. 2022 Feb 15;28(1):101–113. doi: 10.1089/ten.teb.2020.0246

Table 1.

Mesenchymal Stem Cell-Derived Exosomes in Bone Regeneration

Parent cells	Target cells	Isolation	Characterization	Preconditioning of parent cells	In vitro	Animal models	In vivo
hBMSCs^58–64 mBMSCs⁶⁵ rBMSCs^66–71,75 hBMSCs from the jaw⁷² Rabbit BMSCs⁷³ hBMSCs from traumatic ONFH patients⁷⁴	hBMSCs^{58,59,62,64,72} mBMSCs (MRL/lpr)⁶⁵ Human osteoblasts^60,75 mouse Osteoblasts⁷⁰ BMSCs from SFHN rat⁶⁶ rBMSCs^67,69 irradiated rBMSCs⁷¹ hUVECs^63,70,74	ExoQuick-TC^58,59,62,66 UC^{60,61,63–65,68–73,75} Total Exosome Isolation Kit^67,74 UF^69,70	TEM^{58,60,62–64,66–74} DLS^59,69 Atomic force microscopy⁵⁹ Laser Doppler micro-electrophoresis⁵⁹ Flow cytometry^59,60,69 WB^{61–67,70–74} FTE⁶¹ NTA^{62–64,67,69,70,72–74} TRPS⁶⁸	Osteogenic induction^58,59,62 HIF-1α-adenovirus transfection⁶⁷ Dimethyloxaloylglycine-stimulation⁶³ miR-122-5p transfection⁷³	Increased expression of osteogenic proteins/genes^{58–60,62,64–69,72} Increased mineralization^{60,64,66–70,72} Decreased adipogenesis⁶⁶ Increased angiogenesis^63,64,70,74 Increased proliferation^68,70,75 Increased migration⁷⁰ Reduced oxidative stress, accelerated DNA repair, attenuated inhibition of proliferation, and osteogenic differentiation potential in irradiated BMSCs⁷¹	Implantation in the back of immunocompromised mice^58,62 IV injection in a mouse model of SLE⁶⁵ Calvarial bone defect in rats^60,63,64and mice⁷² Femur fracture in mice ⁶¹ and rats^69,70 ONFH model in rats^67,74 and rabbits⁷³ Tibial distraction model in rats⁶⁸ Radiation-induced bone loss in rats⁷¹	Increased vascularization^{58,63,64,70,73,74} Increased bone formation^{58,60,61,63–74} Increased expression of osteogenic proteins/genes^{58,62,65,69,70} Increased expression of angiogenic proteins/genes^58,70 Reduced oxidative stress⁷¹ Prevention of bone mineral loss^67,73,74
hASCs^76,77	hBMSC^76,77	UF⁷⁶ UC^76,77	TEM^76,77 NTA^76,77 WB^76,77	Osteogenic differentiation⁷⁶ miR-375 lentiviral transfection⁷⁷	Increased proliferation⁷⁶ Increased migration⁷⁶ Increased mineralization⁷⁶ Increased expression of osteogenic proteins/genes⁷⁶	Calvarial bone defects in mice⁷⁶ and rats⁷⁷	Increased bone formation^76,77 Increased expression of osteogenic proteins/genes⁷⁶
Synovial-derived MSCs⁷⁸	hBMSCs Treated and untreated with steroids⁷⁸	UF⁷⁸ UC⁷⁸	DLS⁷⁸ TEM⁷⁸ WB⁷⁸		Increased proliferation in untreated BMSCs⁷⁸ Inhibition of decreased proliferation of steroid treated BMSCs⁷⁸ Inhibition of apoptotic effects⁷⁸	ONFH model in rats⁷⁸	Prevention of bone mineral loss and cystic degeneration⁷⁸ Increased bone formation⁷⁸
hiPSC-MSCs^79–81	rBMSC-OVX⁸⁰ hBMSCs⁸¹ hUVECs⁷⁹	UF^80,81 UC^79–81	TRPS^80,81 WB^79–81 TEM^79,81 NTA⁷⁹		Increased proliferation^79–81 Increased mineralization^80,81 Increased expression of osteogenic proteins/genes^80,81 Increased migration⁷⁹ Increased tube formation⁷⁹	Calvarial bone defects in OVX rats⁸⁰ and rats⁸¹ ONFH model in rats⁷⁹	Increased bone formation^80,81 Increased expression of osteogenic proteins/genes^80,81 Increased vascularization^79,80 Increased expression of angiogenic proteins/genes⁸⁰ Prevention of bone mineral loss⁷⁹
human Wharton's jelly of umbilical cord MSCs⁸²	Mouse osteocyte-like cells treated with steroids⁸²	exoEasy Maxi Kit⁸²	TEM⁸² DLS⁸² WB⁸²		Inhibition of decreased proliferation of steroid-treated cells⁸² Inhibition of apoptotic effects⁸²	ONFH model in rats⁸²	Prevention of bone mineral loss⁸²
hucMSCs^83–87	hUVECs^83,84 human Osteoblasts⁸³ mouse Osteoblasts⁸⁴ rBMSCs from DOP model⁸⁷	UC^83–87 UF^83,84,86	TEM^83–87 WB^83–87 NTA^83,87 DLS⁸⁴	Hypoxic conditions⁸³	Increased expression of angiogenic proteins/genes^83,84 Increased proliferation^83,84 Increased migration^83,84 Increased tube formation^83,84 Inhibition of decreased proliferation in DOP⁸⁷ Inhibition of apoptotic effects in DOP⁸⁷	ONFH model in rats⁸⁵ Femur fracture in mice⁸³ and rats^84,86 DOP model in rats⁸⁷	Increased bone formation^83–87 Inhibition of apoptotic effects^85,87 Increased vascularization^84,85 Increased expression of osteogenic proteins/genes⁸⁶
hMSCs⁵¹	hMSCs⁵¹	UC⁵¹ UF⁵¹	TEM⁵¹ NTA⁵¹	Osteogenic induction⁵¹	Increased mineralization⁵¹

ASC, adipose tissue-derived MSC; BMSC, bone marrow stem cell; DLS, dynamic light scattering; DOP, disuse osteoporosis; FTE, high-resolution frequency transmission electric-field imaging; h, human; HIF-1α, hypoxia-inducible factor-1 alpha; hiPSC, human induced pluripotent stem cell; hucMSC, human umbilical cord-derived MSC; hUVEC, human umbilical vein endothelial cell; IV, intravenous; m mouse; MRL, Murphy Roths Large; MSC, mesenchymal stem cell; NTA, nanoparticle tracking analysis; ONFH osteonecrosis of the femoral head; OVX, ovariectomy; r, rat; SLE, systemic lupus erythematosus; TEM, transmission electron microscopy; TRPS, tunable resistive pulse sensing; UC, ultracentrifugation; UF, ultrafiltration; WB, western blot.