Low-Molecular-Weight Heparin Enhanced Therapeutic Effects of Human Adipose-Derived Stem Cell Administration in a Mouse Model of Lupus Nephritis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Jan 31

PMID 35095868

Authors

Shogo Matsuda

Takuya Kotani

Takashi Saito

Takayasu Suzuka

Tatsuhiko Mori

Tohru Takeuchi

Affiliations

Soon will be listed here.

Abstract

Background: Lupus nephritis is a life-threatening complication in systemic lupus erythematosus (SLE), but the efficiency of current therapies involving corticosteroids, immunosuppressants, and biological agents is limited. Adipose-derived mesenchymal stem cells (ASCs) are gaining attention as a novel treatment for inflammation in SLE. Low-molecular-weight heparin (LMWH) exhibits multiple functions including anti-inflammatory, anti-fibrotic, and cell function-promoting effects. LMWH stimulation is expected to increase the therapeutic effect of ASCs by promoting cellular functions. In this study, we investigated the effects of LMWH on ASC functions and the therapeutic effect of LMWH-activated human-ASCs (hep-hASCs) in an SLE mouse model.

Methods: The cellular functions of human-derived ASCs stimulated with different LMWH concentrations were observed, and the optimum LMWH dose was selected. The mice were assigned to control, human-ASC, and hep-hASC groups; treatments were performed on week 20. Twenty-six week-old mice were sacrificed, and urine protein score, serum blood urea nitrogen, creatinine (Cr), anti-ds DNA IgG antibody, and serum IL-6 levels were analyzed in each group. Mice kidneys were evaluated histological examination, immunohistochemical staining, and gene expression levels.

Results: LMWH significantly promoted ASC migration and proliferation and hepatocyte growth factor production and upregulated immunomodulatory factors . Hep-hASC administration resulted in significant disease activity improvement including proteinuria, serum Cr and IL-6 levels, anti-ds DNA IgG antibody, glomerulonephritis, and immune complex in mice. Inflammation and fibrosis in kidneys was significantly suppressed in the hep-hASC group; the gene expression levels of TNF-alpha, TIMP-2, and MMP-2 was significantly downregulated in the hep-hASC group compared with the control group.

Conclusions: Hep-hASC exhibited higher anti-inflammatory and anti-fibrotic effects than hASCs and may be a candidate tool for SLE treatment in future.

Citing Articles

Mesenchymal Stromal Cell-Based Therapy: A Promising Approach for Autoimmune Diseases.

Li L, He Y, Zhao J, Yin H, Feng X, Fan X Clin Rev Allergy Immunol. 2025; 68(1):21.

PMID: 39982546 DOI: 10.1007/s12016-025-09030-9.

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