Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL/lpr mice

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which, despite the advances in immunosuppressive medical therapies, remains potentially fatal in some patients, especially in treatment-refractory patients. This study found that transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) has the same therapeutic effect as transplantation of bone marrow mesenchymal stem cells (BM-MSCs), which has been reported to be efficient in treating SLE-related symptoms in MRL/lpr mice. Multi-treatment (at the 18th, 19th, and 20th weeks of age) of 1 × 10(6) UC-MSCs was able to decrease the levels of 24-h proteinuria, serum creatinine, and anti-double-stranded DNA (dsDNA) antibody, and the extent of renal injury such as crescent formation in MRL/lpr mice. A lower, but still significant, reduction in these parameters was also observed in mice receiving a single dose of UC-MSCs (at the 18th week). UC-MSCs treatment also inhibited expression of monocyte chemotactic protein-1 (MCP-1) and high-mobility group box 1 (HMGB-1) expression in a similar fashion. UC-MSCs labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) were found in the lungs and kidneys 1 week post infusion. In addition, after 11 weeks post UC-MSCs infusion, human cells were found in kidney of UC-MSCs-treated mice. These findings indicated that UC-MSCs transplantation might be a potentially promising approach in the treatment of lupus nephritis, possibly by inhibiting MCP-1 and HMGB-1 production.

Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjögren syndrome

“…20,41,42 Compared with BMMSCs, UCMSCs have significant advantages as a cellular source for MSC-mediated therapy: (1) collection from the umbilical cord is easy and noninvasive for the donor 43 ; (2) umbilical cords can be stored in advance, whereas bone marrows specimens have to be collected from the donor immediately before infusion; (3) MSCs from the umbilical cord are more primary than MSCs isolated from some other tissue sources 44 ; and (4) UCMSCs have greater proliferative potential and possess therapeutic effects in experimental and human autoimmune diseases. 21,45 Clinically, treatment for hypofunction of salivary gland in primary SS remained a challenge, long-term use of sialagogue can only alleviate xerostomia and usually be with adverse effects. Here we showed that treatment of UCMSCs in 24 patients with primary SS resulted in considerable improvements in disease activity and organ function, demonstrating UCMSCs as a reliable cellular source of MSCs and their infusion as a novel therapeutic approach for SS.…”

Mesenchymal Stem Cell Therapy for rheumatic diseases

“…Youd et al (5) concluded that , the use of allogenic bone-marrow-derived MSCs in mice with SLE worsened the disease activity, increased the level of autoantibody and proteinuria. In contrast, in Gu et al (6) and Zhou et al (7), after the use of UC-derived MSC and bone-marrow-derived MSC, respectively, SLE mouse models had clinical improvements, together with reduction in anti-double-stranded DNA (anti-ds DNA), proteinuria and creatinine levels.…”

Human embryonic mesenchymal stem cells alleviate pathologic changes of MRL/Lpr mice by regulating Th7 cell differentiation

“…26 In the autoimmune environment, MSC can improve the dysfunction of the T-cell subset. 27 Studies concerning MSC treatment of SLE patients 9,28 and lupus animal models 29,30 showed that either autogenic, xenogenic, or umbilical BMSC could inhibit Th17 differentiation by increasing the number of Treg cells, which is consistent with the finding of the present study that hMSC therapy could down-regulate the Th17 cell ratio in the spleen of MLR/Lpr mice and the serum IL17 concentration, suggesting that the therapeutic efficacy of hMSC is associated with their inhibitory effect on Th17 cell differentiation and decreased secretion of IL-17. The mechanism of SLE treatment with MSC involves multiple aspects, including direct differentiation of MSC into healthy tissues and organs, immunomodulation, and paracrine and endocrine effects, of which immunomodulation is an important factor, though the exact mechanism and outcome remain indefinite.…”