Page 4 - Mesenchymal Stem cells, Exosomes and vitamins in the fight aginst COVID
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Chemistry and Physics of Lipids 234 (2021) 105009
         L. Rezakhani et al.
         RNAs that regulate the mRNA translation of target genes by interaction   alleviate ARDS is well known (Ghorbani et al., 2017).
         with 3’ untranslated region of relating mRNA (Abdollahi et al., 2019).   This technique can be used as an effective therapy for the delivery of
         Since  viral  protein  synthesis  occurs  in  the  host  cell,  this  regulatory   different  synthetic  and  biological  molecules  in  cellular  therapy  of
         function of miRNAs can be used against viral diseases. Using miRNAs in   various diseases. Indeed, these cells can be considered as potent drug
         this purpose requires perfect or near-perfect matches with the mRNA of   stores releasing biologically active substances. Furthermore in compar-
         the viral genome (gRNA) or parts of its genome that is protein-coding.   ison with other treatments such as monoclonal antibody therapy, the
         This  binding,  cause  cleavage  and  degradation  of  the  target  gene   costs  of  MSC-secretome  seem  probably  lower  which  is  important  in
         (Yekta et al., 2004). Therefore, in order to minimize the side effects, it is   treating  a  pandemic  (Caplan,  2017).  Despite  the  potential  of
         important to select a sequence of miRNAs that specifically bind to the   MSC-derived exosomes for treatment of SARS-CoV-2, the use of exo-
         virus  genome.  Complementary  sequences  to  the  human  genome  can   somes  for  any  purpose  in  SARS-CoV-2,  including  but  not  limited  to
         including  non-specific  gene  silencing  (Singh  et  al.,  2011).  There  are   reducing  cytokine  storm,  exerting  regenerative  effects  or  delivering
         several powerful programs to identify and predict gene targets of miR-  drugs  are  currently  pending  the  generation  of  appropriate
         NAs, such as MirTarget, MiRanda, TargetScan and, PicTar II (Sethupathy   manufacturing  and  quality  control  provisions  (Borger  et  al.,  2020).
         et al., 2006). Ivashchenko and colleagues (Ivashchenko et al., 2020),   Current  clinical  trials  highlight  the  potential  benefits  of  stem  cell
         decided  to  identify  human  miRNAs  that  affect  the  expression  of   secretome therapies for COVID-19 patients. However, further studies are
         SARS-CoV-2  coronavirus  genomes.  Their  goal  was  to  design  a  set  of   therefore  important  to  clarify  the  safety  and  effectiveness  of  these
         miRNAs  that  would  specifically  bind  to  the  coronavirus  genome  to   therapies and their long-term outcomes.
         destroy it, without any side effects on human gene expression which
         may have the potential to be used as a new approach in coronavirus
                                                              Declaration of Competing Interest
         treatment.  Using  MirTarget,  they  identified  miR-5197-3p  out  of  the
         2565 miRNAs that had the greatest potential to interaction with the
                                                                 The authors report no declarations of interest.
         gRNA of SARS-CoV-2, without having target genes among the 17,508
         human coding genes.
                                                              Acknowledgments
           A possible explanation for the fact that SARS-CoV-2 infection is less
         frequently observed in children aged less than 15 years compared to
                                                                 The  authors  acknowledge  the  Cellular  and  Molecular  Research
         adults over 60 years is that the expression of piwi-interacting RNA (pi-
                                                              Center of Kurdistan University of Medical Sciences for supporting our
         RNA)  and  miRNA  is  Age-Dependent  phenomena,  in  fact  pi-RNA
         expression  is  decreased  with  age,  while  miRNA  expression  is   team.  This  research  did  not  receive  any  specific  grant  from  funding
                                                              agencies in the public, commercial, or not-for-profit sectors.
         increased.  It seems  that during  ontogenesis the  expression  of  one or
         more pi-RNAs that can bind to the viral gRNA decreases. Likewise, the
         concentration of miRNAs capable of binding to the gRNA and expressed   References
         in the early stages of ontogenesis may decrease, and the virus begins to
                                                              Abdollahi, A., Rahmati, S., Ghaderi, B., Sigari, N., Nikkhoo, B., Sharifi, K., et al., 2019.
         multiply (Zhou et al., 2018; Lee et al., 2020).,
                                                                 A combined panel of circulating microRNA as a diagnostic tool for detection of the
                                                                 non-small cell lung cancer. QJM Int. J. Med. 112 (10), 779–785.
         5. Exosomes for drug delivery                        Abraham, A., Krasnodembskaya, A., 2020. Mesenchymal stem cell-derived extracellular
                                                                 vesicles for the treatment of acute respiratory distress syndrome. Stem Cells Transl.
                                                                 Med. 9 (1), 28–38.
           In long-distance cell to cell communication, exosomes are of great   Andaloussi, S.E., M¨ ager, I., Breakefield, X.O., Wood, M.J., 2013. Extracellular vesicles:
         importance  because  they  can  enter  the  circulation  and  pass  through   biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov. 12 (5),
                                                                 347–357.
         additional biological barriers. More recent evidence indicates that they
                                                              Asadi, S., Bouvier, N., Wexler, A.S., Ristenpart, W.D., 2020. The Coronavirus Pandemic
         can carry rich cargo between cells. Due to the specific structure of the   and Aerosols: Does COVID-19 Transmit Via Expiratory Particles? Taylor & Francis.
         exosomes various drugs can be inserted into them so they can be used in   Bari, E., Ferrarotti, I., Torre, M.L., Corsico, A.G., Perteghella, S., 2019a. Mesenchymal
         a variety of diseases as drug delivery systems (Vader et al., 2016). In   stem/stromal cell secretome for lung regeneration: the long way through
                                                                 “pharmaceuticalization” for the best formulation. J. Control. Release 309, 11–24.
         addition, in personalized medicine, exosomes can be separated from the   Bari, E., Ferrarotti, I., Torre, M.L., Corsico, A.G., Perteghella, S., 2019b. Mesenchymal
         patient’s plasma, then filled with the exogenous drug of interest, and   stem/stromal cell secretome for lung regeneration: the long way through
         finally given back to the same patient (Lamichhane et al., 2015). The   “pharmaceuticalization” for the best formulation. J. Control. Release.
                                                              Bari, E., Ferrarotti, I., Saracino, L., Perteghella, S., Torre, M.L., Corsico, A.G., 2020.
         immunomodulatory  cargo  of  MSCs  exosomes  combined  with  the   Mesenchymal stromal cell secretome for severe COVID-19 infections: premises for
         anti-viral drugs makes them a novel intervention tool for the treatment   the therapeutic use. Cells 9 (4), 924.
         of the disease (Gupta et al., 2020). Remdesivir antiviral drug, which is   Borger, V., Weiss, D.J., Anderson, J.D., Borr` as, F.E., Bussolati, B., Carter, D.R., et al.,
                                                                 2020. International Society for Extracellular Vesicles and International Society for
         prescribed  for  the  treatment  of  patients  with  Covid-19  (Zhou  et  al.,
                                                                 Cell and Gene Therapy Statement on Extracellular Vesicles From Mesenchymal
         2020; Grein et al., 2020), can be load in to the exosome. However, in the   Stromal Cells and Other Cells: Considerations for Potential Therapeutic Agents to
         case of COVID-19, more scrutiny is essential to have a full understanding   Suppress Coronavirus disease-19.
                                                              Caplan, A.I., 2017. Mesenchymal stem cells: time to change the name! Stem Cells Transl.
         of their safety, specificity, proficiency, and delivery mechanisms of an-
                                                                 Med. 6 (6), 1445–1451.
         tiretroviral drugs to target tissues.                Crivelli, B., Chlapanidas, T., Perteghella, S., Lucarelli, E., Pascucci, L., Brini, A.T., et al.,
                                                                 2017. Mesenchymal stem/stromal cell extracellular vesicles: from active principle to
                                                                 next generation drug delivery system. J. Control. Release 262, 104–117.
         6. Conclusion
                                                              Di Rocco, G., Baldari, S., Toietta, G., 2016. Towards therapeutic delivery of extracellular
                                                                 vesicles: strategies for in vivo tracking and biodistribution analysis. Stem Cells Int.
           To overcome the pandemic of COVID-19, we need to develop a multi-   2016.
                                                              Farooqi, A.A., Desai, N.N., Qureshi, M.Z., Librelotto, D.R.N., Gasparri, M.L., Bishayee, A.,
         directional strategy to minimize its prevalence. In this infection, severe
                                                                 et al., 2018. Exosome biogenesis, bioactivities and functions as new delivery systems
         cytokine storm is the main contributor to organ damage, MSCs not only   of natural compounds. Biotechnol. Adv. 36 (1), 328–334.
         suppress the cytokine storm but also facilitate endogenous regenerative   Ferreira, J.R., Teixeira, G.Q., Santos, S.G., Barbosa, M.A., Almeida-Porada, G.,
         mechanisms due to their strong immunomodulatory capability (Shetty,   Gonçalves, R.M., 2018. Mesenchymal stromal cell secretome: influencing
                                                                 therapeutic potential by cellular pre-conditioning. Front. Immunol. 9, 2837.
         2020).In addition to MSCs, their derivatives including exosomes have   Gentile, P., Sterodimas, A., 2020. Adipose-derived Stromal Stem Cells (ASCs) As a New
         earned considerable interest as a therapeutic technique. Exosome-based   Regenerative Immediate Therapy Combating Coronavirus (COVID-19)-induced
         therapy is an attractive strategy for achieving the therapeutic benefits of   Pneumonia. Taylor & Francis.
                                                              Ghorbani, F., Feizabadi, M., Farzanegan, R., Vaziri, E., Samani, S., Lajevardi, S., et al.,
         MSCs without the complications and difficulties of the cells to the pa-  2017. An investigation of topics and trends of tracheal replacement studies using co-
         tients. In particular, the possible use of exosomes in preclinical models to   occurrence analysis. Tissue Eng. Part B Rev. 23 (2), 118–127.
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