Mesenchymal stem cells and COVID-19: What they do and what they can do

Table 1 Summary of clinical trials listed in clinicaltrials.org involving mesenchymal stem cells in the treatment of coronavirus disease 2019

	NCT number	Title	Phases	Study designs	Cells/products	No. of cells	No. of infusions	Delivery route	No. of patients	Status	Location
1	NCT04366271	Clinical trial of allogeneic mesenchymal cells from umbilical cord tissue (UC) in patients with COVID-19	Phase 2	Randomized/parallel assignment/open label	UC-MSCs	Not reported	1	Not reported	106	Recruiting	Spain
2	NCT04444271	Mesenchymal stem cell infusion for COVID-19 infection	Phase 2	Randomized/parallel assignment/open label	BM-MSCs	2 × 106/kg	1 or 2	IV	20	Recruiting	Pakistan
3	NCT04416139	Mesenchymal stem cell for acute respiratory distress syndrome (ARDS) due for COVID-19	Phase 2	Non-randomized/parallel assignment/open label	UC-MSCs	1 × 106/kg	1	IV	10	Recruiting	Mexico
4	NCT04713878	Mesenchymal stem cells therapy in patients with COVID-19 pneumonia	Not applicable	Randomized/parallel assignment/open label	MSCs	1 × 106/kg	3	IV	21	Completed	Turkey
5	NCT04352803	Adipose mesenchymal cells for abatement of SARS-COV-2 respiratory compromise in COVID-19 disease	Phase 1	Non-randomized/sequential assignment/open label	Autologous AD-MSCs	5 × 105/kg	1	IV	20	Not yet recruiting	United States
6	NCT04565665	Cord blood-derived mesenchymal stem cells (MSCs) for the treatment of COVID-19 related ARDS	Phase 1	Randomized/parallel assignment/open label	UC-MSCs	Not reported	1 or 2	IV	70	Recruiting	United States
7	NCT04429763	Safety and efficacy of MSCs in the management of severe COVID-19 pneumonia	Phase 2	Randomized/parallel assignment/masking: Triple	UC-MSCs	1 × 106/kg	1	IV	30	Not yet recruiting	Colombia
8	NCT04456361	Use of MSCs in ARDS caused by COVID-19	Early Phase 1	Single group assignment/open label	WJ-MSCs	1 × 108	1	IV	9	Active, not recruiting	Mexico
9	NCT04315987	NestaCell® MSC to treat patients with severe COVID-19 pneumonia	Phase 2	Randomized/parallel assignment/quadruple masking	NestaCell®	2 × 107/kg	4	IV	90	Not yet recruiting	Brazil
10	NCT04366323	Clinical trial to assess the safety and efficacy of intravenous administration of allogeneic adult MSCs of expanded adipose tissue in patients with severe pneumonia due to COVID-19	Phase 1/phase 2	Randomized/parallel assignment/open label	AD-MSCs	8 × 107	2	IV	26	Active, not recruiting	Spain
11	NCT04611256	MSCs in patients diagnosed with COVID-19	Phase 1	Randomized/parallel assignment/open label	AD-MSCs	1 × 106/kg	2	IV	20	Recruiting	Mexico
12	NCT04625738	Efficacy of infusions of MSC from Wharton jelly in the SARS-Cov-2 (COVID-19) related ARDS	Phase 2	Randomized/parallel assignment/masking: Quadruple	WJ-MSCs	2 × 10/kg	3	IV	30	Not yet recruiting	France
13	NCT04252118	MSC treatment for pneumonia patients infected with COVID-19	Phase 1	Non-randomized/parallel assignment/open label	MSCs	3 × 107/kg	3	IV	20	Recruiting	China
14	NCT04346368	Bone marrow-derived MSC treatment for severe patients with COVID-19	Phase 1/phase 2	Randomized/parallel assignment/masking: single (participant)	BM-MSCs	1 × 106/kg	1	IV	20	Not yet recruiting	China
15	NCT04313322	Treatment of COVID-19 patients using Wharton's jelly-MSCs	Phase 1	Single group assignment/open label	WJ-MSCs	1 × 106/kg	3	IV	5	Recruiting	Jordan
16	NCT04288102	Treatment with human UC-derived MSCs for severe COVID-19	Phase 2	Randomized/parallel assignment/double-blind/placebo controlled	UC-MSCs	4 × 107/kg	3	IV	100	Completed	China
17	NCT04629105	Regenerative medicine for COVID-19 and flu-elicited ARDS using longeveron MSCs (LMSCs) (recover)	Phase 1	Randomized/parallel assignment/double-blind	LMSCs	1 × 108	3	IV	70	Recruiting	United States
18	NCT04382547	Treatment of COVID-19 associated pneumonia with allogenic pooled olfactory mucosa-derived MSCs	Phase 1/phase 2	Non-randomized/parallel assignment/open label	Allogenic pooled olfactory mucosa-derived MSCs	Not reported	Not reported	IV	40	Enrolling by invitation	Belarus
19	NCT04336254	Safety and efficacy study of allogeneic human dental pulp MSCs to treat severe COVID-19 patients	Phase 1/phase 2	Randomized/parallel assignment/masking: Triple	Allogeneic human dental pulp stem cells	3 × 107/kg	3	IV	20	Recruiting	China
20	NCT04527224	Study to evaluate the efficacy and safety of AstroStem-V in treatment of COVID-19 pneumonia	Phase 1/phase 2	Single group assignment/open label	AstroStem-V (AD-MSCs)	Not reported	Not reported	Not reported	10	Not yet recruiting	NA
21	NCT04273646	Study of human UC MSCs in the treatment of severe COVID-19	Not applicable	Randomized/parallel assignment/open label	UC-MSCs	0.5 × 106/kg	4	IV	48	Not yet recruiting	China
22	NCT04302519	Novel coronavirus induced severe pneumonia treated by dental pulp MSCs	Early phase 1	Single group assignment/open label	Dental pulp MSCs	1 × 106/kg	3	IV	24	Not yet recruiting	China
23	NCT04728698	Study of intravenous administration of allogeneic adipose-derived MSCs for COVID-19-induced acute respiratory distress	Phase 2	Randomized/parallel assignment/masking: Double	COVI-MSC (AD-MSCs)	1-1.5 × 106/kg	1	IV	100	Not yet recruiting	United States
24	NCT04457609	Administration of allogenic UC-MSCs as adjuvant therapy for critically-ill COVID-19 Patients	Phase 1	Randomized/parallel assignment/masking: Triple	UC-MSCs	1 × 106/kg	1	IV	40	Recruiting	Indonesia
25	NCT04348435	A randomized, double-blind, placebo-controlled clinical trial to determine the safety and efficacy of Hope Biosciences allogeneic adipose-derived mesenchymal stem cell therapy (HB-adMSCs) to provide protection against COVID-19	Phase 2	Randomized/parallel assignment/masking: Quadruple	AD-MSCs	G1: 2 × 108; G2: 1 × 108; G3: 5 × 107	5	IV	100	Enrolling by invitation	United States
26	NCT04349631	A clinical trial to determine the safety and efficacy of HB-adMSCs to provide protection against COVID-19	Phase 2	Single group assignment/open label/primary purpose: Prevention	AD-MSCs	Not reported	5	IV	56	Active, not recruiting	United States
27	NCT04366063	MSC therapy for SARS-CoV-2-related ARDS	Phase 2/phase 3	Randomized/parallel assignment/open label	MSCs and EVs from MSCs	G1: 1 × 108 MSC; G2: 1 × 108 MSCs + EVs	2	IV	60	Recruiting	Iran
28	NCT04339660	Clinical research of human MSCs in the treatment of COVID-19 pneumonia	Phase 1/phase 2	Randomized/parallel assignment/masking: Triple	UC-MSCs	1 × 106/kg	1	IV	30	Recruiting	China
29	NCT04428801	Autologous adipose-derived stem cells (AdMSCs) for COVID-19	Phase 2	Randomized/parallel assignment/masking: Double	Autologous AD-MSCs	2 × 108	3	IV	200	Not yet recruiting	United States
30	NCT04573270	MSCs for the treatment of COVID-19	Phase 1	Randomized/single group assignment/masking: triple	PrimePro (UC-MSCs)	Not reported	1	IV	40	Completed	United States
31	NCT04490486	UC derived MSCs versus placebo to treat acute pulmonary inflammation due to COVID-19	Phase 1	Randomized/parallel assignment/masking: Double	UC-MSCs	1 × 108	2	IV	21	Not yet recruiting	United States
32	NCT04355728	Use of UC-MSCs for COVID-19 patients	Phase 1/Phase 2	Randomized/parallel assignment/masking: triple	UC-MSCs + heparin	1 × 108	2	IV	24	Completed	United States
33	NCT04371601	Safety and effectiveness of MSCs in the treatment of pneumonia of COVID-19	Early Phase 1	Randomized/parallel assignment/open label	UC-MSCs	1 × 106/kg	4	IV	60	Active, not recruiting	China
34	NCT04522986	An exploratory study of adr-001 in patients with severe pneumonia caused by SARS-CoV-2 Infection	Phase 1	Single group assignment/open label	AD-MSCs (ADR-001)	1 × 108	4	IV	6	Not yet recruiting	Japan
35	NCT04390152	Safety and efficacy of intravenous Wharton's jelly derived MSCs in ARDS due to COVID 19	Phase 1/Phase 2	Randomized/parallel assignment/masking: Quadruple	WJ-MSCs	5 × 107	2	IV	40	Recruiting	Colombia
36	NCT04461925	Treatment of coronavirus COVID-19 pneumonia (pathogen SARS-CoV-2) with cryopreserved allogeneic P_MMSCs and UC-MMSCs	Phase 1/phase 2	Non-randomized/parallel assignment/open label	Placenta-derived MSCs	1 × 106/kg	3	IV	30	Recruiting	Ukraine
37	NCT04348461	BAttLe against COVID-19 using mesenchymal stromal cells	Phase 2	Randomized/parallel assignment/masking: Quadruple	Allogeneic and expanded AD-MSCs	1.5 × 106/kg	2	IV	100	Not yet recruiting	Spain
38	NCT04535856	Therapeutic study to evaluate the safety and efficacy of DW-MSC in COVID-19 patients	Phase 1	Randomized/parallel assignment/masking: Quadruple	DW-MSCs	G1: 5 × 107; G2: 10 × 107	1	IV	9	Completed	Indonesia
39	NCT04362189	Efficacy and safety study of allogeneic HB-adMSCs for the treatment of COVID-19	Phase 2	Randomized/parallel assignment/masking: Quadruple	AD-MSCs	1 × 108	4	IV	100	Active, not recruiting	United States
40	NCT04494386	UC lining stem cells (ULSC) in patients with COVID-19 ARDS	Phase 1/Phase 2	Randomized/parallel assignment/masking: Triple	UC-MSCs	1 × 108	1 or 2	IV	60	Recruiting	United States
41	NCT04397796	Study of the safety of therapeutic tx with immunomodulatory MSC in adults with COVID-19 infection requiring mechanical ventilation	Phase 1	Randomized/parallel assignment/masking: Quadruple	BM-MSCs	Not reported	Not reported	Not reported	45	Recruiting	United States
42	NCT04345601	Mesenchymal stromal cells for the treatment of SARS-CoV-2 induced acute respiratory failure (COVID-19 Disease)	Phase 1/Phase 2	Randomized/parallel assignment/open label	MSCs	1 × 108/kg	Up to 2	IV	30	Recruiting	United States
43	NCT04452097	Use of hUC-MSC product (BX-U001) for the treatment of COVID-19 with ARDS	Phase 1/phase 2	Non-randomized/sequential assignment/open label	UC-MSCs	G1: 0.5 × 106; G2: 1 × 106; G3: 1.5 × 106	1	IV	39	Not yet recruiting	United States
44	NCT04492501	Investigational treatments for COVID-19 in tertiary care hospital of Pakistan	Not applicable	Non-randomized/factorial assignment/open label	BM-MSCs (+ TPE and convalescent plasma)	2 × 106/kg	1	IV	600	Completed	Pakistan
45	NCT04377334	MSCs in inflammation-resolution programs of COVID-19 induced ARDS	Phase 2	Randomized/parallel assignment/open label	BM-MSCs	Not reported	Not reported	IV	40	Not yet recruiting	Germany
46	NCT04390139	Efficacy and safety evaluation of MSCs for the treatment of patients with respiratory distress due to COVID-19	Phase 1/phase 2	Randomized/parallel assignment/masking: Quadruple	WJ-MSCs	1 × 106/kg	2	IV	30	Recruiting	Spain
47	NCT04467047	Safety and feasibility of allogenic MSC in the treatment of COVID-19	Phase 1	Single group assignment/open label	MSCs	1 x 106/kg	1	IV	10	Not yet recruiting	Brazil
48	NCT04392778	Clinical use of stem cells for the treatment of COVID-19	Phase 1/phase 2	Randomized/parallel assignment/masking: Quadruple	UC-MSCs	3 × 106/kg	3	IV	30	Recruiting	Turkey
49	NCT04537351	The MEseNchymal COVID-19 trial: a pilot study to investigate early efficacy of MSCs in adults with COVID-19	Phase 1/phase 2	Randomized/parallel assignment/open label	CYP-001 (Cymerus® MSC)	up to 2 × 106/kg	2	IV	24	Recruiting	Australia
50	NCT04361942	Treatment of severe COVID-19 pneumonia with allogeneic mesenchymal stromal cells (COVID_MSV)	Phase 2	Randomized/parallel assignment/masking: Triple	MSCs	1 × 106/kg	1	IV	24	Recruiting	Spain
51	NCT04398303	ACT-20 in patients with severe COVID-19 pneumonia	Phase 1/phase 2	Randomized/Parallel Assignment/Double-blind	UC-MSCs and conditioned UC-MSCs	G1: 1 × 106 G2: 100 mL conditioned media (MD)	1	IV	70	Not yet recruiting	United States
52	NCT03042143	Repair of ARDS by stromal cell administration (realist) (COVID-19)	Phase 1/phase 2	Randomized/parallel assignment/masking: Quadruple	hUC-derived CD362 enriched MSCs	400 × 106	1	IV	75	Recruiting	United Kingdom
53	NCT04269525	UC-derived MSCs treatment for the 2019-novel coronavirus (nCOV) pneumonia	Phase 2	Single group assignment/open label/primary purpose: Prevention	UC-MSCs	9.9 × 107	4	IV	16	Recruiting	China
54	NCT04602442	Safety and efficiency of method of exosome inhalation in COVID-19 associated pneumonia	Phase 2	Randomized/parallel assignment/masking: Double	EXO-1 and EXO-2 (exosomes from MSC)	0.5-2 × 1010 nanoparticles	20 (2/d for 20 d)	Aerosol inhalation	90	Enrolling by invitation	Russia
55	NCT04437823	Efficacy of intravenous infusions of stem cells in the treatment of COVID-19 patients	Phase 2	Randomized/parallel assignment/open label	UC-MSCs	5 × 105/kg	3	IV	20	Recruiting	Pakistan
56	NCT04371393	MSCs in COVID-19 ARDS	Phase 3	Randomized/parallel assignment/masking: Triple	Remestemcel-L	2 × 106/kg	2	IV	223	Active, not recruiting	United States
57	NCT04333368	Cell therapy using UC-derived mesenchymal stromal cells in SARS-CoV-2-related ARDS	Phase 1/phase 2	Randomized/parallel assignment/masking: Triple	WJ-UC-MSCs	1 × 106/kg	3	IV	47	Active, not recruiting	France
58	NCT04447833	Mesenchymal stromal cell therapy for the treatment of ARDS	Phase 1	Single group assignment/open label	KI-MSC-PL-205 (BM-MSCs)	1-2 × 106/kg	1	IV	9	Recruiting	Sweden
59	NCT04491240	Evaluation of safety and efficiency of method of exosome inhalation in SARS-CoV-2 associated pneumonia	Phase 1/phase 2	Randomized/parallel assignment/masking: Double	Drug: EXO-1 and EXO- (exosomes from MSCs)	0.5-2 × 1010 nanoparticles	20 (2/d for 20 d)	Aerosol inhalation	30	Completed	Russia
60	NCT04299152	Stem cell educator therapy treat the viral inflammation in COVID-19	Phase 2	Randomized/parallel assignment/masking: Single (care provider)	Stem Cell Educator (from UC-MSCs)	Not reported	1	IV	20	Not yet recruiting	United States
61	NCT04466098	Multiple dosing of mesenchymal stromal cells in patients with ARDS (COVID-19)	Phase 2	Randomized/parallel assignment/masking: Triple	MSCs	3 × 108	3	IV	30	Recruiting	United States
62	NCT04524962	Study of descartes-30 in ARDS	Phase 1/phase 2	Single group assignment/open label	Descartes 30 (MSCs RNA-engineered to secrete a combination of DNases)	Not reported	Not reported	Not reported	30	Recruiting	United States
63	NCT04445220	A study of cell therapy in COVID-19 subjects with acute kidney injury who are receiving renal replacement therapy	Phase 1/phase 2	Randomized/parallel assignment/masking: Quadruple	Allogeneic MSCs (SBI-101)	G1: 2.5 × 108; G2: 7.5 × 108	Not reported	Not reported	22	Recruiting	United States
64	NCT04400032	Cellular immuno-therapy for COVID-19 ARDS vanguard	Phase 1	Non-randomized/sequential assignment/open label	BM-MSCs	G1: 2.5 × 107; G2: 5 × 107; G3: 9 × 107	3	IV	9	Recruiting	Canada
65	NCT04615429	Clinical trial to assess the efficacy of MSC in patients with ARDS due to COVID-19	Phase 2	Randomized/Parallel Assignment/Double-blind	MSCs	1 × 106/kg	1	IV	20	Recruiting	Spain
66	NCT04525378	MSC-based therapy in COVID-19-associated ARDS	Phase 1	Randomized/parallel assignment/open label	MSCs	G1: 2.5 × 107 G2: 5 × 107 G3: 10 × 107	G1 and G2: 2 G3: 1	IV	20	Recruiting	Brazil
67	NCT04399889	hCT-MSCs for COVID19 ARDS	Phase 1/phase 2	Randomized/single group assignment/masking: Quadruple	Human cord tissue MSCs	1 × 106/kg	3	IV	30	Recruiting	United States
68	NCT04445454	Mesenchymal stromal cell therapy for severe COVID-19 infection	Phase 1/phase 2	Single group assignment/open label	BM-MSCs	1.5-3.0 × 106/kg	3	IV	20	Recruiting	Belgium
69	NCT04276987	A pilot clinical study on inhalation of MSCs exosomes treating severe novel coronavirus pneumonia	Phase 1	Single group assignment/open label	AD-MSCs-derived exosomes	2 × 108 nanovesicles	5	Aerosol inhalation	24	Completed	China
70	NCT04482699	RAPA-501-Allo Off-the-shelf therapy of COVID-19	Phase 1/phase 2	Randomized/sequential assignment/masking: Double	RAPA-501-ALLO	G1: 4 × 107 G2: 1.6 × 108	Not reported	Not reported	88	Recruiting	United States
71	NCT04614025	Open-label multicenter study to evaluate the efficacy of PLX-PAD for the treatment of COVID-19	Phase 2	Randomized/parallel assignment/open label	PLX-PAD (placental MSC-like)	2 × 107	15	IM	40	Recruiting	Israel

COVID-19: Coronavirus disease 2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; MSCs: Mesenchymal stem cells; UC-MSCs: Umbilical cord mesenchymal stem cells; BM-MSCs: Bone marrow mesenchymal stem cells; AD-MSCs: Adipose tissue mesenchymal stem cells; WJ-MSCs: Wharton’s jelly mesenchymal stem cells; TPE: Total plasma exchange; NA: Not available.