A rheumatoid arthritis javítása MSC-exo-n keresztül Rh2-vel kombinálva
Bevezetés
In light of a statistics report by World Health Organization (WHO), there are 18 million people suffering from rheumatoid arthritis (RA) worldwide in 2019, where the prevalence of female is 2.5 times that of male. This disorder greatly affects the life quality of patients and even causes disability in severe case. Noteworthily, mesenchymal stem cell-derived exosome (MSCs-exo) in combination with ginsenoside Rh2 has been unveiled to be effective in alleviating RA symptoms, holding a great promise as an adjuvant drug for RA.
About RA
RA represents a chronic autoimmune disease generally occurring in middle age, which is chiefly featured by vascular proliferation, synovium inflammation and the stiffness/swelling/deformation/pain of one or more joints. At present, the treatment of RA relies on corticosteroids, nonsteroidal anti-inflammatory drugs, synthetic disease-modifying anti-rheumatic drugs, and biological agents. Yet, long-term use of these drugs may be accompanied with various adverse effects such as infection, liver damage, gastrointestinal damage, and heart failure.
MSCs vs. MSCs-exo
MSCs, with multiple differentiation potential,tudreduce joint inflammation in RA. Nevertheless, there are potential risks such as immunogenicity, heterogeneity of different batches of cells, tumorigenicity, and ethical issues, limiting the application of MSCs.
MSCs-exo is small extracellular vesicle secreted by MSCs, whose diameter ranges from 30 to 150 nanometers. It can carry biologically active substances such as nucleic acids and small molecules, fulfilling the function of MSCs. Relative to MSCs, MSCs-exo has low immunogenicity and hasno risk of tumor formation and ethical constraints.
MSCs-exo is small extracellular vesicle secreted by MSCs, whose diameter ranges from 30 to 150 nanometers. It can carry biologically active substances such as nucleic acids and small molecules, fulfilling the function of MSCs. Relative to MSCs, MSCs-exo has low immunogenicity and hasno risk of tumor formation and ethical constraints.
Kutatási protokoll
A collagen-induced arthritis (CIA) modelis constructedin rats, followed by the treatment of phosphate-buffered saline or single/combined therapy ofMSCs-exo and ginsenoside Rh2. The rat fences are collected for 16 rRNA amplification sequencing and untargeted metabolomics analysis.
Significant efficacy ofMSCs-exo combinedwith ginsenoside Rh2 in RA
The combined therapy of MSCs-exo and ginsenoside Rh2, to a large extent, amelioratesRA symptoms banCIA model rats, as manifested by the reduction ofjoint swelling as well as significant decline inarthritis score andpaw thickness.
Meanwhile, thehistopathological changes inCIA model rats are apparently improved.Rh2 enhances the ability of MSC-exo to suppress the expression of inflammatory factors in synovium and cartilage of CIA model rats, as evidenced by the downregulationof TNF-α, IL-1β and IL-6valamint azIL-10 in exo+Rh2 group. Besides,bone erosion in the ankle joints of CIA rats is improved, as attested by the obvious increases in BMD and Tb.Th, as well as prominent decreases in BS/BV and Tb.Sp in exo+Rh2 group.
Meanwhile, thehistopathological changes inCIA model rats are apparently improved.Rh2 enhances the ability of MSC-exo to suppress the expression of inflammatory factors in synovium and cartilage of CIA model rats, as evidenced by the downregulationof TNF-α, IL-1β and IL-6valamint azIL-10 in exo+Rh2 group. Besides,bone erosion in the ankle joints of CIA rats is improved, as attested by the obvious increases in BMD and Tb.Th, as well as prominent decreases in BS/BV and Tb.Sp in exo+Rh2 group.
Essential role of gut-joint axis in RA
Gut microbiota and metaboliteshave been deemed to becritical in developing RA. Strikingly,MSCs-exo and Rh2tudsignificantly ameliorate the disturbed gut microbiota in CIAmodellrats. The regulation of Candidatus_Saccharibacteria and Clostridium_XlVb may be the most pivotal. Concretely,Candidatus_Saccharibacteriamodulatesa
metabolic pathway of vitamin digestion and absorption by pantothenic acid and vitamin D3 alterations. As forClostridium_XlVb, it
Szabályozza16(R)-HETE alterations in the arachidonic acid metabolic pathway.
Következtetés
MSCs-exo and Rh2 act synergistically to ameliorate RA by modulating the gut microbiota and metabolites, especially the reshaping of Candidatus_Saccharibacteria and Clostridium_XlVb abundance.
Utalás
Zhou Z, Li Y, Wu S, et al. Host-microbiota interactions in collagen-induced arthritis rats treated with human umbilical cord mesenchymal stem cell exosome and ginsenoside Rh2. Biomed Pharmacother. Published online April 2, 2024. doi:10.1016/j.biopha.2024.116515
BONTAC Ginsenozidok
BONTAC2012 óta foglalkozik koenzimek és természetes termékek nyersanyagainak kutatásával és fejlesztésével, saját tulajdonú gyárakkal, több mint 170 globális szabadalommal, valamint erős kutatás-fejlesztési csapattal. A BONTAC gazdag kutatás-fejlesztési tapasztalattal és fejlett technológiával rendelkezik a bioszintézis területénritka ginsenozidok Rh2/Rg3, with pure raw materials, higher conversion rate and higher content (up to 99%).
Lemondás
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