xiubo Fan has completed her PhD from Dalian University of Technology in 2008 and worked as Research Scientist in Singapore General Hospital, Singapore since then. She has published 14 papers in international peer reviewed journals and has been serving as an Editorial Board Member of Autoimmune Diseases and Therapeutic Approaches.
Email: fan.xiubo@sgh.com.sg