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. 2023 Jun 29;12(13):4385. doi: 10.3390/jcm12134385

Table 2.

Potential of MSC-EV for treatment of bone diseases on preclinical animal models.

Disease Model MSC Culture EV Isolation Application Ref.
Osteoporosis Sprague Dawley rats Rat ADMSC
Culture media not specified
48 h
Ultracentrifugation Mode: intravenous injection
EV dose (µg/µL): 0.1, 0.2, 0.5 and 1.0
[115]
C57BL/6J and 129P2-Cbstm1Unc/J (CBS KO) mice Mouse BMMSC
FBS-free medium
24 h
Ultracentrifugation Mode: intravenous injection
EV dose: 100 µg/mL
[125]
C57BL/6 mice Human UCMSC
EV-free FBS medium
48 h
Ultracentrifugation Mode: intravenous injection
EV dose: 100 μg/100 μL in PBS
[140]
C57BL/6 mice Human BMMSC
EV-free FBS medium
48 h
Ultracentrifugation Mode: intravenous injection
EV doses: 100 μL/mL
[144]
BALB/c mice Human BMMSC
FBS-free medium
48 h
Ultracentrifugation Mode: injection into the marrow cavity of femur
EV dose: 25 μg/mL
[151]
Sprague Dawley rats Rat BMMSC
transfected with miR-150-3p
FBS-free medium
24 h
exoEasy Maxi Kit Mode: intravenous injection
EV dose: 100 and 200 μg
[152]
ICR (CD-1) mice ADMSC
FBS-free medium
24 h
Multi-filtration system based on tangential flow filtration Mode: intravenous injection
EV dose: (1 × 108 or 5 × 108 particles/100 μL PBS)
[155]
Osteo-Arthritis BALB/c mice Human BMMSC and
ADMSC
FBS-free medium
48 h
Exocib Exosome Extraction Kit Mode: intravenous injection
EV dose: 100 μg/mL
[103]
Sprague Dawley rats Human ESC (E1-MYC 16.3)
FBS-free medium
72 h
high-performance liquid chromatography (HPLC) fractionation Mode: intra-articular injection
EV dose: 5 μg/mL
[108]
C57BL/6 mice Mouse BMMSC—transfection of miR- 206 culture media not specified
72 h
Ultracentrifugation Mode: intra-articular injection
EV dose: not specified
[109]
Wistar rats Human BMMSC -
EV-free FBS medium
48 h
ExoQuick-TC Re- agent Kit (EXOTC10A-1) Mode: intra-articular injection
EV dose: 400 μg/mL
[110]
Sprague Dawley rats Rat BMMSC
EV-free FBS medium 48 h
Ultracentrifugation Mode: intra-articular injection
EV dose: 2 μg
[113]
Fracture Mice Human UCMSC
Hypoxia (1% O2)
Preconditioned EV-free FBS medium
48 h
Ultracentrifugation Mode: intravenous injection
EV dose: 200 μg/200 mL in PBS
[93]
Wistar rats Human UCMSC
Culture media not specified
Ultracentrifugation Mode: intravenous injection
EV dose: 1 × 1010 particles
[132]
C57BL/6 WT mice Murine BMMSC
EV-free medium
48 h
Ultracentrifugation Mode: intravenous injection
EV dose: 100 μg
[143]
Sprague Dawley rats Rat SMC and PCCM
FBS-free medium
72 h
Ultracentrifugation Mode: intravenous injection
EV dose: 200 μg/100 μL in PBS
[161]
Critical-Sized Bone Defects C57BL/6J mice Human BMMSC
TNFα preconditioned
72 h
FBS-free medium
24 h
ExoQuick-TC Reagent (System Biosciences) Mode: collagen scaffold
EV dose: 4.5 × 109
particles
[89]
C57/BL6 mice Human BMMSC
Transfection of miR-181b
FBS-free medium
72 h
Ultracentrifugation Mode: intravenous injection
EV dose: not specified
[116]
Sprague Dawley rats Human BMMSC -DMOG preconditioned
Culture media not specified
48 h
Ultracentrifugation Mode: hydroxyapatite scaffolds
EV dose: 200 μg/100 μL in PBS
[97]
Sprague Dawley rats Human BMMSC
Culture media not specified
24 h
Ultracentrifugation Mode: hydrogel
EV dose: 5 μg/mL
[146]
Sprague Dawley rats Human PDLSC
FBS-free medium
24 h
Ultracentrifugation Mode: Matrigel matrix
EV dose: 60 µg/10 µL in PBS
[159]
Rattus sp. BMMSC- EV-free
FBS medium
48 h
Ultracentrifugation Mode: chitosan hydrogel
EV dose: 1 × 108 particles/mL
[98]
Wistar rats UMSC and HEK293 cells
Culture media and time not specified
Ultracentrifugation Mode: hyaluronic acid hydrogel, combined with nanohydroxyapatite/poly-ε-caprolactone (nHP) scaffolds
EV dose: 1 × 1012 particles/mL
[51]
BALB/C mice Human ADMSC differentiated into osteoblast-EV-free
FBS medium
0, 2, 4, 7 and 14 days
Ultracentrifugation Mode: PLGA/PDA scaffolds
EV dose: 25 µg/mL
[167]
Osteonecrosis Rabbits Rabbit BMMSC
Transfected with HIF1aMU and Adv-HIF1aWT
FBS-free medium
24 h
Total Exosomes Isolation Kit Mode: femoral-head injection
EV dose: 10 µg/mL
[131]
Sprague Dawley rats Rat BMMSC
Hypoxia (2% O2) preconditioned EV-free
FBS medium
48 h
Ultracentrifugation Mode: intravenous injection
EV dose: 50 µg/mL
[95]