Table 1.

Effects of MSC preconditioning on EV cargos and responses during bone remodeling.

MSC Preconditioning	Conditions	Cargo	Response	References
TUDCA	2.5 µM	↑ Anti-inflammatory cytokines (IL1RN, IL6, IL10 and IL11) ↑ Anti-inflammatory miRNA (miR-145-5p) ↓ Inflammatory miRNA (miR-423-3p) ↑ Osteogenic factors (ALP, RUNX2, BMP2 and BMPR) ↓ Anti- osteogenic miRNA (miR-206) ↑ Osteogenic miRNA (miR-136-5)	Improve bone-tissue regeneration	[87,88]
Inflammatory cytokines TNF-α	72 h 20 ng	↑ Anti-inflammatory miRNA (miR-15b, miR-19b and miR-22)	M1 macrophage polarization into M2 Produce greater bone formation and reduce inflammation	[89]
	–	↑ CD73 and miR-1260b ↓ WNT5a expression and RANKL	M1 macrophage polarization into M2 Reduce inflammation and osteoclastogenesis	[90]
	72 h 1 ng/mL	↑ WNT-3A protein	Greater osteogenic proliferation and differentiation	[91]
PTH 1-34	6 h + 48 h before isolation	↓ Inflammatory factors (IL-2, TNF-α and IL-6)	Increase proliferation, migration and extracellular-matrix production	[92]
Hypoxia	1% O2 48 h	↑ Angiogenic miRNA (miR-126 and miR-210-3p)	Greater angiogenic capacity Accelerate bone-fracture healing M1 macrophage polarization into M2 Inhibition of osteoclastogenesis	[93,94]
	2% O2 48 h	↑ Angiogenic miRNA (miR-210-3p)	Angiogenesis stimulation Improve osteonecrosis of femoral head	[95]
DMOG	-	-	Greater angiogenic capacity Bone regeneration	[96,97]
Fe3O4 nanoparticles	Combination with static magnetic field	↑ Osteogenic miRNA (miR-1260a)	Promote osteogenesis and angiogenesis	[98]
BGN	48 h	↑ (NFAT; NROM) lncRNA	Inhibition of osteoclastogenesis	[99]
Osteoblast differentiation	Osteogenic medium 48 h	-	Enhance differentiation of osteoblast cultures Lower proliferation capacity	[100]
	Osteogenic medium 72 h	-	Higher recruitment of MSC Immunomodulatory properties Improve bone formation	[86]