title: Allogeneic mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus: 4 years of experience.
abstract: Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitors and are capable of differentiating into several tissues of mesenchymal origin. We have shown that bone marrow-derived MSCs from both SLE patients and lupus-prone MRL/lpr mice are defective structurally and functionally. Here we observe the long-term safety and efficacy of allogeneic MSC transplantation (MSCT) in treatment-resistant SLE patients. Eighty-seven patients with persistently active SLE who were refractory to standard treatment or had life-threatening visceral involvement were enrolled. Allogeneic bone marrow or umbilical cord-derived MSCs were harvested and infused intravenously (1 × 10(6) cells/kg of body weight). Primary outcomes were rates of survival, disease remission and relapse, as well as transplantation-related adverse events. Secondary outcomes included SLE disease activity index (SLEDAI) and serologic features. During the 4-year follow-up and with a mean follow-up period of 27 months, the overall rate of survival was 94% (82/87). Complete clinical remission rate was 28% at 1 year (23/83), 31% at 2 years (12/39), 42% at 3 years (5/12), and 50% at 4 years (3/6). Rates of relapse were 12% (10/83) at 1 year, 18% (7/39) at 2 years, 17% (2/12) at 3 years, and 17% (1/6) at 4 years. The overall rate of relapse was 23% (20/87). Disease activity declined as revealed by significant changes in the SLEDAI score, levels of serum autoantibodies, albumin, and complements. A total of five patients (6%) died after MSCT from non-treatment-related events in the 4-year follow-up, and no transplantation-related adverse event was observed. Allogeneic MSCT resulted in the induction of clinical remission and improvement in organ dysfunction in drug-resistant SLE patients.
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, P. R. China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.forename: Huayong
authors.initials: H
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Xuebing
authors.initials: X
authors.lastname: Feng
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Bingzhu
authors.initials: B
authors.lastname: Hua
authors.forename: Bujun
authors.initials: B
authors.lastname: Liu
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.forename: Gary S
authors.initials: GS
authors.lastname: Gilkeson
authors.forename: Richard M
authors.initials: RM
authors.lastname: Silver
authors.forename: Wanjun
authors.initials: W
authors.lastname: Chen
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002648:Child; D003165:Complement System Proteins / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D012008:Recurrence; D012709:Serum Albumin / Q000378:metabolism; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D014470:Umbilical Cord / Q000166:cytology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D012709:Serum Albumin; D003165:Complement System Proteins