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Table 1 Summary of selected studies characteristics

From: Mesenchymal stromal cells-derived extracellular vesicles in cartilage regeneration: potential and limitations

Ref.

Year

Country

Producing cells

Cell culture conditions

sEVs isolation method

Yield

Type of study

Medium

Type

Duration

Stimuli

[13]

2024

China

ADSCs (human)

MSC Medium

5% EV-free FBS

2D/3D

48 h

Gelatin methacryloyl

scaffolds (3D)

Differential ultracentrifugation

2–3 µg/ml (2D)

10–15 µg/ml (3D)

In vitro

[17]

2023

Japan

ADSCs (human)

CMDs

(serum-free)

2D

48 h

-

Filter concentration of filtered supernatant

5 × 108 EVs/ml

50 µg/ml

In vitro, in vivo

[49]

2023

USA

ADSCs (human)

MSC Growth/

DMEM/hPL

(EV-free)

2D

-

hPL

Differential ultracentrifugation

3–4 × 109 EVs/ml

In vivo

[51]

2022

Canada

ADSCs (human)

CDM (PPRF-msc6)

(serum-free)

2D/3D

72–84 h

Shaking (3D)

Differential ultracentrifugation

3 × 108 EVs/ml

1.5 × 103 EVs/cell

In vivo

[46]

2021

Italy

ADSCs (human)

α-MEM

serum-free

2D

48 h

IL-1β (1 ng/ml)

Differential ultracentrifugation

-

In vitro

[24]

2021

Spain

ADSCs (human)

DMEM/F12

15% EV-free

human serum

2D

48 h

-

Differential ultracentrifugation

-

In vitro

[19]

2020

Italy

ADSCs (human)

DMEM

serum-free

2D

72 h

-

Differential ultracentrifugation

2.6 × 102 EVs/cell

1.36 µg/106 cells

In vitro

[14]

2020

Italy

ADSCs (human)

DMEM

serum-free

2D

48 h

-

Differential ultracentrifugation

-

In vitro

[15]

2020

Italy

ADSCs (human)

DMEM

serum-free

2D

48 h

-

Differential ultracentrifugation

-

In vitro

[31]

2020

South Korea

ADSCs (human)

DMEM

serum-free

2D

24 h

-

Filter concentration of filtered supernatant

-

In vitro, in vivo

[32]

2022

China

ADSCs (mouse)

MSC Medium

serum-free

2D

24 h

Curcumin (10 µM)

Differential ultracentrifugation

-

In vitro, in vivo

[43]

2024

China

ADSCs (rat)

DMEM/F12

10% EV-free FBS

2D

48 h

-

Differential ultracentrifugation

-

In vitro, in vivo

[34]

2021

China

ADSCs (rat)

α-MEM

10% EV-free FBS

2D

48 h

-

Density gradient ultracentrifugation

-

In vitro

[52]

2023

The Netherlands

BMSCs (human)

α-MEM

5% EV-free hPL

2D

48 h

-

Differential ultracentrifugation

38.8 EVs/cell

In vivo

[30]

2022

China

BMSCs (human)

DMEM

serum-free

2D

-

-

Differential ultracentrifugation

-

In vitro

[44]

2022

China

BMSCs (human)

α-MEM

serum-free

2D

48 h

-

Exosome Purification Kit

-

In vitro, in vivo

[27]

2022

China

BMSCs (human)

DMEM/F12

10% EV-free FBS

2D

48 h

Hypoxia

Differential ultracentrifugation

-

In vitro, in vivo

[22]

2021

Germany

BMSCs (human)

α-MEM

10% EV-free FBS

2D

48 h

-

Differential ultracentrifugation

3–4 × 1010 EVs/ml

In vitro

[66]

2021

China

BMSCs (human)

DMEM

10% EV-free FBS

2D

48 h

-

Exosome Purification Kit

-

In vitro

[38]

2021

China

BMSCs (human)

CMD (UR51101)

(serum-free)

2D

48 h

-

Exosome Purification Kit

-

In vitro, in vivo

[23]

2021

United Kingdom

BMSCs (human)

DMEM

5% EV-free hPL

2D

48 h

-

Differential ultracentrifugation

1.38 × 1011 EVs/ml 635 × EVs/cell (OA)

1.12 × 1011 EVs/ml

709 EVs/cell (healthy)

In vitro

[33]

2021

China

BMSCs (human)

DMEM

serum-free

2D

48 h

-

Filter concentration of filtered supernatant

1.05 × 107 EVs/ml

In vitro

[21]

2020

Germany

BMSCs (human)

α-MEM

10% EV-free FBS

2D

48 h

-

Differential ultracentrifugation

-

In vitro

[12]

2020

Italy

BMSCs (human)

α-MEM

serum-free

2D

72 h

FBS/XFS

Differential ultracentrifugation

0.5 µg/106 cells

15 EVs/cell (FBS)

1.5 µg/106 cell

30 EVs/cell (XFS)

In vitro

[54]

2024

China

BMSCs (mouse)

DMEM/F12

10% EV-free FBS

2D

-

EMF/USPIO

Differential ultracentrifugation

-

In vivo

[40]

2022

China

BMSCs (mouse)

DMEM

serum-free

2D

48 h

-

Differential ultracentrifugation

-

In vitro

[47]

2023

Iran

BMSCs (rabbit)

DMEM

10% EV-free FBS

2D/3D

-

Chondrogenesis

Chondrocyte co-culture

Differential ultracentrifugation

21.23 µg/106 cells (2D)

0.83 µg/106 cells (3D)

In vivo

[59]

2022

Iran

BMSCs (rabbit)

DMEM

10% EV-free FBS

3D

7 days

Shaking

Size-exclusion chromatography

10 µg/106 cells

In vivo

[29]

2024

China

BMSCs (rat)

DMEM/F12

10% EV-free FBS

3D

-

SA/HA

Hydrogels

Ultracentrifugation of filtered supernatant

300 EVs/cell (2D)

1.5 × 103 EVs/cell (3D)

In vivo

[26]

2021

China

BMSCs (rat)

DMEM/F12

10% EV-free FBS

2D

48 h

Hypoxia

Filter concentration of filtered supernatant

-

In vitro, in vivo

[67]

2021

Italy

BMSCs vs. ADSCs (human)

DMEM/α-MEM

serum-free

2D

24 h

-

Differential ultracentrifugation

-

In vitro

[39]

2022

Italy

BMSCs vs. SFMSCs (horse)

DMEM

10% EV-free FBS

2D

24 h

-

Ultracentrifugation of filtered supernatant

1.9 × 1010 EVs/ml

(BMSCs)

1.7 × 1011 EVs/ml

(SFMSCs)

In vitro

[36]

2023

China

DFCs (rat)

MSC Medium

serum-free

2D

48 h

-

Exosome Purification Kit and filter concentration

-

In vitro

[50]

2023

USA

SFMSCs (rat)

DMEM

serum-free

2D

48 h

-

Differential ultracentrifugation

7.5 × 107 EVs/ml

In vivo

[25]

2021

China

SMSCs (human)

DMEM

serum-free

2D

48 h

LPS (100 ng/ml)

Differential ultracentrifugation

-

In vitro, in vivo

[41]

2021

China

SMSCs (human)

DMEM

10% EV-free FBS

2D

48 h

-

Differential ultracentrifugation

-

In vitro, in vivo

[53]

2021

China

SMSCs (human)

CDM (StemGro)

(serum-free)

2D

48 h

-

Density gradient ultracentrifugation

-

In vivo

[16]

2023

Spain

UCMSCs (human)

DMEM

serum-free

2D

48 h

-

Size-exclusion chromatography

2.7 × 1010 EVs/ml

35 µg/ml

In vitro

[35]

2023

China

UCMSCs (human)

α-MEM

10% EV-free FBS

2D

48 h

-

Differential ultracentrifugation

2.2 × 1010 EVs/ml

In vitro, in vivo

[55]

2023

China

UCMSCs (human)

StemXVivo

10% EV-free FBS

2D

48 h

-

Differential ultracentrifugation

0.5 µg/ml

In vivo

[56]

2022

China

UCMSCs (human)

MSCYF01-500/

MSCYF02-20

2D

-

-

Size-exclusion chromatography

-

In vivo

[57]

2022

China

UCMSCs (human)

DMEM

serum-free

2D

48 h

-

Differential ultracentrifugation

-

In vivo

[28]

2022

Vietnam

UCMSCs (human)

DMEM/F12

10% EV-free FBS

2D

48 h

TGF-β (10 ng/ml)

TNF-α (20 ng/ml)

INF-α (20 ng/ml)

Differential ultracentrifugation

-

In vitro

[58]

2022

China

UCMSCs (human)

DMEM

10% EV-free FBS

2D

48 h

-

Differential ultracentrifugation

-

In vivo

[48]

2021

China

UCMSCs (human)

α-MEM

10% EV-free FBS

2D

48 h

-

Differential ultracentrifugation

-

In vivo

[42]

2021

China

UCMSCs (human)

MSCYF01-500/

MSCYF02-20

2D

48 h

-

Size-exclusion chromatography

2.3 × 107 EVs/ml

(20.920 µg/ml)

61.1 EVs/cell

(62.8 µg/106 cells)

In vitro, in vivo

[37]

2020

China

UCMSCs (human)

12–725 F

10% EV-free FBS

2D

72 h

-

Differential ultracentrifugation

8.2 × 106 EVs/ml

In vitro, in vivo

  1. FBS: foetal bovine serum; CMD: chemically-defined medium; hPL: human platelet lysate; XFS: xeno-free supplement; EMF: electromagnetic field; USPIO: ultrasmall superparamagnetic iron oxide; SA/HA: sodium alginate/hyaluronic acid