Table 5.

Overview of the experiments involving the use of MSC secretome in MS experimental models.

Age and Strain	MS Model	MSCs Source	Secretome	Administration	Results	Ref.
Female C57BL/6 mice	MOG-EAE	Mouse BM-MSCs	CM	60 μL/mouse (30 μL on each nostril); i.n. from the day 3 after immunization until the onset of symptoms	↓ disease onset and disease severity demyelination B cells infiltration and microglia activation	[74]
8-week-old female C57BL/6J mice	MOG-EAE	SHED	CM	500 µl; i.v. 14 days after immunization corresponding to the peak of EAE	↑ clinical scores; ↓ demyelination, axonal injury, inflammatory infiltrates, and the expression of proinflammatory cytokines	[75]
6–7-week-old female C57BL/6 mice	MOG-EAE	Mouse AD-MSCs	CM	1 mL; i.p. on day 10 after immunization and the same amount once a week for four weeks. 1 × 106 AD-MSCs i.p.	↑ clinical scores; ↓ inflammatory infiltration	[76]
6–7-week-old female C57BL/6 mice	MOG-EAE	Human PDLSCs	CM obtained in hypoxic condition	1.0 mg/mouse; i.v. after 14 days from EAE induction	↑ IL-37 and BDNF levels; ↓ inflammatory cell infiltration, demyelination, oxidative stress, and apoptosis	[77]
12-week-old male C57BL/6 mice	MOG-EAE	Human PDLSCs derived from RRMS patients and healthy controls	CM and EMVs	1600 μG for CM or 24 μG for EMVs; i.v. after 14 days of EAE induction	↓ inflammasome, NF-κB and inflammatory cell infiltration	[78]
10-week-old male C57BL/6 mice	MOG-EAE	Human WJ-MSCs differentiated toward oligodendrocytes	CM	i.n. 10 days after immunization	↑ remyelination and neurological scores; ↓ inflammatory cell infiltration and the expression of proinflammatory markers	[79]
4–6-week-old female SJL/J mice	TMEV-induced demyelinating disease	Human AD-MSCs	EVs	25 μg; i.v. on day 60 post infection	↑ motor function; ↓ brain atrophy, inflammatory infiltration and plasma cytokine levels	[80]
6–8-week-old female C57Bl/6 mice	MOG-EAE	Human AD-MSCs	EVs	60 μg EVs or 1 × 106 AD-MSC; i.v. 10 days after immunization	↑ clinical score; ↓ inflammatory infiltrates and demyelination	[81]
3-month-old male and female C57BL/6J mice	MOG-EAE	Human PMSCs	EVs	1 × 107 (low dose), 1 × 1010 (high dose) EVs, 1 × 106 PMSCs; i.v. on day 19 (peak of the disease)	↑ motor function, myelination	[82]
6–8-week-old female C57BL/6J mice	MOG-EAE	Human BM-MSCs	Exo	150 μg or 1 × 106 native or IFN-γ stimulated MSCs; i.v. at the peak of the disease (day 18)	↑ Tregs; ↓ demyelination and neuroinflammation	[83]
Female Sprague Dawley rats	Spinal cord homogenate EAE	Rat BM-MSCs	Exo	100 μg or 400 µg; i.v. the day after EAE induction. 1 × 106 BM-MSCs	↑ M2-related markers and behavioral scores; ↓ demyelination and inflammatory cell infiltration	[84]
10–13-week-old female C57BL/6 mice	MOG-EAE	Mouse BM-MSCs	Exo	200 μg of Exo or Exo-APT; i.v. on day 1, 3, 6 after immunization in the prophylactic model or on day 12, 15, and 18 in the therapeutic model	↓ disease severity, inflammation, and demyelination	[85]

AD-MSCs, Adipose tissue-derived MSCs; BM-MSCs, Bone marrow MSCs; CM, conditioned medium; EAE, experimental autoimmune encephalomyelitis; EVs, Extracellular vesicles; Exo, exosomes; IFN, interferon; i.p., intraperitoneal; i.v., intravenous; MOG, myelin oligodendrocyte glycoprotein; MSCs, mesenchymal stem cells; PDLSCs, Periodontal Ligament Stem Cells; PMSCs, Placental derived MSCs; RRMS, relapsing remitting multiple sclerosis; SHED, stem cells from human exfoliated deciduous teeth; TMEV, Theiler’s murine encephalomyelitis virus; Treg, Regulatory T. ↑, enhancement; ↓, reduction.