A Comprehensive Review on Factors Influences Biogenesis, Functions, Therapeutic and Clinical Implications of Exosomes

Figures & data

Figure 1 Biogenesis and cargoes of exosomes.

Figure 2 Effect of various factors on biogenesis of exosomes.

Figure 3 Serum deprivation causes an increase of the number of cellular exosomes in THP-1 cells. Panel (A); 10% FCS. Panel (B); 1% FCS. Panel (C) Quantification of exosomes using DLS and NTA.

Figure 4 Multifunctional aspects biological functions of exosomes.

Figure 5 Therapeutic potential and versatile clinical implications of exosomes.

Table 1 Summary of the Exosome Used in Clinical Trials (Source: clinicaltrials.com)

S. No.	Type of Disease	Year/Phase/No. of Patients	Dose	Type of Administration	Results
1	Melanoma	2000 Phase I n=15	4×10^13 or 1.3×10^13 MHC Class II Molecules	SC (90% of the volume) and ID (10%) injections weekly for 4 weeks	No Grade II toxicity; No detected MAGE3‑specific CD4+ and CD8+ T cells
2	Non‑small cell lung cancer	Not reported Phase I n=4	1.3×10^13 MHC Class II Molecules	SC (90% of the volume) and ID (10%) injections weekly for 4 weeks	Well‑tolerated and only Grade 1‑2 adverse events; MAGE‑specific T‑cell responses in 1/3 patients; increased NK lytic activity in 2/4 patients
3	Non‑small cell lung cancer	May 2010 Phase II n=22	8.5×10^11‑1.0 x10^13 MHC Class II Molecules	Four ID at 1‑week Intervals	One patient had Grade 3 hepatotoxicity; boosting the NK cell arm of antitumor immunity
4	Colon cancer	Not reported, Phase I n=40	100‑500 μg of protein	Four SC at weekly Intervals	Safe, well‑tolerated; tumor‑specific antitumor CTL response in exosome plus GM‑CSF group
5	Chronic kidney diseases	April 2014 Phase II/III n=40	100 μg/kg/dose	Two doses of MSC‑EVs, Intra-arterial and intravenous injections	Safe, well‑tolerated; improved kidney function; decreased inflammation
6	Colon cancer (NCT01294072)	January 2011 Phase I n=35	Not reported	Tablets taken daily for 7 days	Active, not recruiting
7	Radiation‑ and chemotherapy‑induced Oral mucositis (NCT01668849)	August 2012 Phase I n=60	Not reported	Oral administration daily for 35 days	Active, not recruiting
8	Malignant ascites and pleural effusion (NCT01854866)	May 2013 Phase II n=30	Not reported	Perfused to the pleural or peritoneal cavity, 4 times/week	Unknown status
9	Type 1 diabetes (NCT02138331)	April 2014 Phase I n=20	(1.22‑1.51)×10^6 cells/kg, Day 0 and 7	Intravenous	Unknown status
10	Malignant pleural effusion (NCT02657460)	January 2016 Phase II n=90	Not reported	Not reported	Recruiting
11	Macular holes (NCT03437759)	March 2017 Phase I n=44	50 or 20 µg	Dripped into vitreous cavity	Recruiting
12	Bronchopulmonary dysplasia (NCT03857841)	June 2019 Phase I n=18	200 pmol phospholipid/Kg	Intravenous	Recruiting
13	Acute ischemic stroke (NCT03384433)	April 2019 Phase I/II n=5	200 μg	Stereotaxic injection	Not yet recruiting
14	Metastatic pancreatic cancer (NCT03608631)	March 2020 Phase I n=28	Not reported	IV on days 1, 4, and 10. Treatment repeated every 14 days for up to 3 courses	Not yet recruiting