Table 1.

Overview of the experiments involving the use of MSCs in MS experimental models.

Age and Strain	MS Model	MSCs	MSCs Administration	Results	Ref.
4-week-old female C57BL/6 mice	MOG-EAE	Mouse BM-MSCs	1 × 107 cells; i.p. at the disease onset (day 14) and day 20	↑ clinical score; ↓ inflammatory infiltration and demyelination of spinal cord	[23]
Adult male Swiss mice	Spinal cord homogenate EAE	Rat BM-MSCs	1 × 106; i.p. on the same day of immunization	↑ clinical score; ↓ inflammation	[24]
10–14-week-old female C57BL/6 mice	MOG-EAE	Mouse BM-MSCs	1 × 106 cells; i.p. 5 days after EAE induction	IL17/IL17RA signaling mediated the therapeutic function of MSCs in EAE	[25]
6–8-week-old female C57BL/6 mice	MOG-EAE	BM-MSCs	5 × 105 cells; i.v. at the disease onset (day 11)	↑ neurobehavioral outcomes; ↓ BBB disruption, inflammatory infiltration and demyelination in spinal cord	[26]
6–8-week-old female C57BL/6J mice	MOG-EAE	Mouse BM-MSCs	1 × 106; i.v. on the day of clinical onset	↓ vascular alteration of vessels, myelin, and neuronal damage	[27]
2-month-old female C57BL6/J mice	MOG-EAE	Human BM-MSCs	1 × 106; i.v. 7 days after EAE induction	↑ retinal ganglion cell function and motor-sensory impairment	[28]
10–14-week-old females C57BL/6 mice	MOG-EAE	Mouse BM-MSCs	1 × 106; i.v. administrated at the onset of the disease (day 10), at the peak of the disease (day 18), or at the time of EAE stabilization (day 30)	↑ clinical score; ↓ Th1, Th17, and Treg	[29]
Female C57BL/6 mice	MOG-EAE and cuprizone model	Mouse BM-MSCs	5 × 106 cells; EAE: i.p. on day 3 and 8. Cuprizone: i.p. weekly	↓ Th17 activation and function; positive effects only in cuprizone model	[30]
6-week-old male C57BL/6 mice	Cuprizone model	Mouse BM-MSCs	3 × 105 cells; lateral ventricle after cuprizone treatment	↑ M2 phenotype; ↓ M1 phenotype	[31]
8-week-old male C57BL/6 mice	Cuprizone model	Mouse BM-MSCs	3 × 105 cells; lateral ventricle after 12 weeks of diet with cuprizone	↑ remyelination; ↓ microgliosis and astrocytosis	[32]
7–8-week-old male C57BL/6 mice	Cuprizone model	Human BM-MSCs	2 × 106 cells for 2 consecutive weeks i.p. after 4 weeks of cuprizone treatment	↓ demyelination in corpus callosum	[33]
7–8-week-old male C57BL/6 mice	Cuprizone model	Mouse BM-MSCs	1 × 106; i.v. 2 weeks after cuprizone diet	↑ remyelination; ↓ demyelination and apoptosis	[34]
12-month-old male Fischer 344 rats	Ethidium bromide	Rat BM-MSCs (2-month-old and 17–20-month-old rat donors)	1.5–2.0 × 106 MSCs; i.v. at 1, 2, and 3 days post-lesion induction	↑ differentiation of OPC with young MSCs	[35]
6–8-week-old female C57BL/6 mice	MOG-EAE	Mouse AD-MSCs expanded in hypoxia or human AD-MSCs	1 × 106 cells; i.p. at the disease onset or at the acute phase	↓ disease severity, inflammatory cell infiltration, and demyelination	[36]
Dogs	Demyelinating leukoencephalitis caused by the distemper virus	Canine AD-MSCs	1 × 107; 3 doses into the femoral artery at 30-day intervals	↓ myoclonus	[37]
6–8-week-old female C57Bl/6 mice	MOG-EAE	Human AD-MSCs	1 × 106; i.p. before disease onset or at the peak of disease severity	Obese derived AD-MSCs failed to improve EAE	[38]
6–8-week-old female C57Bl/6 mice	MOG-EAE	Mouse AD-MSCs	1 × 106; i.p. 20 days after immunization	↑ clinical score, behavior, motor function, and histopathologic analyses	[39]
6–8-week-old female C57Bl/6 mice	MOG-EAE	Mouse AD-MSCs	1 × 106; i.p. 8 days after immunization	↑ SVF cells and AD-MSCs administration transiently increased disease severity. SVF cells were able to overcome the advancing pathogenesis and showed improvements	[40]
12-week-old male C57BL/6 mice	MOG-EAE	Human PDLSCs	1 × 106 cells; i.v. at the disease onset (day 14)	↑ clinical score, lymphocytic infiltration and demyelination; ↓ apoptosis	[41]
6–8-week-old C57BL/6J mice	MOG-EAE	Mouse S-MSCs	1 × 106; i.p. 3 days before immunization or on day 8 post immunization	↑ expression of Th2- and Treg-associated genes; ↓ disease onset, disease severity, demyelination, inflammatory cell infiltrate, Th17 cell induction	[42]
8-week-old male C57BL/6 mice	Cuprizone model	Human WJ-MSCs	3 × 105 cells; lateral ventricle after 12 weeks of diet with cuprizone	↑ remyelination and oligodendrocyte; ↓ astrogliosis, microgliosis, oxidative stress, and mitochondrial dysfunction	[43]
8-week-old female dark agouti rats	MOG-EAE	Human WJ-MSCs	2 × 106; i.v. at the onset of clinical symptoms. In order to assess the effect on chronic disease course, rats received a dose at 28 days post immunization	↑ improved clinical score in EAE rats; ↓ proliferation of activated T	[44]
3–5-year-old cynomolgus monkeys	MOG-EAE	Human UCMSCs	1 × 106 cells/kg/mL; i.v. at days 74 and 84	↓ demyelination and inflammation	[45]
8–10-week-old female C57BL/6 mice	MOG-EAE	Human AMCs	1 × 106 cells; i.p. at the disease onset (day 14)	↑ remyelination and neurotrophic factors; ↓ clinical score, inflammation	[46]
6–8-week-old female Wistar rats	MOG-EAE	Human PMSCs	1 × 106 cells; i.v. at 9 or 16 days post immunization	↑ oligodendrocyte precursors; ↓ inflammation, axonal injury and degenerating neurons	[47]
9–10-week-old male Lewis rats	Spinal cord homogenate EAE	Rat PMSCs; EMSCs	1 × 106 cells; ICV 10 days after EAE induction	↑ neurological functions; ↓ infiltrating inflammatory cells, gliosis, apoptosis, and demyelination	[48]
8–9-year-old female cynomolgus monkeys	MOG-EAE	EMSCs	2 × 107 cells/monkey; i.t. 3 doses	↓ clinical symptoms, brain lesion, and demyelination	[49]
10–14-week-old female C57BL/6 mice	MOG-EAE	Human DMSCs	1 × 106 cells; i.p. at days 1, 3 and 6, or days 6-10 after MOG inoculation.	↓ demyelination and inflammatory cell infiltration	[50]
Female C57BL/6J mice	MOG-EAE	Mouse BM-MSCs	1 × 106 cells; i.v. at the disease onset (day 11) or at day 3 and 8	No improvements in EAE	[51]
10-week-old male C57BL/6J mice	Cuprizone model	Human and murine BM-MSCs; canine AD-MSCs	1 × 106 cells; intraventricularly or intralesion at week 3 or week 4	No regenerative effects	[52]
12-week-old male C57BL/6 mice	MOG-EAE	Mouse BM-MSCs	1 × 106; i.v. 8 days after immunization	Superior effects of mMAPCs compared to MSCs	[53]
10–12-week-old female C57BL/6 mice	MOG-EAE	EAE or naïve mouse BM-MSCs; human BM-MSCs obtained from RRMS or control subjects	0.8 × 106; i.v. 15 days post immunization	BM-MSCs obtained from EAE mice did not improve EAE	[54]

AD-MSCs, Adipose tissue-derived MSCs; AMC, amnion mesenchymal cells; BBB, blood-brain barrier; BM-MSCs, Bone marrow MSCs; DMSCs, Decidua derived MSCs; EAE, experimental autoimmune encephalomyelitis; EMCSs, Embryonic MSCs; IL, interleukin; i.p. intraperitoneal; i.v. intravenous; IL17RA, IL17 Receptor A; mMAPCs, Mouse multipotent adult progenitor cells; MOG, myelin oligodendrocyte glycoprotein; MSCs, mesenchymal stem cells; OPC, Oligodendrocyte progenitor cell; PMSCs, Placental derived MSCs; SVF, Stromal vascular fraction; Th, T helper; Treg, regulatory T; UCMSCs, Umbilical cord MSCs; WJ-MSCs, Wharton’s jelly-derived MSCs. ↑, enhancement; ↓, reduction.