TABLE 2.
Summary of the clinical trials evaluating the secretome of MSCs.
| NCT Number | Condition | Phases | Type of product | Match | Route of administration | Dose (106 cells) or MV or Exo | Cell expansion passage | Preconditioning | Status | Gender | Age (years) | Enrollment | Start date | Location | Funded bys | Study results |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02138331 | Type 1 Diabetes | Phase 2|Phase 3 | Cell free [UC-MSCs-MV and Exo] | NA | Intravenous | Exo or MV: from SN of 1.2–1.5/kg (MSCs) | NA | NA | Unknown status | All | 18–60 | 20 | April 2014 | Egypt | Other | NA |
| NCT04798716 | Covid -19 Acute Respiratory Distress Syndrome | Phase 1|Phase 2 | Cell free [Perinatal MSCs-Exo] | NA | Intravenous | Tree groups: Escalating Dose: 2/4/8; 8/4/8; 8/8/8 (x103/mL) | NA | NA | Not yet recruiting | All | 18 and older | 55 | April 2021 | United States | Industry | NA |
| NCT03437759 | Macular Holes | Early Phase 1 | Cell free [UC-MSCs-Exo] | NA | Intravitreal | 20–50 µg MSC-Exo | NA | NA | Active, not recruiting | All | Up to 80 | 44 | March 1, 2017 | China | Other | NA |
| NCT04276987 | Covid -19 Pneumonia | Phase 1 | Cell free [AD-MSCs-Exo] | Allogenic | Aerosol inhalation | 5 x (2 × 108 nv/mL) | NA | NA | Completed | All | 18–75 | 24 | February 15, 2020 | China | Other|Industry | NA |
| NCT04356300 | Multiple Organ Dysfuntion Syndrome | Not Applicable | Cell free [UC-MSCs-Exo] | NA | Intravenous | (14x) 150 mg/day | NA | NA | Not yet recruiting | All | 20–80 | 60 | September 1, 2020 | NA | Other | NA |
| NCT04388982 | Alzheimer Disease | Phase 1|Phase 2 | Cell free [AD-MSCs-Exo] | Allogenic | Nasal drip | 5–10–20 µg (2x/W) for 12 W | NA | NA | Recruiting | All | 50 and older | 9 | July 1, 2020 | China | Other|Industry | NA |
| NCT03384433 | Ischemic Stroke | Phase 1|Phase 2 | Cell free [MSCs-Exo] | Allogenic | Stereotaxis/Intraparanchymal | NA | NA | Exosome enriched by miR-124 | Recruiting | All | 40–80 | 5 | April 17, 2019 | Iran | Other | NA |
| NCT04313647 | Healthy Volunteers: Tolerance test | Phase 1 | Cell free [AD-MSCs-Exo] | Allogenic | Aerosol inhalation | 2-4-8–12–16–20 (x108 nv/3 ml) | NA | NA | Recruiting | All | 18–45 | 27 | March 16, 2020 | China | Other|Industry | NA |
| NCT04850469 | Severely Infected Children | NA | NA | NA | NA | NA | NA | NA | Not yet recruiting | All | Up to 18 | 200 | January 1, 2022 | China | Other | NA |
| NCT04173650 | Dystrophic Epidermolysis Bullosa | Phase 1|Phase 2 | Cell free [BM-MSCs-Exo] | Allogenic | Local | 6 ascending doses | NA | NA | Not yet recruiting | All | 6 and older | 10 | April 2021 | NA | Industry | NA |
| NCT03608631 | Metastatic Pancreas Cancer | Phase 1 | Cell free [MSCs-Exo with KRAS G12D siRNA] | NA | Intravenous | (15–20 min on days 1, 4, and 10); 3 courses/14 days | NA | KrasG12D siRNA-loaded MSCs-Exo | Recruiting | All | 18 and older | 28 | January 27, 2021 | United States | Other | NA |
| NCT04602442 | Covid--19 Pneumonia | Phase 2 | Cell free [MSCs-Exo] | NA | Aerosol inhalation | 2x (0,5–2 x1010 nanoparticles)/10 days | NA | NA | Enrolling by invitation | All | 18–65 | 90 | October 1, 2020 | Russian Federation | Other | NA |
| NCT04491240 | Covid--19 Pneumonia | Phase 1|Phase 2 | Exosomes | NA | Aerosol inhalation | 2x (0,5–2 x1010 nanoparticles)/10 days | NA | NA | Completed | All | 18–65 | 30 | July 20, 2020 | Russian Federation | Other | NA |
| NCT03857841 | Bronchopulmonary Dysplasia | Phase 1 | Cell free [BM-MSCs-EVs] UNEX-42 | NA | Intravenous | 20–60–200 pmol EV/kg | NA | NA | Terminated | All | Up to 14 days | 3 | June 20, 2019 | United States | Industry | NA |
| NCT04213248 | Dry Eye | Phase 1|Phase 2 | Cell free [UC-MSCs-Exo] | NA | Artificial tears | 10ug/drop, (4x)/day (14 days) | NA | NA | Recruiting | All | 18–70 | 27 | February 18, 2020 | China | Other | NA |
| Kordelas et al., 2014 | Graft-Versus-Host-Disease | NA | Cell free [BM-MSCs-Exo] | Allogenic | Intravenous | 1.3–3.5 × 1010 particles/unit; 0.5–1.6 mg/unit) | 3 | NA | Completed | Female | 22 | 1 | NA | Germany | — | The clinical GvHD symptoms improved significantly shortly after the start of the MSC-exosome therapy. Kordelas et al., 2014. doi:10.1038/leu.2014.41 |
| Nassar et al., 2016 | Chronic Kidney Diseases | Phase 2|Phase 3 | Cell free [UC-MSCs-EVs] | Allogenic | Intravenous/Intra-arterial | 100 μg EV/kg/dose (2 doses) | 6 | NA | Completed | All | 26–44 | 40 | NA | Egypt | Other | Administration of cell-free cord-blood mesenchymal stem cells derived extracellular vesicles (CF-CBMSCs-EVs) is safe and can ameliorate the inflammatory immune reaction and improve the overall kidney function in grade III-IV CKD patients. Nassar et al., 2016. doi 10.1186/s40824-016-0068-0 |
| NCT04270006 | Periodontitis | Early Phase 1 | Cell free [AD-MSCs-Exo] | Autologous | Local | NA | NA | NA | Recruiting | All | 18–50 | 10 | February 12, 2020 | Egypt | Other | NA |
| NCT04202783 | Craniofacial Neuralgia | Not Applicable | Neonatal stem cell -Exo | — | Focused ultrasound epineural injection and Intravenous | 2 x (5 ml concentrated Exo) + 45 mg Exo +15 mg Exo | NA | NA | Suspended | All | 18 and older | 100 | December 1, 2021 | United States | Other | NA |
| NCT04202770 | Depression, Anxiety, and Dementias | Not Applicable | Cell free (amniotic fluid-MSC-Exo) | Allogenic | Focused ultrasound Intravenous | Eq 20 stem cells | NA | NA | Suspended | All | 18 and older | 300 | December 1, 2019 | United States | Other | NA |
| NCT04384445 | COVID-19 Acute Respiratory Distress Syndrome | Phase 1|Phase 2 | Amniotic fluid stem cell organicell Flow) | — | Intravenous | 2–5 x 1011 particles/mL (3 times) | NA | NA | Recruiting | All | 18 and older | 20 | September 8, 2020 | United States | Industry | NA |
| NCT04223622 | Osteoarthritis | — | Cell free [AD-MSCs-CM or Evs) | — | ex vivo Osteoarthritis model | NA | NA | NA | Not yet recruiting | All | 18 and older | 24 | February 2020 | — | Other | NA |
| NCT04270006 | Periodontitis | Early Phase 1 | Cell free [AD-MSCs-Exo] | Autologous | Local | NA | NA | NA | Recruiting | All | 18–50 | 10 | February 12, 2020 | Egypt | Other | NA |
| NCT04134676 | Chronic Ulcer Wounds | Phase 1 | Cell free [WJ-MSCs-CM) | NA | Local | CM gel (for 2 w) | NA | NA | Completed | All | 18–80 | 38 | June 1, 2019 | Indonesia | Other|Industry | NA |
| NCT04544215 | Pulmonary Infection | Phase 1|Phase 2 | Cell free [AD-MSCs-Exo] | Allogenic | Aerosol inhalation | 8 × 108 or 16 × 108 nano vesicles/3 ml | NA | NA | Recruiting | All | 18–75 | 60 | July 1, 2020 | China | Other|Industry | NA |
| Sengupta et al | Severe COVID-19 | NA | Cell free [BM-MSCs-Exo] | Allogenic | Intravenous | 15 ml of ExoFlo | NA | NA | Completed | NA | 18–85 | 27 | April 2020 | United States | Other | Owing to its safety profile, capacity to restore oxygenation, downregulate cytokine storm, and reconstitute immunity, ExoFlo is a promising therapeutic candidate for severe COVID-19. Sengupta et al.(2020), doi: 10.1089/scd.2020.0080 |