A Tolerance Clinical Study on Aerosol Inhalation of Mesenchymal Stem Cells Exosomes In Healthy Volunteers
Condition: Healthy
MeSH terms: Respiratory Aspiration
Study type: Interventional
Phase: Phase 1

Summary: 
      Exosomes are naturally occurring nanosized vesicles and comprised of natural lipid bilayers
      with the abundance of adhesive proteins that readily interact with cellular membranes. These
      vesicles have a content that includes cytokines and growth factors, signaling lipids, mRNAs,
      and regulatory miRNAs. Exosomes are involved in cell-to-cell communication, cell signaling,
      and altering cell or tissue metabolism at short or long distances in the body, and can
      influence tissue responses to injury, infection, and disease.

      Experimental studies have demonstrated that mesenchymal stem cells (MSCs) or their exosomes
      (MSCs-Exo) significantly reduced lung inflammation and pathological impairment resulting from
      different types of lung injury. In addition, macrophage phagocytosis, bacterial killing and
      outcome were improved. It is highly likely that MSCs-Exo have the similar therapeutic effect
      on inoculation pneumonia as MSCs themselves.

      This clinical study will be performed to evaluate the safety and tolerance of aerosol
      inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo)
      in healthy volunteers.
    

Detailed description: 
      Experimental studies have demonstrated that mesenchymal stem cells (MSCs) or their exosomes
      (MSCs-Exo) significantly reduced lung inflammation and pathological impairment resulting from
      different types of lung injury. In addition, macrophage phagocytosis, bacterial killing and
      outcome were improved. It is highly likely that MSCs-Exo have the similar therapeutic effect
      on inoculation pneumonia as MSCs themselves.

      Although human bone marrow MSCs have been safely administered in patients with ARDS and
      septic shock (phase I/II trials), it seems safer to deliver MSCs-Exo rather than live MSCs.
      The intravenous administration of MSCs may result in aggregating or clumping in the injured
      microcirculation and carries the risk of mutagenicity and oncogenicity, which do not exist by
      treating with nebulized MSCs-Exo. Another advantage of MSCs-Exo over MSCs is the possibility
      of storing them for several weeks/months allowing their safe transportation and delayed
      therapeutic use.

      The purpose of this study, therefore, is to explore the safety and efficiency as well as
      provide a clinical dose reference for the subsequent trails of aerosol inhalation of MSCs-Exo
      in the treatment of severe lung diseases (including severe lung infection, acute respiratory
      distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD), etc.)
    

Intervention name(s): 1X level of MSCs-Exo; 2X level of MSCs-Exo; 4X level of MSCs-Exo; 6X level of MSCs-Exo; 8X level of MSCs-Exo
Intervention type(s): Biological; Biological; Biological; Biological; Biological
Intervention description(s): Once aerosol inhalation of MSCs-derived exosomes (2.0*10^8 nano vesicles/3 ml); Once aerosol inhalation of MSCs-derived exosomes (4.0*10^8 nano vesicles/3 ml); Once aerosol inhalation of MSCs-derived exosomes (8.0*10^8 nano vesicles/3 ml); Once aerosol inhalation of MSCs-derived exosomes (12.0*10^8 nano vesicles/3 ml); Once aerosol inhalation of MSCs-derived exosomes (16.0*10^8 nano vesicles/3 ml)
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: MSCs-exosomes
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: mesenchymal stem cells; exosomes; mesh nebulizer