OVEREXPRESSION OF HEME OXYGENASE-1 IN MESENCHYMAL STROMAL CELLS: A NOVEL THERAPEUTIC APPROACH FOR ALLERGIC RHINITIS

Xinyan Cui¹, Ruoxi-Chen¹, Keqing-Zhao², Qingzhao Zhang^{1, 2, *} 

¹Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China - ²Department of Otolaryngology-Head and Neck Surgery, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, China

Objective: Allergic rhinitis (AR) is an atopic disorder of the nose induced after allergen exposure through IgE-mediated inflammation. Although AR has become a significant global public health concern and led to heavy financial burden, the curative effect of the available treatments is not completely satisfactory. Mesenchymal stem cells (MSCs) therapy has been considered as a promisingly alternative approach for allergic diseases with their immunomodulatory effect. However, many issues remain to be conquered, for example, MSCs would lose their phenotypes after several passages in vitro, and their immunomodulatory effect still needs to be improved. Heme oxygenase-1 (HO-1), the rate-limiting enzyme for heme degradation, is noticed by its ability to improve the anti-allergic effect of MSCs in vitro. Nonetheless, few study has been conducted to test this effect in vivo.

Methodology: Here, we modified MSCs therapy strategy by transduction of SV-40 into MSCs to make them immortalized in vitro (iMSCs) and further transduced HO-1 gene into iMSCs (HO-1 iMSCs). Then we tested the immunomodulatory effect of HO-1 iMSCs in the mouse model of AR. Our results demonstrate that the modified strategy is technically feasible, and HO-1 iMSCs has stronger anti-allergic effect accompanied with higher generation of CD25⁺Foxp3⁺ regulatory T cells than their controls in vivo. 

Conclusion: These findings suggest that HO-1 iMSCs may become a novel therapeutic strategy for future clinical use to treat AR patients.