A Tolerance Clinical Study on Aerosol Inhalation of Mesenchymal Stem Cells Exosomes In Healthy Volunteers

Study Overview
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Brief Summary
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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
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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.)

Official Title
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A Tolerance Clinical Study On Aerosol Inhalation of Mesenchymal Stem Cells Exosomes In Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Biological: 1X level of MSCs-Exo
* Biological: 2X level of MSCs-Exo
* Biological: 4X level of MSCs-Exo
* Biological: 6X level of MSCs-Exo
* Biological: 8X level of MSCs-Exo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers. Age: 19-45, males and females. The weight is within ± 10% of the standard weight [standard weight (kg) = 0.7 × (height cm-80)]. Examination indices of heart, liver, kidney and blood are all within the normal range. According to Good Clinical Practice (GCP), volunteers who understand and voluntarily sign the consent form before this study. Exclusion Criteria: Women in pregnancy or lactation. Primary diseases of important organs. Mentally or physically disabled patients. Suspected or definite history of alcohol and drug abuse. According to the investigator's judgment, there is a low possibility of enrollment (such as frailty, etc.). Volunteers who are allergic to the components of this medicine, or have a history of allergies to two or more drugs or food. Volunteers who have diseases (such as insomnia) and are using other preventive and therapeutic drugs before this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: MSCs-exosomes
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1X level<br>Aerosol inhalation of MSCs-derived exosomes treatment participants will receive once aerosol inhalation of MSCs-derived exosomes (2.0*10^8 nano vesicles/3 ml) | Biological: 1X level of MSCs-Exo<br>* Once aerosol inhalation of MSCs-derived exosomes (2.0*10^8 nano vesicles/3 ml)<br>|
| Experimental: 2X level<br>Aerosol inhalation of MSCs-derived exosomes treatment participants will receive once aerosol inhalation of MSCs-derived exosomes (4.0*10^8 nano vesicles/3 ml) | Biological: 2X level of MSCs-Exo<br>* Once aerosol inhalation of MSCs-derived exosomes (4.0*10^8 nano vesicles/3 ml)<br>|
| Experimental: 4X level<br>Aerosol inhalation of MSCs-derived exosomes treatment participants will receive once aerosol inhalation of MSCs-derived exosomes (8.0*10^8 nano vesicles/3 ml) | Biological: 4X level of MSCs-Exo<br>* Once aerosol inhalation of MSCs-derived exosomes (8.0*10^8 nano vesicles/3 ml)<br>|
| Experimental: 6X level<br>Aerosol inhalation of MSCs-derived exosomes treatment participants will receive once aerosol inhalation of MSCs-derived exosomes (12.0*10^8 nano vesicles/3 ml) | Biological: 6X level of MSCs-Exo<br>* Once aerosol inhalation of MSCs-derived exosomes (12.0*10^8 nano vesicles/3 ml)<br>|
| Experimental: 8X level<br>Aerosol inhalation of MSCs-derived exosomes treatment participants will receive once aerosol inhalation of MSCs-derived exosomes (16.0*10^8 nano vesicles/3 ml) | Biological: 8X level of MSCs-Exo<br>* Once aerosol inhalation of MSCs-derived exosomes (16.0*10^8 nano vesicles/3 ml)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Reaction (AE) and Severe Adverse Reaction (SAE) | Safety evaluation within 7 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE) | from Day 0 to Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mesenchymal stem cells, exosomes, mesh nebulizer