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. Author manuscript; available in PMC: 2023 Mar 1.
Published in final edited form as: Adv Healthc Mater. 2021 Jul 23;11(5):e2100596. doi: 10.1002/adhm.202100596

Table 2:

Experimental Parameters and Configuration of Preclinical Studies.

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