Walewska Alicja, Tynecka Marlena, Ksiezak Sylwia, Tarasik Agnieszka, Janucik Adrian, Bondarczuk Kinga, Rusak Malgorzata, Dabrowska Milena, Hady Hady Razak, Radziwon Piotr, Sredzinski Dariusz, Reszec-Gielazyn Joanna, Moniuszko Marcin, Eljaszewicz Andrzej
Centre of Regenerative Medicine, Medical University of Bialystok, Ul. Waszyngtona 15B, 15-269, Bialystok, Poland.
Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland.
Stem Cell Res Ther. 2025 Jul 22;16(1):396. doi: 10.1186/s13287-025-04520-1.
Tissue-resident mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), play a crucial role in maintaining tissue homeostasis and repair. However, their function in chronic inflammatory diseases, such as asthma, remains elusive.
Here, we aimed to assess the influence of house dust mite (HDM)-induced asthmatic inflammation on the numbers and function of lung resident (lr)MSCs.
Experimental asthma was induced in female C57BL6/cmdb mice via intranasal HDM administration. LrMSCs were isolated, expanded, and characterized by flow cytometry and differentiation assays. Human adipose tissue-derived (hAD)MSCs were isolated and stimulated with HDM, LPS, or cytokines. Co-culture experiments with peripheral blood mononuclear cells (PBMCs) assessed immunomodulatory potential. Gene expression, cytokine levels, and T-cell proliferation were analyzed.
Here, we showed that asthmatic lung inflammation significantly reduces the number of lrMSCs. More importantly, remaining lrMSCs showed impaired differentiation potential and lacked immunomodulatory functions. Furthermore, we found that exposure of hAD-MSCs to HDM and LPS similarly led to marked inhibition of differentiation potential and suppression of immunosuppressive activities. Notably, this inhibitory effect persisted despite the presence of pro-inflammatory cytokines released by PBMCs in response to LPS and HDM. Furthermore, we showed that inflammatory signaling alone, in the absence of direct LPS and HDM exposure, significantly reduces growth factor-induced adipogenesis and osteogenesis.
Taken together, our findings indicate that asthmatic inflammation not only reduces the number of lrMSCs but also impairs their function, potentially exacerbating disease progression by limiting their immunoregulatory role.
组织驻留间充质干细胞，也称为间充质基质细胞（MSCs），在维持组织稳态和修复中起关键作用。然而，它们在慢性炎症性疾病（如哮喘）中的功能仍不清楚。
在此，我们旨在评估屋尘螨（HDM）诱导的哮喘炎症对肺驻留（lr）MSCs数量和功能的影响。
通过鼻内给予HDM在雌性C57BL6/cmdb小鼠中诱导实验性哮喘。分离、扩增lrMSCs，并通过流式细胞术和分化试验进行表征。分离人脂肪组织来源（hAD）MSCs，并用HDM、LPS或细胞因子刺激。与外周血单核细胞（PBMCs）的共培养实验评估免疫调节潜力。分析基因表达、细胞因子水平和T细胞增殖。
在此，我们表明哮喘性肺炎症显著减少lrMSCs的数量。更重要的是，剩余的lrMSCs显示分化潜能受损且缺乏免疫调节功能。此外，我们发现hAD-MSCs暴露于HDM和LPS同样导致分化潜能的显著抑制和免疫抑制活性的抑制。值得注意的是，尽管存在PBMCs对LPS和HDM反应释放的促炎细胞因子，这种抑制作用仍然存在。此外，我们表明，在没有直接LPS和HDM暴露的情况下，单独的炎症信号显著降低生长因子诱导的脂肪生成和成骨。
综上所述，我们的研究结果表明，哮喘炎症不仅减少lrMSCs的数量，还损害其功能，可能通过限制其免疫调节作用而加剧疾病进展。
