Table 1.

Comparison between MSCs and MSC-EVs

Characteristic	MSCs	MSC-EVs	Notes	References
Determination of HSC fate	Yes	Similar to MSCs	Both MSCs and MSC-EVs have the proliferation and differentiation capacity of HSCs in vivo and in vitro, as well as inhibition of HSC apoptosis	[62, 73–75]
Malignant transformation	Yes/no	Not reported	Malignant transformation of MSCs depend on source, passage number, expansion protocol, medium conditions, etc	[91–96, 102]
Bone regeneration	Yes	Similar to MSCs	MSCs engaged in bone regeneration via differentiation to osteoblasts, MSC-EVs promote bone regeneration via microRNAs, especially miR-335	[3, 89–91]
Genetically instability	Possible	Not reported	Chromosomal anomalies in MSCs were seen at higher passages	[101]
Ectopic differentiation	Yes	Not reported	Bone formation in ectopic tissues after systemic infusion of MSCs were seen but not in MSC-EVs injection	[99, 100]
Opportunistic infections	High risk	Safe	MSCs are good vectors for microorganisms such as B19, CMV, HSV-1, and Mycoplasma hyorhinis but not reported for MSC-EVs	[85–87]
Immunosuppressive potency	Potent	Low potent	Increase recipient susceptibility to opportunistic infections	[3, 20, 21]
Risk of GVHD	Low Risk	Less than MSCs	Due to altering the proportion of immune cells, increasing the production of anti-inflammatory cytokines and decrease pro-inflammatory cytokine release	[64, 110]
Potential of tumor promoting effects	Dual role	Similar to MSCs	It depends on balance between inhibitory (e.g., miR-221, -23b, -1587) and promotional (e.g., miR-145, -124a, -16) bioactive molecules	[96–98]

MSCs: Mesenchymal stem cells; MSC-EVs: Mesenchymal stem cell-derived extracellular vesicles; HSC: Hematopoietic stem cell; miR: microRNA; GVHD: graft-versus-host disease; B19: Parvovirus B19; CMV: Cytomegalovirus; HSV-1: Herpes Simplex