Umbilical cord-derived mesenchymal stem cell transplantation (UC-MSCT) has been proved to be effective in the treatment of systemic lupus erythematosus (SLE), based on animal experiments and clinical trials. Diffuse alveolar hemorrhage (DAH) is a rare complication of SLE with a high mortality usually over 50%. This study aimed to assess the efficacy of UC-MSCT in the treatment of SLE-associated DAH. Four SLE patients complicated with DAH, who underwent UC-MSCT, were included. Clinical changes before and after transplantation were assessed by measurements of hemoglobin, platelet level, oxygen saturation, and serological factors. High-resolution CT (HRCT) scans of the chest were performed to evaluate pulmonary manifestation. All the four patients showed dramatic improvements of their clinical manifestations. Hemoglobin was elevated after UC-MSCT and was sustained at a normal level 6 months after UC-MSCT in the four patients. Platelet level was upregulated in two patients who had thrombocytopenia at baseline. Oxygen saturation appeared to be normal at 1 month after UC-MSCT, and this result was confirmed by the HRCT scan of the chest. Serum albumin elevated to 3.5 g/dl 6 months after transplantation. Our findings suggest that UC-MSCT results in amelioration of oxygen saturation as well as hematological and serologic changes, which revealed that UC-MSCT could be applied as a salvage strategy for DAH patients.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Chang MY, Fang JT, Chen YC et al (2002) Diffuse alveolar hemorrhage in systemic lupus erythematosus: a single center retrospective study in Taiwan. Ren Fail 24:791–802
Canas C, Tobon GJ, Granados M et al (2007) Diffuse alveolar hemorrhage in Colombian patients with systemic lupus erythematosus. Clin Rheumatol 26:1947–1949
Shen M, Zeng X, Tian X et al (2010) Diffuse alveolar hemorrhage in systemic lupus erythematosus: a retrospective study in China. Lupus 19:1326–1330
Kwok SK, Moon SJ, Ju JH et al (2011) Diffuse alveolar hemorrhage in systemic lupus erythematosus: risk factors and clinical outcome: results from affiliated hospitals of Catholic University of Korea. Lupus 20:102–107
Martinez-Martinez MU, Abud-Mendoza C (2011) Predictors of mortality in diffuse alveolar haemorrhage associated with systemic lupus erythematosus. Lupus 20:568–574
Hughson MD, He Z, Henegar J et al (2001) Alveolar hemorrhage and renal microangiopathy in systemic lupus erythematosus: immune complex small vascular injury with apoptosis. Arch Pathol Lab Med 125:475–483
Santos-Ocampo AS, Mandell BF, Fessler BJ (2000) Alveolar hemorrhage in systemic lupus erythematosus. Chest 118:1083–1090
Badsha H, The CL, Kong KO et al (2003) Pulmonary hemorrhage in systemic lupus erythematosus. Semin Arthritis Rheum 33:414–421
Nellessen CM, Poge U, Brensing KA et al (2008) Diffuse alveolar haemorrhage in a systemic lupus erythematosus patient successfully treated with rituximab: a case report. Nephrol Dial Transplant 23:385–386
Narshi CB, Haider S, Ford CM et al (2010) Rituximab as early therapy for pulmonary haemorrhage in systemic lupus erythematosus. Rheumatology 49:392–394
Pottier V, Pierrot M, Subra JF et al (2011) Successful rituximab therapy in a lupus patient with diffuse alveolar haemorrhage. Lupus 20:656–659
Young HE, Mancini ML, Wright RP et al (1995) Mesenchymal stem cells reside within the connective tissues of many organs. Dev Dyn 202:137–144
Williams JT, Southerland SS, Souza J et al (1999) Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. Am Surg 65:22–26
Zuk PA, Zhu M, Mizuno H et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228
Erices A, Conget P, Minguell JJ (2000) Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 109:235–242
Liang J, Gu F, Wang H et al (2010) Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE. Nat Rev Rheumatol 6:486–489
Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725
Zhou K, Zhang H, Jin O et al (2008) Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice. Cell Mol Immunol 5:417–424
Sun L, Akiyama K, Zhang H et al (2009) Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells 27:1421–1432
Gu Z, Akiyama K, Ma X et al (2010) Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL/lpr mice. Lupus 19:1502–1514
Sun L, Wang D, Liang J et al (2010) Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum 62:2467–2475
Liang J, Zhang H, Hua B et al (2010) Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis 69:1423–1429
Gupta N, Su X, Popov B et al (2007) Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol 179:1855–1863
Sun J, Han ZB, Liao W et al (2011) Intrapulmonary delivery of human umbilical cord mesenchymal stem cells attenuates acute lung injury by expanding CD4+CD25+ Forkhead Boxp3 (FOXP3)+ regulatory T cells and balancing anti- and pro-inflammatory factors. Cell Physiol Biochem 27:587–596
Kim ES, Chang YS, Choi SJ et al (2011) Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells attenuates Escherichia coli-induced acute lung injury in mice. Respir Res 12:108
Lee JW, Fang X, Gupta N et al (2009) Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Natl Acad Sci USA 106:16357–16362
Carrion F, Nova E, Ruiz C et al (2010) Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic lupus erythematosus patients. Lupus 19:317–322
Sun LY, Zhang HY, Feng XB et al (2007) Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus 16:121–128
Barker TT, Lee PY, Kelly-Scumpia KM et al (2011) Pathogenic role of B cells in the development of diffuse alveolar hemorrhage induced by pristine. Lab Invest 91:1540–1550
Koh H, Nakamae H, Koh KR et al (2010) Serum cytokine profiles at the onset of severe, diffuse alveolar hemorrhage complicating allogeneic hematopoietic stem cell transplantation, treated successfully with pulse intravenous cyclophosphamide. Acta Haematol 124:171–175
Krause DS, Theise ND, Collector MI et al (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cells. Cell 105:369–377
Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 96:10711–10716
Kotton DN, Ma BY, Cardoso WV et al (2001) Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development 128:5181–5188
Lara AR, Schwarz MI (2010) Diffuse alveolar hemorrhage. Chest 137:1164–1171
This work was supported by the National Natural Science Foundation of China (nos. 81072473, 81172847, and 30972736), the Jiangsu Province Natural Science Foundation (no. BK2009034), the Major International (Regional) Joint Research Project (no. 81120108021), and the Jiangsu Province Ke Jiao Xing Wei Program.
Dongyan Shi and Dandan Wang are co-first authors.
About this article
Cite this article
Shi, D., Wang, D., Li, X. et al. Allogeneic transplantation of umbilical cord-derived mesenchymal stem cells for diffuse alveolar hemorrhage in systemic lupus erythematosus. Clin Rheumatol 31, 841–846 (2012). https://doi.org/10.1007/s10067-012-1943-2
- Diffuse alveolar hemorrhage
- Mesenchymal stem cells
- Systemic lupus erythematosus