Chronic asthmatic condition modulated the onset of aging in bone marrow mesenchymal stem cells

Abstract

The emergence of an inflammatory condition such as asthma could affect the therapeutic potential of stem cells. Synopsis of previous documents yielded controversial outcomes, leading to a limitation of stem cell‐based therapy in the clinical setting. This study aimed to assess the impact of asthmatic serum on the MSCs aging and dynamic growth in vitro. Rats were divided into control and asthmatic groups randomly. The asthmatic change was induced using OVA sensitization. The asthmatic structural changes are monitored by conventional Haematoxylin‐Eosin staining. Thereafter, blood samples were taken and sera provided from each group. In this study, primary bone marrow mesenchymal stem cells were cultured in culture medium supplemented with normal and asthmatic serum for 7 days. The MSCs viability was examined using the MTT assay. The expression of the aging‐related gene (β‐galactosidase), and stemness‐related markers such as Sox2, Kfl‐4 and p16INK4a were analysed by real‐time PCR assay. Histological examination revealed chronic inflammatory remodelling which is identical to asthmatic changes. MTT assay showed a reduction of mesenchymal stem cell viability compared to the control group (P < .05). Real‐time PCR analysis revealed a down‐regulation of stemness‐related markers Sox2, Kfl‐4 and p16INK4a coincided with aging changes (β‐galactosidase) compared to the control group (P < .05). These data show the detrimental effect of asthmatic condition on bone marrow regenerative potential by accelerating early‐stage aging in different stem cells and further progenitor cell depletion. Significance of the study In such inflammatory conditions as asthma, the therapeutic potential of stem cells may be altered. We demonstrate that serum from asthmatic rats had the potential to reduce the viability of mesenchymal stem cells in vitro. Furthermore, we observed that the expression of the aging‐related gene known β‐galactosidase was statistically increased in cells co‐cultured with asthmatic serum. At the same time, expression of stemness‐related markers Sox2, Kfl‐4 and p16INK4a down‐regulated. These results support the damaging effect of asthmatic condition on bone marrow regenerative ability by inducing early‐stage aging in stem cells and additional progenitor cell reduction.

Type 2 diabetes mellitus stimulated pulmonary vascular inflammation and exosome biogenesis in rats

“…For example, under hypoglycemic conditions cardiomyocytes release high levels of Exo enriched with specific cargo 38,39 . In a study conducted by Almohammai et al, activated Exo biogenesis and secretion were shown in asthmatic rat lungs and BAL 40 . They concluded that increased Exo can be associated with inflammatory responses.…”

“…38,39 In a study conducted by Almohammai et al, activated Exo biogenesis and secretion were shown in asthmatic rat lungs and BAL. 40 They concluded that increased Exo can be associated with inflammatory responses. More recently, our team found that the inflammatory responses were increased after immune cell recruitment into the lung tissues in a rat model of T2DM.…”

Exosomes for gene therapy effectively inhibit the endothelial-mesenchymal transition in mouse aortic endothelial cells

“…Dynamic histomorphometry showed that compared with normal bone, ectopic ossified bone had higher metabolic activity, increased bone deposition rate, wider bone suture, and larger number of osteoblasts [ 30 ]. The fate of progenitor cells such as mesenchymal stem cells can be affected by stimulation from microenvironment [ 31 , 32 ], and it has been proved that progenitor cells, inflammation niches and disorder of signaling pathway promote the formation of HO. Based on previous studies of HO related molecular mechanism and signaling pathway, we studied the targeted gene therapy method that may be used for the treatment of HO.…”

Mesenchymal Stem/Stromal Cells in Asthma Therapy: Mechanisms and Strategies for Enhancement

“…Transplanted MSCs suffer from microenvironmental changes involving hypoxia (21% O 2 in vitro culture, 2%–8% oxygen in the body) 29 , nutrient deficiency 109 , increased levels of oxidative stress 23 , and recruitment of immune cells post-transplantation 110 , all of which hamper the therapeutic potential of MSCs 25 , 111 , 112 . Culturing MSCs in media with hypoxia, inflammatory cytokines, or asthmatic serum to mimic the in vivo microenvironment can improve the survival or therapeutic potential of MSCs.…”

“…However, MSC-based strategies for asthma treatment are challenging. For example, limited in vitro amplification, gradual loss of stemness, and harsh microenvironments impair the therapeutic potential of transplanted MSCs and impede their prospects for clinical application 22 – 25 . Over the years, various strategies have been used to improve therapeutic effects by enhancing the properties of MSCs or the local microenvironment to help MSCs survive 26 – 30 .…”