Abstract
Bone marrow mesenchymal stem cells (BMSCs) have been considered to be an important regulator for immune function. We aim to prove the function improvement of aging spleen and thymus induced by BMSCs and unfold the specific mechanisms. Aging animal model was established using D-galactose. The morphological changes of spleen and thymus tissues were observed using hematoxylin-eosin staining and transmission electron microscopy. Key cytokines in the serum were measured with enzyme linked immunosorbent assay. Protein and mRNA levels of P16, P21, and PCNA were detected using western blotting and RT-qPCR. Special markers of BMSCs were identified using flow cytometry, and successful induction of BMSCs to steatoblast and osteoblasts was observed. Compared to aging model, BMSCs significantly increased the spleen and thymus index, improved the histological changes of spleen and thymus tissues. A remarkable increase of ratio between CD4+T cells and CD8+T cells, level of IL-2 was achieved by BMSCs. However, BMSCs markedly inhibited the content of IL-10, TNF-a, P16, and P21 but promoted PCNA. Significant inhibition of oxidative stress by BMSCs was also observed. We demonstrated that BMSCs significantly improved the tissue damage of aging spleen and thymus, BMSCs may improve aging organs through influencing cytokines, oxidative stress, and P21/PCNA.
Highlights
Dysfunction of immune system is an important symbol for aging body
We demonstrated that Bone marrow mesenchymal stem cells (BMSCs) significantly improved the tissue damage of aging spleen and thymus, BMSCs may improve aging organs through influencing cytokines, oxidative stress, and P21/PCNA
The biomarkers of BMSCs were measured by flow cytometry. 99.9% CD29 and 97.8% CD44 positive cells, 99.3% CD34 and 99.1% CD45 negative cells were observed suggesting that the cells we isolated should be BMSCs (Figure 1E)
Summary
Dysfunction of immune system is an important symbol for aging body. Thymus is a central lymphoid organ responsible for production of naive T cells, which plays a vital role in mediating both cellular and humoral immunity [1]. Chronic involution of thymus gland is thought to be one of the major contributing factors to immune function loss with increasing age [2]. Spleen is commonly involved in the regulation of humoral immunity [3]. Both thymus and spleen have been considered to be closely linked with body aging. BMSCs can be used as seed cells for cell therapy because of homing to damaged tissues, repairing tissues and regulating immune system [5, 6]
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