Table 2:
Reference | Cell Source of EV | Species of Cell Source | Cell Source Culture Conditions | Test Method of Application | Species of Target Cell or Tissue | Dosage of EVs Used* | Target Cell Type or Tissue | Biochemical Challenge? | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AF | NP | non-CEPCs | CEPCs | MSC | Intradiscal Injection (Whole IVD) | Dorsal Nerve Root | Other | ||||||||
Xia et al., 2019[99] | BM-MSCs | Mouse | Normoxic | in vitro | Rat | 100 μg/mL | X | H2O2 (500μM) | |||||||
in vivo | X (L4/5) | ||||||||||||||
Lu et al., 2017[100] | BM-MSCs | Human | Normoxic | in vitro | Human | 50μg/mL | X | No | |||||||
NPCs | Human | Normoxic | in vitro | Human | 1, 10, 100 μg/mL | X | |||||||||
Bach et al., 2017[101] | NCs | Porcine | Hypoxic (5% O2) | in vitro | Canine | 1:1, 1:2, 1:4, 1:8, 1:16 | X | No | |||||||
Human | X | ||||||||||||||
Lan et al., 2019[102] | NPCs | Rat | Normoxic | in vitro | Rat | 0, 25, 50, 75, 100 μg/mL | X | No | |||||||
Qi et al., 2019[103] | UC-MSCs | Human | Normoxic | in vitro | Human | N/A | X | High Glucose (35mM) | |||||||
Cheng et al., 2018[104] | BM-MSCs | Human | Normoxic | in vitro | Rat | 1μg/mL | X | TNFα (5ng/mL) | |||||||
in vivo | 1.5×106 particles/2 μL | X (Co6/7, Co8/9, Co 10/11) | No | ||||||||||||
Yuan et al., 2019[105] | CEPCs | Rat | Not Specified | in vitro | Rat | 1 μg/mL | X | H2O2 (1–2mM) | |||||||
Moen et al., 2017[106] | NPCs | Rat | Normoxic | in vivo | Rat | N/A | X | No | |||||||
Bach et al., 2016[107] | NCs | Porcine | Hypoxic (5% O2) | in vitro | Bovine | N/A | X | No | |||||||
Canine | Canine | 1X, 10X | X | No | |||||||||||
Bari et al., 2018[108] | ASCs | Human | Normoxic | in vitro | Human | 5, 12.5, 25, 50, 75, 100, 150, 200 mg/mL | X | X | Fibroblasts | H2O2 (1mM) | |||||
Liao et al., 2019[109] | BM-MSCs | Human | Not Specified | in vitro | Human | 10, 50, 100 μg/mL | X | AGEs (200μg/mL) | |||||||
in vivo | Rat | 100 μg/mL | X (Co7/8, Co8/9, Co 9/10) | ||||||||||||
Chen et al., 2020[110] | NPCs | Rat | Normoxic | in vitro | Rat | Not Specified | X | IL-1β (10ng/mL) | |||||||
Hingert et al., 2020[111] | BM-MSCs | Human | Normoxic | in vitro | Human | 5×1010 particles/mL | X | X | No | ||||||
Hu et al., 2020[112] | NPCs | Rat | Normoxic | in vitro | N/A | N/A | Rapamycin (100nM) | ||||||||
Li et al., 2020[113] | BM-MSCs | Human | Normoxic | in vitro | Human | 1, 5, 10, 15, 20, 25, 30 μg/mL | X | HCl pH(Medium) = 6.5–6.7 & 5.9–6.1 | |||||||
Li et al., 2020[114] | BM-MSCs | Human | Normoxic | in vitro | Human | Not Specified | X | IL-1β (10ng/mL) | |||||||
Luo et al., 2021[115] | CESCs | Rat | Normoxic | in vitro | Rat | 40μg/mL | X | TBHP (100μmol/mL) | |||||||
in vivo | X (Levels not specified) | LY294002 (20μmol/mL) | |||||||||||||
Song et al., 2020[116] | NPCs | Human | Normoxic | in vitro | Human | Not Specified | X | No | |||||||
in vivo | Rat | X (Co5/6, Co6/7, Co7/8) | |||||||||||||
Sun et al., 2020[117] | NCs | Rat | Normoxic | in vitro | Human | 0, 50, 100, 150 μg | HUVEC | No | |||||||
in vivo | Mouse | Not Specified | X (C4/5) | ||||||||||||
Sun et al., 2021[118] | AFCs | Human | Normoxic | in vitro | Human | 100μg/mL | HUVEC | No | |||||||
Tang et al., 2021[119] | NPCs | Human | Normoxic | in vitro | Human | 1×109 particles/mL | X | No | |||||||
PMEFs | Mouse | in vivo | Mouse | 2.6×108 particles/2μL | X (L4/5, L5/6, L6/S1) | ||||||||||
Wen et al., 2021[120] | BM-MSCs | Rat | Normoxic | in vitro | Mouse | 20μM | X | No | |||||||
in vivo | 100μg/mL | X (L2/3, L3/4, L4/5) | |||||||||||||
Xiang et al., 2020[121] | USCs | Human | Normoxic | in vitro | Human | 10, 50, 100 μg/mL | X | 1.0MPa – 90% N2, 5% CO2, 5% O2 | |||||||
in vivo | Rat | 100μg/mL | X (Co4/5) | No | |||||||||||
Xie et al., 2020[122] | MSCs | Rat | Normoxic | in vitro | Rat | Not Specified | X | TBHP (20–60μM) | |||||||
in vivo | X (Co7/8) | No | |||||||||||||
Yuan et al., 2020[123] | PLMSCs | Human | Normoxic | in vitro | Human | 1×1010 particles/mL | X | TNFα (10ng/mL) | |||||||
in vivo | Mouse | X (L5/6, L6/S1) | No | ||||||||||||
Zhang et al., 2020[124] | MSCs | Human | Normoxic | in vitro | Mouse | 20μg/mL | X | LPS (5mmol/L) | |||||||
in vivo | X (Levels not specified) | No | |||||||||||||
Zhang et al., 2020[125] | NPCs | Rat | Normoxic | in vitro | Rat | Not Specified | X | IL-1β (Concentration not specified) | |||||||
Zhu et al., 2020[126] | BM-MSCs | Mouse | Normoxic | in vitro | Mouse | 50μg/mL | X | IL-1β (10ng/mL) | |||||||
Zhu et al., 2020[127] | BM-MSCs | Rat | Normoxic | in vitro | Rat | Not Specified | X | TNFα (20ng/mL) |
MSC = Mesenchymal Stem Cell; BM-MSC = Bone Marrow-derived Mesenchymal Stem Cell; NPC = Nucleus Pulposus Cell; NC = Notochordal Cell; AFC = Annulus Fibrosus Cell; UC-MSC = Umbilical Cord-derived Mesenchymal Stem Cell; ASC = Adipose-derived Mesenchymal Stromal Cell; CEPC = Cartilage Endplate Chondrocyte; CESC = Cartilage Endplate Stem Cell; PMEF = Primary Mouse Embryonic Fibroblast; USC = Urine-derived Stem Cell; PLMSC = Placental Mesenchymal Stem Cell; HUVEC = Human Umbilical Vein Endothelial Cell;
Bold = EV concentration that elicited the strongest effect sizes in downstream cellular and/or tissue responses