A Therapeutic Hypothesis for Intrauterine Adhesions: Combining Mesenchymal Stem Cells With Pirfenidone

Document Type : Review article

Authors

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Intrauterine adhesions (IUAs), characterized by fibrous tissue bands within the endometrial cavity, present significant challenges to reproductive health. This condition leads to abnormal menstruation, infertility, and recurrent pregnancy losses. Current treatment modalities primarily focus on endometrial regeneration through hormone therapy and surgical removal of adhesions. However, the success rates of these approaches are unsatisfactory. Stem cell therapies, particularly those involving mesenchymal stem cells (MSCs), have emerged as promising tissue repair and regeneration strategies,  inhibiting inflammation and fibrosis. Nonetheless, while some limitations have been observed in the application of MSCs, their therapeutic effectiveness can be significantly enhanced by combining them with other medications. Furthermore, pirfenidone, an FDA-approved idiopathic pulmonary fibrosis (IPF) drug, has demonstrated anti-fibrotic and anti-inflammatory properties. Consequently, the combined administration of MSCs and pirfenidone can potentially improve therapeutic outcomes by simultaneously targeting the key pathological characteristics of IUAs, namely fibrosis and inflammation. Furthermore, this approach could target other factors involved in IUA pathogenesis. MSCs reduce tissue damage and promote vascularization, while pirfenidone could inhibit fibrotic signaling pathways and improve autophagy defects. This combination offers a comprehensive strategy for treating IUAs by effectively preventing or mitigating these pathogenic mechanisms. Also, this combination could reduce the pirfenidone dosage and prevent potential adverse effects. This article proposes a hypothesis that encourages further investigation of the synergistic effects of MSCs and pirfenidone as potential treatments for IUAs. 

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