Intratracheal administration of mesenchymal stem cells modulates lung macrophage polarization and exerts anti-asthmatic effects

Abstract

Mesenchymal stem cells (MSCs) possess immunomodulatory properties that have therapeutic potential for the treatment of inflammatory diseases. This study investigates the effects of direct MSC administration on asthmatic airways. Umbilical cord MSCs (ucMSCs) were intratracheally administered to six-week-old female BALB/c mice sensitized and challenged with ovalbumin; airway hyperresponsiveness (AHR), analyses of airway inflammatory cells, lung histology, flow cytometry, and quantitative real-time PCR were performed. Furthermore, ex vivo and in vitro experiments were performed to assess the effects of ucMSC on M2 activation. Intratracheally administered ucMSCs decreased degree of airway resistance and the number of inflammatory cells such as T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), and macrophages in the murine asthma model. Particularly, MHCII and CD86 expression diminished in dendritic cells and alveolar macrophages (AMs) following ucMSC treatment. SiglecF+CD11c+CD11b- AMs show a negative correlation with type II inflammatory cells including Th2 cells, ILC2, and eosinophils in asthmatic mice and were restored following intratracheal ucMSCs treatment. In addition, ucMSCs decreased the macrophage polarization to M2, particularly M2a. The expression levels of markers associated with M2 polarization and Th2 inflammation were also decreased. ucMSC reduced Il-12 and Tnfa expression as well as that of M2 markers such as Cd206 and Retnla ex vivo. Furthermore, the in vitro study using IL-4 treated macrophages confirmed that both direct and indirect MSC treatment significantly reduced the expression of Il-5 and Il-13. In conclusion, ucMSCs appear to suppress type II inflammation by regulating lung macrophages via soluble mediators.

Melatonin-pretreated human umbilical cord mesenchymal stem cells improved endometrium regeneration and fertility recovery through macrophage immunomodulation in rats with intrauterine adhesions

“…On the contrary, M2-type macrophages secrete anti-inflammatory factors, such as IL-4, IL-10, IL-13, TGF- β , and VEGF, to reduce the inflammatory response, which plays a vital role in the normal repair of the tissues [54]. Interestingly, this study found that transplanting melatonin-pretreated HucMSCs allowed the recruitment of more macrophages to the injured tissues and promoted macrophage transformation from the M1 to M2 phenotypes [19, 55]. Moreover, it up-regulated the expression of anti-inflammatory factors and downregulated the expression of pro-inflammatory factors, which provides a better microenvironment for endometrial regeneration [56].…”

Mesenchymal stromal cell-based therapy in lung diseases; from research to clinic

“…Moreover, MSCs can attenuate the pattern of proinflammatory cytokines in the animal model of chronic cigarette smoke exposure [175]. Furthermore, MSC-based therapy can modulate both the expression of miR-193b-5p, leading to the attenuation of sepsisinduced acute lung injury [176], and the polarization of lung macrophages and exerts antiasthmatic effects [177]. Moreover, there is an increase interest toward using MSCs in innovative gene vectors or drugs for cancer treatments [178].…”

3D bioprinted mesenchymal stromal cells in skin wound repair

“…Meanwhile, MSCs also inhibit the proliferation of activated helper T (Th) cells (59). Mo et al found that MSCs suppressed Th2 inflammation by regulating macrophage activation via soluble mediators rather than direct cell-to-cell contact (60). Besides, the extracts of MSCs could suppress Th2 cells and reduce the expression of IL-17 and IFN-γ, which further demonstrate that MSCs inhibit Th2 cells through paracrine factors (61, 62).…”