The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and rapidly spread worldwide. Since then, scientists have searched to find an effective treatment for coronavirus disease 2019 . In this regard, several antiviral drugs are currently undergoing clinical trial studies to evaluate their safety and efficacy in the treatment of COVID-19. Some of these drugs have been designed based on this fact that SARS-CoV-2 is a positive-sense single-stranded RNA virus and previous studies showed the efficacy of anti-RNA virus, single strand RNA inhibiting antisense RNAs (asRNAs), for silencing virus replication, in vitro. Exosomes can be suggested as a promising candidate to transfer the anti-SARS-CoV-2 asRNAs to human respiratory epithelium. Exosomes are secreted by mesenchymal stem cells (MSCs) and can be loaded by asRNAs of an anti-RNA virus. MSCs-secreted exosomes as a nano-cargo of asRNAs of anti-SARS-CoV-2 have other therapeutic potentials such as immunomodulatory effects of their cytokine contents, affinity to respiratory epithelial attachment, anti-fibrotic activity in lung, non-toxicity for normal cells, and not triggering an immune response. Moreover, inhalation of anti-SARS-CoV-2 asRNAs may stop SARS-CoV-2 replication. Producing specific anti-SARS-CoV-2 asRNAs by targeting the genome of virus and their delivery by MSCs exosomes are suggested and discussed. This approach will potentially shed light on gene therapy of the other human lung diseases via inhalational delivery using exosomes in future.

Background One of the main cause of male infertility is non-obstructive azoospermia, which is not manageable medically. The first aim of the current research was to show the effect of extracellular vesicle-contained conditioned media (CM) instead of mesenchymal stromal/stem cells (MSCs) for treatment of non-obstructive azoospermia. In the next step, we aimed to study the differentiation potential of MSCs into spermatocytes after injection of MSCs in mice seminiferous tubules. This study has provided an applied treatment for busulfan-induced azoospermia using adipose tissue-derived (AT-MSCs) and bone marrow-derived MSCs (BM-MSCs) and bone marrow CM (BMCM) in animal models. Methods Thirty male adult Balb/C mice (30±5 g) and two female eGFP+/+Balb/C mice (30±5 g) were used to design experimental groups and to culture stem cells, respectively. Then, six groups including intact control, azoospermia, AT-MSC therapy, BM-MSC therapy, BMCM therapy, and spontaneous healing groups were considered. All groups except intact control were induced azoospermia by injecting two doses of busulfan (10 mg/kg) with 21 days’ interval. Testes of all mice were removed and studied through histomorphometry and flow cytometry analysis 60 days after treatment. Results Histomorphometry and flow cytometry evaluation of testes showed normal morphology of most of the seminiferous tubules of therapy groups as well as successful recovery of spermatogenesis, but spermatogenesis was not observed in the azoospermia group. It is worth notable that the results of the BM-MSC therapy group were more favorable than other therapy groups. Conclusions AT-MSC, BM-MSC and BMCM can be strongly suggested as candidates in the therapy of azoospermia.

One of the main cause of male infertility is non-obstructive azoospermia, which is not manageable medically. The first aim of the current research was to show the effect of extracellular vesicle-contained conditioned media (CM) instead of mesenchymal stromal/stem cells (MSCs) for treatment of non-obstructive azoospermia. In the next step, we aimed to study the differentiation potential of MSCs into spermatocytes after injection of MSCs in mice seminiferous tubules. This study has provided an applied treatment for busulfan-induced azoospermia using adipose tissue-derived (AT-MSCs) and bone marrow-derived MSCs (BM-MSCs) and bone marrow CM (BMCM) in animal models. In this regard, 30 male adult Balb/C mice (30±5g) and two female eGFP+/+ Balb/C mice (30±5g) were used to design experimental groups and to culture stem cells, respectively. Then, six groups including intact control, azoospermia, AT-MSC therapy, BM-MSC therapy, BMCM therapy, and spontaneous healing groups were considered. All groups except intact control were induced azoospermia by injecting two doses of busulfan (10 mg/kg) with 21 days’ interval. Testes of all mice were removed and studied through histomorphometry and flow cytometry analysis 60 days after treatment. Histomorphometry and flow cytometry evaluation of testes showed normal morphology of most of the seminiferous tubules of therapy groups as well as successful recovery of spermatogenesis, but spermatogenesis was not observed in the azoospermia group. It is worth notable that the results of the BM-MSC therapy group were more favorable than other therapy groups. Consequently, AT-MSC, BM-MSC and BMCM can be strongly suggested as candidates in the therapy of azoospermia.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 is rapidly spreading worldwide. Scientists are searching to find an effective treatment for coronavirus disease 2019 (COVID-19). Several antiviral drugs are currently undergoing clinical trial studies to evaluate their safety and efficacy in the treatment of COVID-19. SARS-CoV-2 is a positive-sense single-stranded RNA virus. Previous studies showed the efficacy of anti-RNA virus, single strand RNA inhibiting antisense RNAs (asRNAs), on silencing of virus replication, in vitro. To transfer the anti-SARS-CoV-2 asRNAs to human respiratory epithelium, exosomes can be suggested as a promising candidate. Mesenchymal stem cells (MSCs) secret exosomes and they can be loaded by anti-RNA virus asRNAs. MSCs-secreted exosomes as a nano-cargo of anti-SARS-CoV-2 asRNAs have other therapeutic potentials such as immunomodulatory effects of their cytokine contents, affinity to respiratory epithelial attachment, anti-fibrotic activity in lung, non-toxicity for normal cells, and do not trigger an immune response. Inhalation of anti-SARS-CoV-2 asRNAs may stop SARS-CoV-2 replication. Producing a specific anti-SARS-CoV-2 asRNAs by targeting the genome of virus and their delivery by MSCs exosomes is suggested and discussed. This approach potentially sheds light on gene therapy of the other human lung diseases via inhalational delivery using exosomes in future.