• Exosomes as tools for personalized miRNA delivery in infertility treatment
  • Kimia Sadat Nazemi,1 Saba Safdarpour,2,*
    1. Department of Cellular and Molecular Biology, TeMS.C., Islamic Azad University, Tehran, Iran
    2. Department of Cellular and Molecular Biology, TeMS.C., Islamic Azad University, Tehran, Iran


  • Introduction: Infertility is an important health issue for about 15% of couples around the world. Despite the progress of international technologies such as the training ARTs- IVFs; recurrent implantation failure, poor pregnancy outcomes, and unexplained infertility continuously stress the importance of innovative and individualized treatments. The most recent works highlighted the development of microRNAs as innovative and very important therapeutic- biologically active regulator of gene expression. microRNAs become important in the development of infertility from dysfunctional spermatogenesis and oogenesis through implantation and failure of endometrial receptivity. The use of naked microRNAs in therapy confronted problems of rapid degradation, loss of fat and targeted reproductive tissues. Exosomes offer the most elegant solution. As biologically active regulators of gene expression, they function as natural nanocarriers, stably and precisely transporting their microRNAs and other cargo to target recipient cells undetected and without a strong immune response. This review attempts to highlight the promise of engineered exosomes to deliver therapeutic- recipient targeted microRNAs for individualized therapy and treatment of infertility to address the mechanisms active- targeted delivery and the barrier of clinical usage.
  • Methods: To create this review, we conducted searches in top tier databases such as PubMed, ScienceDirect, and Scopus. we combined search terms like “Exosome miRNA delivery infertility,” “Engineered exosomes personalized medicine,” “miRNA reproductive system,” “Exosome targeting,” and “MSC Exosomes.” we included review articles from 2018 and selected innovative studies involving exosome engineering and personalized medicine in reproductive biology to capture recent advances in the field.
  • Results: Exosomes, miRNAs, and Personalized Biomarkers Research shows that the miRNAs found within biofluid exosomes (e.g., follicular fluids and seminal plasma) offer a non-invasive means of determining the quality of oocytes, sperm, and the endometrium receptivity. For example, malfunction of specific apoptosis and inflammation regulatory miRNAs is associated with implantation failures and POI (premature ovarian insufficiency). This is the essence of that personalized approach, where the diagnostic first defines the disrupted miRNA profile, and personalized therapy entails the designing of corresponding miRNAs. Exosome Engineering for Targeted miRNA Delivery Exosomes which are derived from Mesenchymal Stem Cells (MSC-Exosomes) are considered a preferred source due to the regenerative and anti-inflammatory properties. However, in order to deliver therapeutic miRNAs, exosomes have to be engineered. For efficient loading of particular miRNAs (chosen based on the patient profile, which is unique for every single person) customized biological approaches like electroporation and lipid-based methods are used. However, the most important thing is that exosomes can be surface modified with specific peptides or ligands to hit particular reproductive cells (i.e., ovarian granulosa cells or testicular Sertoli cells). Repair at the damaged site becomes highly effective with therapeutic concentration. Challenges and Prospects for Clinical Translation Exosomes hold great potential for clinical application, yet there are obstacles that must be addressed. Among the most significant are the large-scale production, the optimization of the consistency and quality of the exosomal miRNA content, as well as the regulatory and safety requirements. With continued improvements in isolation and bioengineering technologies, however, we expect engineered exosomes to be highly targeted, safe, personalized engineered exosomes that will revolutionize the management of complicated infertility in the foreseeable future.
  • Conclusion: Exosomes have the potential to be a breakthrough new therapy for the limitations of the current medicine for infertility. The ability to personalize the therapeutic delivery of miRNAs through bioengineering and the use exosomes as a biological carrier open new innovative ways for improving success rates for patients suffering from infertility. The next step for research in this area is to focus on standardizing production and carrying out thorough clinical research. The aim of this research would be to make this advanced therapy accessible to clinicians.
  • Keywords: microRNA Infertility Personalized medicine Reproductive biology