Table 4.

Clinical trials using mesenchymal stem cells in MS patients

Source of cells	Years	Country	Phase	NCT number	Type of study	MS type	n	EDSS	Route of administ	Dose of MSCss	Number of administrations	Immunological findings	Ref
aMSCs	2013	Italy	I/II	NCT01854957	Randomized, double-blind, placebo-compared	Active PPMS, SPMS, RRMS	185	2.5–6.5	i.v.	A dose of 1–2 × 106 MSCs/kg body weight	Single	Unreported	142
aMSCs	2013–2016	UK	I/II	NCT01606215
aMSCs	2014–2018	Canada	II	NCT02239393
aBM-MSCs	2015–2018	France	I/II	NCT02403947
aBM-MSCs	2013–2016	Spain	I/II	NCT02035514
aADMSCs	2012–2015	Sweden	I/II	NCT01730547
aMSCs	2011–2018	Iran	I/II	NCT01377870	Randomized, double-blind, placebo-compared	RRMS, SPMS, RRMS	22	3–6.5	i.v.	Unreported	Single	Unreported	Unpublished
aMSCs	2010–2014	Spain	II	NCT01228266	Randomized, double-blind, placebo-controlled, crossover	RRMS	9	3–6.5	i.v	A dose of 1–2 × 106 MSCs/kg body weight	Single	Non significative decrease of Th1 and Th17 cells; increase of Breg	143
aMSCs	2011–2016	USA	I	NCT00813969	Open-label	RRMS, SPMS	24	3–6.5	i.v.	A dose of 2 × 106 MSCs/kg body weight	Single	Unreported	144
aBM-MSCs	2014–2016	Israel	II	NCT02166021	Randomized, double-blind, placebo-compared	PPMS, SPMS	48	3.5–6.5	i.t. and i.v.	10 × 106/mL to 15 × 106/mL	Double	Unreported	Unpublished
aBM-MSCs	2006–2011	UK	I/II	NCT00395200	Open-label	SPMS	10	2–6.5	i.v.	A dose of 2 × 106 MSCs/kg body weight	Single	Unreported	145,146
aBM-MSCs	2013–2017	Jordan	II	NCT01895439	Open-label	MS	13	≤6	i.t.	Unreported	Unreported	Unreported	Unpublished
aBM-MSCs	2006–2009	Israel	I/II	NCT00781872	Open-safety clinical trial	Active MS and ALS	15 MS and 19 ALS	4–8	i.t. and i.v.	60 × 106 i.t. (n = 34) and 25 × 106 i.v. (n = 14)	Single	Increase of Treg (CD4+ CD25+) and decrease of CD83+ and CD86+ on DC and activated CD40+ cells. Decrease of in vitro lymphocytes proliferation to PHA	147
aBM-MSCs	2017	Jordan	I	NCT03069170	Open-label	RRMS	50	3–6.5	i.t. and i.v.	Unreported	Single	Recruiting IgG, IgA, and IgM levels and complement factors C3 and C4 will be analysed	Unpublished
aBM-MSCs	2015–2017	India	I/II	NCT02418351	Open-label	RRMS	69	3.5–6.5	i.t. and i.v.	50 × 106 BM-MNC (i.v.) and 100 × 106 BM-MNCs i.t. (when associated with CCSVI)	Single	Unreported	Unpublished
alloUCMSCs	2015–2017	Trinidad and Tobago	I/II	NCT02418325	Open-label	RRMS	69	3.5–6.5	i.t. and i.v.	50 × 106 UC-MSCs (i.v.) and 100 × 106 UC-MSCs i.t. (when associated with CCSVI)	Single	Unreported	Unpublished
aBM-MSCs	2015–2018	Spain	I/II	NCT02495766	Quadruple-blind, placebo-controlled study	RRMS and SPMS	8	<6.5	i.v.	Unreported	Single	Unreported	Unpublished
aBM-MSCs	2014–2018	UK	II	NCT01815632	Double-blind, placebo-controlled study	SPMS and PPMS	80	4–6	i.v.	500–600 mL bone marrow	single	Unreported	148
aBM-MSCs	2013–2018	UK	II	NCT01932593	Double-blind, placebo-controlled study	SPMS and PPMS	6	4–6	i.v.	500–600 mL bone marrow	Reinfusion (extension of NCT01815632)	Unreported	149
aADMSCs	2010–2015	Spain	I/II	NCT01056471	Triple-blind, placebo-controlled study	SPMS	30 [11 placebo, 10 low-dose and 9 high-dose]	5.5–9	i.v.	Low-dose (1 × 106 cells/kg) or high-dose (4 × 106 cells/kg)	Single	Unreported	150
aADMSCs	2014–2018	German	I	NCT02326935	Open-label	MS patients	2	Unreported	i.v.	150 × 106 cells	Single	Unreported	Unpublished
aASVF	2014–2018	USA	II	NCT02157064	Open-label	MS patients	221	Unreported	Unreported	Unreported	Unreported	Unreported	Unpublished
alloUCMSCs	2014–2017	Panama	I/II	NCT02034188	Open-label	MS patients	20	2–5.5	i.v.	Infusions of 20 × 106 UCMSCs over 7 days	7 doses	Unreported	151
alloUCMSCs	2010–2014	China	I/II	NCT01364246	Open-label	Progressive MS and NMO	20	Unreported	Unreported	Unreported	Unreported	Unreported	Unpublished
alloUCMSCs	2017	Jordan	I/II	NCT03326505	Randomized, single-blind	MS patients	60	≤7	i.t.	Unreported	Single	Unreported	Unpublished

aADMSCs autologous adipose-derived MSCs, aASVF autologous adipose stromal vascular fraction, aBM-MSCs autologous bone marrow-derived MSCs, alloUCMSCs allogenic umbilical cord-derived MSCs, ALS amyotrophic lateral sclerosis, aMSCs autologous MSCs, i.v. intravenous, i.t. intrathecal, MS multiple sclerosis, MSCs mesenchymal stem cells, PPMS primary-progressive MS, RRMS relapsing-remitting MS, SPMS secondary-progressive MS