Stem Cells International

Review Article

Mesenchymal Stem Cells and COVID-19: Cure, Prevention, and Vaccination

Table 1

A brief review of recent clinical trials using stem cell-based therapy for treatment of COVID-19.


Stem cell source: umbilical cord-derived stem cells (UC, WJ, placental–MSCs)
(age)	Route of administration	S	Clinical trial ID
20 (18-70)	3× IV ( cells/infusion at d 0, 3, 6)	R	NCT04252118 (China)
30 (≥18)	3× IV (details not specified)	R	ChiCTR2000030866 (China)
20 (16-75)	3× IV (2 doses: (10⁶ cells/kg in 1.25 ml) and ( cells/kg in 2.5 ml))	R	ChiCTR2000030835 (China)
16 (18-80)	4× IV (/50 ml/bag, 3 bags each time at days 1, 3, 5, and 7)	R	NCT04269525 (China)
9 (18-75)	IV (details not specified)	R	ChiCTR2000030300 (China)
48 (18-65)	4× IV ( at days 1, 3, 5, and 7)	NR	NCT04273646 (China)
60 (18-70)	(details not specified)	NR	ChiCTR2000030173 (China)
60 (16-75)	IV (details not specified)	NR	ChiCTR2000030138 (China)
16 (18-75)	IV (comparison of different doses, details not specified)	R	ChiCTR2000030116 (China)
60 (≥18)	IV (details not specified)	NR	ChiCTR2000029816 (China)
[17–74]	4× IV ( in 100 ml)	W	NCT04293692 (China)
10 (18-95)	3× IV ( at days 1, 3, and 6)	NR	IRCT20140528017891N8 (Iran)
40 (≥18)	1× IV (details not specified)	C	NCT04573270 (USA)
70 (≥18)	IV (at day 1, second infusion at day 7 according to physician discretion)	R	NCT04565665 (USA)
30 (18-70)	IV ()	NR	IRCT20200426047206N2 (Iran)
20 (18-70)	3× IV ( at days 1, 3, and 6)	R	IRCT20160809029275N1 (Iran)
30 (18-79)	IV ( cells/kg)	NR	NCT04429763
30 (18-75)	IV ( cell/kg in 100 ml of NS, second infusion at d 7 according to physician discretion)	R	NCT04339660 (China)
20 (30-70)	3× IV ( cell/kg at d 1, 3, 5)	R	NCT04437823 (Pakistan)
21 (≥18)	2× IV ( cell/kg at days 0 and 3)	NR	NCT04490486 (USA)
60 (18-70)	4× IV (10⁶ cell/kg/time every 4 days)	NR	NCT04371601 (China)
60 (≥18)	1 or 2× IV by 48 h interval (10⁶ cell/dose in NS)	R	NCT04494386 (USA)
40 (18-95)	1× IV ( in 100 ml of NS)	R	NCT04457609 (Indonesia)
40 (18-80)	IV ( cell/kg in 40 ml)	R	ChiCTR2000030088 (China)
5 (≥18)	3× IV (10⁶ cell/kg in 25 ml every 3 days)	R	NCT04313322 (Jordan)
40 (≥18)	3× IV ( cell/kg in a 150 ml, at days 1, 3, and 5)	R	NCT04333368 (France)
20 (18-65)	IV (2 doses: (10⁶ cells/kg in 1.25 ml) and ( cells/kg in 2.5 ml) at days 1 and 4)	NR	CTRI/2020/08/027043 (India)
20 (18-65)	1× IV (3 doses: ( cells (±10%) at days 0, 2, and 4)	R	IRCT20200413047063N1 (Iran)
6 (no limit)	3× IV ( cells/kg, once every 3-4 days during a 14-day period)	R	IRCT20200418047121N2 (Iran)
90 (18-85)	IV ( cell/kg, at days 1, 3, and 6)	R	IRCT20200421047150N1 (Iran)
40 (18-80)	IV ()	NR	NCT04390152 (Colombia)
9 (≥18)	1× IV ( cells)	NR	NCT04456361 (Mexico)
30 (18-75)	1× IV ( cells/kg at days 1 and 3)	R	NCT04390139 (Spain)
24 (≥18)	IV ( cells)	NR	NCT04355728 (USA)
Stem cell source: BM-MSCs
(age)	Route of administration	S	Clinical trial ID
20 (18-75)	IV ( at day 1)	NR	NCT04346368 (China)
20 (≥10)	IV ( cells/kg at day 1, second infusion at day 7 according to physician discretion)	R	NCT04444271 (Pakistan)
40 (≥18)	IV (details not specified)	NR	NCT04377334 (Germany)
45 (18-80)	IV (details not specified)	R	NCT04397796 (USA)
9 (18-65)	1× IV (2 doses: ( cells/kg) and ( cells/kg))	R	NCT04447833 (Sweden)
Stem cell source: Ad-MSCs
(age)	Route of administration	S	Clinical trial ID
26 (18-80)	IV ( cells)	R	NCT04366323 (Spain)
100 (≥18)	IV (2 serial doses of cells/kg)	NR	NCT04348461
20 (18-90)	IV ( cells)	NR	NCT04352803
10 (19-80)	(details not specified)	NR	NCT04527224
6 (≥20)	4× IV ( cells, once a week)	NR	JPRN-JapicCTI-205416 (Japan)
0 (18-80)	IV ( cells in 100 ml NS)	NR	NCT04341610 (Denmark)
56 (NL)	5 × IV (details not specified)	E	NCT04349631 (USA)
100 (NL)	5× IV (3 doses: ( cells), ( cells), and ( cells) at weeks 0, 2, 6, 10, and 14)	E	NCT04348435 (United States)
20 (18-80)	(details not specified)	NR	NCT04486001 (USA)
200 (≥18)	IV ( cells, every three days)	NR	NCT04428801
100 (NL)	4× IV ( cells at days 0, 3, 7, and 10)	NR	NCT04362189 (USA)
Stem cell source: Dp-MSCs
(age)	Route of administration	S	Clinical trial ID
24 (18-75)	3× IV (10⁶ cell/kg in 50 ml NS)	NR	NCT04302519 (China)
20 (18-65)	3× IV ( cells in 30 ml at days 1, 4, and 7)	R	NCT04336254(China)
20 (18-65)	IV (details not specified)	NR	ChiCTR2000031319 (China)
10 (18-95)	1× IV ( cells)	R	IRCT20140911019125N6 (Iran)
Stem cell source: not specified
(age)	Route of administration	S	Clinical trial ID
120 (18–95)	IV ( cells/kg in 100 ml of NS)	R	ChiCTR2000029990 (China)
100 (18-75)	3× IV ( cells/time at days 0, 3, and 6)	C	NCT04288102 (China)
120 (18-95)	(details not specified)	R	ChiCTR2000029990 (China)
20 (18-70)	4× IV (details not specified)	R	ChiCTR2000030020 (China)
32 (18-100)	IV (details not specified)	NR	ChiCTR2000030224 (China)
90 (≥18)	IV (3 or 4 cycles of cells at days 1, 3, 5, and 7)	NR	NCT04315987 (Brazil)
9 (18-70)	IV (3 doses: cells/kg)	R	NCT04331613 (China)
200 (18-80)	3× IV (details not specified)	R	ChiCTR2000031430 (China)
36 (18-90)	IV (details not specified)	R	ChiCTR2000031494 (China)
5 (18-70)	3× IV ( cells at days 0, 3, and 6)	NR	IRCT20200325046860N2 (Iran)
30 (40-60)	IV ( cells/kg at days 0, 3, and 6)	R	NCT04392778 (Turkey)
10 (≥18)	1× IV ( cells/kg)	R	NCT04416139 (Mexico)
6 (18-70)	3× IV ( (±10%) cells in 50 ml NS at days 0, 2, and 4)	NR	IRCT20200217046526N1 (Iran)
300 (≥18)	cells/kg, second infusion at 4 days following the first infusion (±1 day)	R	NCT04371393 (USA)
400 (18-89)	IV (details not specified)	R	NCT04367077 (USA)
24 (≥18)	IV ( cells/kg at days 1 and 3)	R	NCT04537351 (Australia)
9 (≥19)	IV (2 doses: ( cells) and ( cells))	NR	NCT04535856 (Indonesia)
MSC-EVs
(age)	Route of administration	S	Clinical trial ID
24 (18-75)	5× aerosol inhalation ( EV/3 ml at days 1, 2, 3, 4, and 5)	C	NCT04276987 (China)
26 (18-65)	Aerosol inhalation (details not specified)	NR	ChiCTR2000030261 (China)
64 (≥70)	IV (0.2 mg/kg in 15 ml at days 1 and 3)	R	ISRCTN33578935 (Germany)
MSCs + MSC-EVs
(age)	Route of administration	S	Clinical trial ID
90 (18-70)	UC-MSCs and exosomes IV ( cells/time, 1 time/week, 2 times/course, a total of 2 courses; exosomes: 180 mg/time, 1 time/day, 7 days/course, 2 courses in total)	NR	ChiCTR2000030484 (China)
60 (18-65)	MSCs + EVs 2× IV (3 doses: (±10%) cells at days 0 and 2) 2 × IV (MSC-EVs at d 4, 6)	R	NCT04366063 (IRCT20200217046526N2) (Iran)
Stem cell-based combination therapies
(age)	Route of administration	S	Clinical trial ID
70 (18-75)	MSCs + ruxolitinib (details not specified)	R	ChiCTR2000029580 (China)
30 (≥18)	UCB-MNC CM (details not specified)	NR	ChiCTR2000029569 (China)
75 (≥16)	UC-MSCs enriched with CD362 IV (maximum tolerated dose from the phase 1 trial)	R	NCT03042143 (UK)
20 (4-80)	NK + UC-MSCs (details not specified)	NR	ChiCTR2000030944 (China)
60 (≥18)	UCB-NK + UCB-MSC 3 doses: 5× IV ( every 2 days) and 3× IV ( NK + MSC every 2 days), and 1 IV ( NK + MSC in a week)	NR	ChiCTR2000029817 (China)
600 (18-90)	Convalescent plasma, mesenchymal stem cell therapy, remdesivir, and Tocilizumab, alone or in combination IV (2 doses: [100 × 10⁶ cells]and [200 × 10⁶ cells] at d 1, 4)	NR	NCT04492501 (Pakistan)
86 (≥18)	Human placental hematopoietic stem cell-derived NK cells (CYNK-001) IV (at days 1, 4, 7; details not specified)	R	NCT04365101 (USA)
146 (≥18)	Autologous nonhematopoietic peripheral blood stem cells (NHPBSC) (details not specified)	NR	NCT04473170 (United Arab Emirates)
30 (18-75)	Cryopreserved allogeneic P_MMSCs and UC-MMSCs 3× IV ( cells/kg/time, once every 3 days at days 1, 4, and 7)	R	NCT04461925 (Ukraine)
40 (18-70)	Allogenic pooled olfactory mucosa-derived MSCs (details not specified)	E	NCT04382547 (Belarus)
63 (1-99)	Hu menstrual blood SC + artificial liver IV (details not specified)	R	ChiCTR2000029606 (China)
20 (18-80)	ESC-derived M cells (CAStem) 2× IV ( cells/kg. The interval between each infusion was 1 week (±2 days). Second infusion at day 7 according to physician discretion.)	R	ChiCTR2000031139 (China)

: number of patients, S: status, R: recruiting, NR: not recruiting, NS; normal saline, IV: intravenous injection, NS: normal saline, MSCs: mesenchymal stem cells, UC: umbilical cord, WJ: Wharton jelly, BM: bone marrow, Ad: adipose, Dp: dental pulp, NK: natural killer cell, MSC-EVs: MSC-derived extracellular vesicles, UCB: umbilical cord blood, MNC: mononuclear cells, CM: conditioned medium.