December 7, 2022

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Three Application Studies of Stem Cell Transplantation in Lupus Nephritis

Three Application Studies of Stem Cell Transplantation in Lupus Nephritis



Clinical case: Three Application Studies of Stem Cell Transplantation in Lupus Nephritis

Overview

1. Lupus nephritis (LN) is the most common and most serious clinical manifestation of SLE.

2. It is caused by the deposition of autoantigen-antibody complexes in the glomerulus, renal interstitium, and renal tubules. The pathology is diverse and changeable.

3. The clinical changes are diverse, including hematuria and/or proteinuria, nephritis syndrome, nephrotic syndrome, acute or chronic renal failure.

4. After active treatment, the short-term effect is good, and the long-term prognosis is poor.

Three Application Studies of Stem Cell Transplantation in Lupus Nephritis

Pathogenesis

1. For immune complex nephritis.

2. Most of them are circulating immune complexes, and a few are in situ immune complex deposition.

3. Antiphospholipid antibodies, vascular endothelial cells, platelet dysfunction, thrombotic microangiopathy, kidney damage.

4. Hypertension, abnormal blood coagulation, and aggravate kidney damage.

In terms of treatment, although the combined application of immunosuppressants and glucocorticoids has achieved good clinical effects, the morbidity and mortality of some refractory patients have not been reduced.

Stem cells have clinical value for lupus nephritis

In recent years, research on stem cell therapy has developed rapidly, and mesenchymal stem cells have a wide range of sources. It has the advantages of immune regulation and other advantages, which has become a research hotspot in the treatment of refractory LN.

The mechanism of MSCs in the treatment of LN

Regulation of MScs on T lymphocytes: T lymphocytes play a major role in the pathogenesis of LN.

Regulation of MsCs on B lymphocytes: Compared with non-LN patients, LN patients have an increased number of B lymphocytes. The main ways that B lymphocytes participate in the pathogenesis of LN are as follows: (1) produce many autoantibodies; (2) secrete a variety of pro-inflammatory cytokines with autocrine and paracrine effects.

The regulation of MSCs on dendritic cells (DCs): In LN, DCs can infiltrate the kidney, have the functions of presenting antigens and tissue amplifying the tertiary lymphoid tissue structure of inflammation, and have a unique ability to stimulate the activation of T cells.

Possible mechanism of MSCs regulating other factors: MSCs regulating IL-10: Many cells such as 7n12 cells, Th1 cells and Treg cells can produce IL-10. IL-10 plays a key role in the stability of cellular and humoral immunity It has immunostimulatory and inhibitory effects.

Basic research on the treatment of LN with MSCs

Collins et al. used MSCs derived from human UC, human BM, and lupus patient bone marrow (LBM), and successively transplanted the tail vein into MRL/lpr mice. Experimental results show that transplantation of human UC and BM-derived stem cells in MRL/lpr mice can reduce proteinuria, reduce inflammation markers, and improve the pathological structure of the kidney.

Thiel et al. used human embryonic stem cells (hEsc)-Mscs to be transplanted into NzBxNzw F1 mice, and found that mice proteinuria and blood creatinine decrease were statistically significant, and they protected the kidneys, reduced kidney damage, and reduced renal lymphocyte infiltration.

Clinical study of Mscs in the treatment of LN

Tang Bangli et al. used a randomized, double-blind method to observe the clinical manifestations of 12 LN patients after receiving human uc-Mscs treatment. Follow-up for 6 months, the SLEDAI score of the uc-Mscs group decreased, clinical symptoms such as fever, butterfly erythema, arthralgia, and lower extremity edema were relieved, proteinuria content decreased, IL-10, INF-1, IL-4 inflammatory factor expression The level decreased, which was statistically significant with the control group.

Hua Wen et al. observed the condition of 3 patients with active LN after receiving BM-MSCs treatment. During the 9-month follow-up, 3 patients had renal function indexes such as proteinuria, hematuria, white blood cell urine, blood creatinine, and glomerular filtration rate. All were improved; the sLEDAI scores of 3 patients were significantly improved; no adverse events occurred.

Mscs combined with hematopoietic stem cells has a good clinical effect in the treatment of refractory LN.

A 25-year-old young woman received autologous hematopoietic stem cell and Mscs transplantation when the combination of hormones and immunosuppressants did not work. The two co-transplantation showed a good therapeutic effect. After 36 months of follow-up, proteinuria, anti-ds-DNA antibodies, complement, renal function, and SLEDAI scores were maintained within a good range.


Summary and outlook

Basic experiments and clinical trials have shown that Msc has a significant effect on LN, which can improve kidney function, reduce proteinuria, reduce autoantibody concentration, and improve survival.

Three Application Studies of Stem Cell Transplantation in Lupus Nephritis

(sourceinternet, reference only)


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