A Long-Term Follow-Up Study of Allogeneic Mesenchymal Stem/Stromal Cell Transplantation in Patients with Drug-Resistant Systemic Lupus Erythematosus

Dandan Wang, Huayong Zhang, Jun Liang, Hong Wang, Bingzhu Hua, Xuebing Feng, Gary S Gilkeson, Dominique Farge, Songtao Shi, Lingyun Sun, Dandan Wang, Huayong Zhang, Jun Liang, Hong Wang, Bingzhu Hua, Xuebing Feng, Gary S Gilkeson, Dominique Farge, Songtao Shi, Lingyun Sun

Abstract

Allogeneic mesenchymal stem/stromal cells (MSCs) have been widely studied as an alternative cell source for regenerative medicine. Here, we report a long-term follow-up study of allogeneic bone marrow and/or umbilical cord MSC transplantation (MSCT) in severe and drug-refractory systemic lupus erythematosus (SLE) patients. Eighty-one patients were enrolled, and the 5-year overall survival rate was 84% (68/81) after MSCT. At 5-year follow-up, 27% of patients (22/81) were in complete clinical remission and another 7% (6/81) were in partial clinical remission, with a 5-year disease remission rate of 34% (28/81). In total, 37 patients had achieved clinical remission and then 9 patients subsequently relapsed, with 5-year overall rate of relapse of 24% (9/37). SLE Disease Activity Index scores, serum albumin, complement C3, peripheral white blood cell, and platelet numbers, as well as proteinuria levels, continued to improve during the follow-up. Our results demonstrated that allogeneic MSCT is safe and resulted in long-term clinical remission in SLE patients.

Keywords: bone marrow; mesenchymal stem cells; safety; systemic lupus erythematosus; umbilical cord.

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Patient Survival and Clinical Remission after Mesenchymal Stem/Stromal Cell Transplantation Probability of overall survival (A) and complete clinical remission (B) in lupus patients undergoing mesenchymal stem/stromal cell transplantation (MSCT), by Kaplan-Meier survival analysis.
Figure 2
Figure 2
Disease Activity and Serologic Changes Before and After Mesenchymal Stem/Stromal Cell Transplantation SLE Disease Activity Index score significantly decreased (A), and serum albumin (B) complement 3 (C3; C), and serum complement 4 (C4; D) increased, but with no significant difference compared with pre-MSCT levels.
Figure 3
Figure 3
Changes of Proteinuria and Renal Function Before and After Mesenchymal Stem/Stromal Cell Transplantation Twenty-four hour proteinuria significantly decreased at 1, 2, 3, 4, 5, 6, 7, and 8 years’ follow-up (A). Serum urea nitrogen (B), creatinine (C), and urine acid (D) showed no significant change before versus after MSCT.
Figure 4
Figure 4
Changes of Hematologic Indices Before and After Mesenchymal Stem/Stromal Cell Transplantation Peripheral white blood cell count significantly increased at 1, 2, 3, 4, 5, and 6 years’ follow-up (A). Levels of hemoglobin increased, with statistical significance at 2 years (B). Peripheral blood platelet number was significantly elevated at 2, 3, and 5 years’ follow-up (C).

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