Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases: Recent advancements and prospects

Table 1 Clinical trials of umbilical cord mesenchymal stem cells therapy for patients with coronavirus disease 2019

No	Trial ID	UC-MSCs administration protocol			Phase	Status	Patients	Age (yr)	Follow-up time	Mask	Allocation	Country
		Frequency	Dose (cells)	Route
1	NCT04293692	4 (at days 1, 3, 5 and 7)	0.5 × 106/kg	IV	N/A	Withdrawn	48	18-75	N/A	Triple-blind	Randomized	China
2	NCT05682586	2 (at days 1 and 4)	1 × 106/kg	IV	III	Recruiting	60	18-75	N/A	Open-label	Randomized	China
3	NCT05501418	1	N/A	IV	I/II	Active, not recruiting	75	20-80	12 months	Single-blind	Randomized	China
4	NCT05719012	3 (at months 1, 2, and 3)	N/A	IV	II	Not yet recruiting	70	18-80	96 wk	Triple-blind	Randomized	China
5	NCT04273646	4 (at days 1, 3, 5 and 7)	0.5 × 106/kg	IV	N/A	Unknown	48	18-65	96 wk	Open-label	Randomized	China
6	NCT05689008	2 (at days 1 and 4)	1 × 106/kg	IV	III	Recruiting	60	18-85	N/A	Open-label	Randomized	China
7	NCT04457609	1	1 × 106/kg	IV	I	Unknown	40	18-95	N/A	Triple-blind	Randomized	Indonesia
8	NCT05132972	3 (at days 0, 3, and 6)	1 × 106/kg	IV	II/III	Recruiting	42	18-75	90 d	Quadruple-blind	Randomized	Indonesia
9	NCT04288102	3 (at days 0, 3, and 6)	4.0 × 107	IV	II	Completed	100	18-75	90 d	Quadruple-blind	Randomized	China
10	NCT04366271	1	N/A	N/A	II	Withdrawn	100	40-80	N/A	Open-label	Randomized	Spain
11	NCT04371601	4 (once every 4 d)	1 × 106/kg	IV	I	Unknown	60	18-70	N/A	Open-label	Randomized	China
12	NCT04429763	1	1 × 106/kg	N/A	II	Unknown	30	18-79	N/A	Triple-blind	Randomized	United States
13	NCT04461925	3 (at days 1,4 and 7)	1 × 106/kg	IV	I/II	Unknown	30	18-75	N/A	Open-label	Non-Randomized	Ukraine
14	NCT04269525	4 (at days 1, 3, 5 and 7)	3.3 × 107	IV	II	Unknown	16	18-80	N/A	Open-label	N/A	China
15	NCT04437823	3 (at days 1, 3, and 5)	0.5 × 106/kg	IV	II	Unknown	20	30-70	N/A	Open-label	Randomized	Pakistan
16	NCT04573270	1	N/A	IV	I	Completed	40	18 to older	N/A	Triple-blind	Randomized	United States
17	NCT05286255	2 (at days 1 and 4)	1.25-1.5 × 106/kg	IV	I	Not yet recruiting	10	18-80	N/A	Open-label	N/A	United States

UC-MSCs: Umbilical cord mesenchymal stem cells; IV: Intravenous; N/A: Not available.

Table 2 Clinical trials of umbilical cord mesenchymal stem cells therapy for patients with acute respiratory distress syndrome

No	Trial ID	UC-MSCs administration protocol			Phase	Status	Patients	Age (yr)	Follow-up time	Mask	Allocation	Country
		Frequency	Dose (cells)	Route
1	NCT05387278	3 (at days 1, 3, 5 and 7)	N/A	IV	I	Recruiting	20	18-75	12 wk	Quadruple-blind	Randomized	United States
2	NCT03608592	1	1 × 106/kg	IV	N/A	Unknown	26	18 to older	N/A	Open-label	N/A	China
3	NCT05741099	1	N/A	IV	I/II	Recruiting	20	18-85	N/A	Triple-blind	Randomized	China
4	NCT04355728	2 (within 24 h and within 72 h)	1 × 108	IV	I/II	Completed	24	18 to older	N/A	Triple-blind	Randomized	United States
5	NCT04452097	1	Group 1: 0.5 × 106/kg; group 2: 1 × 106/kg; group 3:1.5 × 106/kg	IV	I/II	Not yet recruiting	39	18-80	N/A	Open-label	Non-randomized	China
6	NCT04494386	1/2 (at days 1 or 1 and 3)	1 × 108	IV	I/II	Active, not recruiting	60	18 to older	12 months	Triple-blind	Randomized	United States
7	NCT04456361	1	1 × 108	IV	I	Active, not recruiting	9	18 to older	3 months	Open-label	N/A	Mexico
8	NCT04565665	2 (at days 1 and within 7 d)	N/A	IV	I/II	Recruiting	70	18 to older	12 months	Open-label	Randomized	United States
9	NCT03042143	1	N/A	IV	I	Recruiting	129	16 to older	N/A	Quadruple-blind	Randomized	United Kingdom
10	NCT04347967	1	N/A	IV	I	Not yet recruiting	18	20-85	N/A	Open-label	N/A	China
11	NCT04333368	3 (at days 1, 3 and 5)	1 × 106/kg	IV/CVC	I/II	Completed	40	18 to older	12 months	Triple-blind	Randomized	France
12	NCT05240430	1	1 × 106/kg	IV	N/A	Recruiting	1	18 to older	4 wk	N/A	N/A	Turkey
13	NCT04400032	3 (at days 1, 2, and 3)	Group 1: 7.5 × 107, group 2: 1.5 × 108, group 3: 2.7 × 108	IV	I/II	Completed	15	18 to older	N/A	Open-label	Non-randomized	Canada
14	NCT04490486	2 (at days 0 and 3)	1 × 108	IV	I	Withdrawn	21	18 to older	N/A	Double-blind	Randomized	United States

UC-MSCs: Umbilical cord mesenchymal stem cells; IV: Intravenous; CVC: Central venous catheter; N/A: Not available.

Table 3 Clinical trials of umbilical cord mesenchymal stem cells therapy for patients with bronchopulmonary dysplasia

No	Trial ID	UC-MSCs administration protocol			Phase	Status	Patients	Age	Follow-up time	Mask	Allocation	Country
		Frequency	Dose (cells)	Route
1	NCT04062136	2 (at days 1 and 8)	1 × 106/kg	IV	I	Unknown	10	1-6 months	N/A	Open-label	N/A	Vietnam
2	NCT02381366	1	Dose A: 1 × 107/kg; dose B: 2 × 107/kg	N/A	I/II	Completed	12	3-14 d	N/A	Open-label	N/A	United States
3	NCT03645525	1	2 × 107/kg	Endobronchial	I/II	Recruiting	180	2-3 wk	N/A	Quadruple-blind	Randomized	China
4	NCT03601416	1	Dose A: 1 × 106/kg, dose B: 5 × 106/kg	IV	II	Unknown	21	28 d to 1 yr	N/A	Open-label	Randomized	China
5	NCT03558334	1	Dose A: 1 × 106/kg, dose B: 5 × 106/kg	IV	I	Unknown	12	28 d and older	N/A	Open-label	Non-randomized	China
6	NCT01207869	1	3 × 106/kg	Endobronchial	I	Unknown	10	1 wk to 6 months	N/A	Double-blind	Randomized	China
7	NCT03873506	1	Dose A: 1 × 106/kg, dose B: 5 × 106/kg	IV	I	Unknown	30	1 months to 5 yr	N/A	Open-label	N/A	China
8	NCT03774537	1	Dose A: 1 × 106/kg, dose B: 5 × 106/kg	IV	I/II	Unknown	20	4-14 d	N/A	Open-label	Non-randomized	China
9	NCT03631420	1	Dose A: 3 × 106/kg, dose B: 1 × 107/kg, dose C: 3 × 107/kg	N/A	I	Recruiting	9	3-51 d	N/A	Open-label	N/A	China
10	NCT01632475	1	Dose A: 1 × 107/kg, dose B: 2 × 107/kg	IV	I	Active, not recruiting	9	4 months to 2 yr	N/A	Open-label	N/A	Korea
11	NCT01297205	1	Dose A: 1 × 107/kg, dose B: 2 × 107/kg	IV	I	Completed	9	5-14 d	N/A	Open-label	N/A	Korea
12	NCT04003857	1	1 × 107/kg	IV	II	Recruiting	60	6-60 months	N/A	Triple-blind	Randomized	Korea
13	NCT01897987	1	1 × 107/kg	IV	N/A	Completed	62	7 months	60 months	Triple-blind	Randomized	Korea
14	NCT01828957	1	1 × 107/kg	IV	II	Completed	69	5-14 d	N/A	Quadruple-blind	Randomized	Korea
15	NCT02023788	1	Dose A: 1 × 107/kg, dose B: 2 × 107/kg	IV	I	Completed	8	45-63 months	5 yr	Open-label	N/A	Korea
16	NCT03378063	1	N/A	N/A	I	Withdrawn	100	1-3 months	N/A	Open-label	Non-randomized	China
17	NCT03392467	1	N/A	N/A	II	Recruiting	60	Up to 13 d	N/A	Quadruple-blind	Randomized	Korea
18	NCT04255147	1	Dose A: 1 × 106/kg, dose B: 3 × 106/kg, dose C: 1 × 107/kg	IV	I	Recruiting	9	7-28 d	N/A	Open-label	N/A	Canada

UC-MSCs: Umbilical cord mesenchymal stem cells; IV: Intravenous; N/A: Not available.

Table 4 Clinical trials of umbilical cord mesenchymal stem cells therapy for patients with chronic obstructive pulmonary disease

No	Trial ID	UC-MSCs administration protocol			Phase	Status	Patients	Age (yr)	Follow-up time	Mask	Allocation	Country
		Frequency	Dose (cells)	Route
1	NCT04433104	2 (at mo 1 and 4)	1 × 106/kg	IV	II	Unknown	40	40-75	12 months	Single-blind	Non-Randomized	Vietnam
2	NCT04206007	1	N/A	IV	I	Active, not recruiting	9	40-75	48 months	Open label	N/A	China
3	NCT05147688	1	1 × 108	IV	I	Recruiting	20	Child, adult, older adult	48 months	Open-label	N/A	Antigua and Barbuda

UC-MSCs: Umbilical cord mesenchymal stem cells; IV: Intravenous; N/A: Not available.

Table 5 Clinical trials of umbilical cord mesenchymal stem cells therapy for patients with pulmonary fibrosis

No	Trial ID	UC-MSCs administration protocol			Phase	Status	Patients	Age (yr)	Follow-up time	Mask	Allocation	Country
		Frequency	Dose (cells)	Route
1	NCT05468502	1	Dose A: 6.0 × 106, dose B: 3.0 × 107, dose C: 6.0 × 107, dose D: 9.0 × 107	IV	I	Recruiting	18	50-75	N/A	Open-label	N/A	China
2	NCT02277145	1	1 × 106/kg	IV	I	Completed	10	Adult, older adult	N/A	Open-label	N/A	China
3	NCT05016817	1	1 × 108	IV	I	Recruiting	20	Child, adult, older adult	48 months	Open-label	N/A	Antigua and Barbuda, Argentina, Mexico

UC-MSCs: Umbilical cord mesenchymal stem cells; IV: Intravenous; N/A: Not available.