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Table 2 Preclinical studies of stem cell therapy for ICH

From: Application of stem cells and exosomes in the treatment of intracerebral hemorrhage: an update

References

Drug delivery route

Number of cells/exosomes

Type of ICH

model Rat

Sample Size

Treatment Day after ICH

Earliest effective time (post ICH)

Behavioral recovery

Nonaka et al. [61]

Intraventricular

1 × 105

ESCs

Rat

Col VII

Sham 5

Treatment 10

7 d

NA

NA

Chen et al. [62]

Intraventricular

2–4 × 105 AD-MSCs

Rat

Col IV

Control 40 Treatment 40

2 d

3 d

Zea Longa 5-grade scale↑

Cui et al. [63]

Intravenous

5 × 106

MSCs

Rat

ABI

Control 15

Treatment 15

1 h

and

24 h

3 d

NSS↓

Wang et al. [38]

Intravenous

1 × 106 MSCs

Rat

ABI

Sham 12

Control 24 Treatment 24

NA

14 d

mNSS↓

MLPT scores↓

Chen et al. [39]

Intravenous

5 × 106 MSCs

Rat

Col IV

NA

2 h

3 d

mNSS↓

Wang et al. [42]

Intravenous

1 × 106 MSCs

Rat

Col VII

Control 6 treatment6

1 h

7 d

mNSS↓

References

Drug delivery route

Number of cells/exosomes

Type of ICH

model Rat

Sample Size

Treatment Day after ICH

Earliest effective time (post ICH)

Behavioral recovery

Seyfried et al. [52]

Intravenous

0.5–1 × 106 MSCs

Rat

ABI

Control 9 Treatment 18

24 h

7 d

mNSS↓

corner-turn test↑

Nan et al. [57]

Intravenous

2.4–3.2

 × 106

MSCs

Rat

Col VII

NA

24 h

7 d

limb-placement tests↑

stepping tests↑

body-swing tests↑

Yang et al. [64]

Intravenous

1 × 106

AD-MSCs

Rat

Col VII

Control 6 Treatment 9

24 h

7 d

mNSS↓

Kim et al. [65]

Intravenous

3 × 106

AD-MSCs

Rat

Col VII

Control 16 Treatment 16

24 h

28 d

MLPT scores↓

Jeong et al. [66]

Intravenous

5 × 106 NSCs

Rat

Col V

Control 13 Treatment 12

24 h

14 d

rotarod test ↑

MLPT scores ↓

Vaquero et al. [67]

Intracerebral

5 × 106 MSCs

Rat

Col V

Control 20 Treatment 20

2 m

4 m

rotarod tests↑

VTB tests↑

Bao et al. [68]

Intracerebral

2 × 105 MSCs

Rat

Col VII

Control 67 Treatment 65

24 h

3 d

mNSS↓

References

Drug delivery route

Number of cells/exosomes

Type of ICH

model Rat

Sample Size

Treatment day after ICH

Earliest effective time (post ICH)

Behavioral recovery

Liang et al. [69]

Intracerebral

1 × 106 MSCs

Rat

Col IV

Sham 8

Control 16 Treatment 16

24 h

7 d

MLPT scores ↓ vibrissae-elicited forelimb-placing test↑

Otero et al. [70]

Intracerebral

2 × 106 MSCs

Rat

Col IV

Control 48 Treatment 48

2 h

NA

NA

Yang et al. [71]

Intracerebral

5 × 105 MSCs

Rat

Col I

Control 10 Treatment20

3 d

7 d

mNSS↓

Otero et al. [72]

Intracerebral

2 × 106 MSCs

Rat

Col IV

Control 10 Treatment10

3 d

3 w

mNSS↓

Rotarod test↑

Otero et al. [73]

Intracerebral

5 × 106 MSCs

Rat

Col IV

Control 10 Treatment 10

2 m

3 m

mNSS↓

Rotarod tests↑

VTB tests↑

locomotor activity↑

Feng et al. [74]

Intracerebral

1–5 × 106 MSCs

Monkey

ABI

Control 8 Treatment16

1 w

or

4 w

2 w

or

5 w

Neurologic deficit scores↓

References

Drug delivery route

Number of cells/exosomes

Type of ICH

Model Rat

Sample Size

Treatment day after ICH

Earliest effective time (post ICH)

Behavioral recovery

Nagai et al. [75]

Intracerebral

2 × 105 MSCs

Rat

Col VII

Control 4 Treatment 14

7 d

8 d

Rotarod test↑

Seyfried et al. [76]

Intracerebral

3, 5 and 8 × 106 MSCs

Rat

ABI

Control 27 Treatment 27

24 h

7 d

mNSS↓

corner-turn test↑

Zhang et al. [77]

Intracerebral

1 × 105 MSCs

Rat

Col IV

Control 60 Treatment 60

6 h

24 h

mNSS↓

Gao et al. [78]

Intracerebral

5 × 105 NSCs

Rat

Col IV

Sham 20

Control 48 Treatment 26

3 h

3 d

mNSS↓

Wakai et al. [79]

Intracerebral

1 × 105 NSCs

Mouse

ABI

NA

3 d

21 d

Cylinder tests↑

corner-turn tests↑

Wang et al. [80]

Intracerebral

1 × 106 NSCs

Rat

Col VII

Control 26 Treatment 13

3 d

24 d

MLPT scores↓

Lee et al. [81]

Intracerebral

2 × 105 NSCs

Mouse

Col IV

Control 28 Treatment 61

7 d

8 d

Rotarod test↑

MLPT scores↓

References

Drug delivery route

Number of cells/exosomes

Type of ICH

Model Rat

Sample Size

Treatment day after ICH

Earliest effective time (post ICH)

Behavioral recovery

Lee et al. [82]

Intracerebral

2 × 105 NSCs

Mouse

Col IV

Control 20 Treatment 18

7 d

5 w

Rotarod test↑

MLPT scores↓

Lee et al. [83]

Intracerebral

2 × 105 NSCs

Mouse

Col IV

Control 18 Treatment 39

7 d

8 d

Rotarod test↑

MLPT scores↓

Lee et al. [84]

Intracerebral

2 × 105 NSCs

Mouse

Col VII

Control 30 Treatment 31

7 d

21 d

Rotarod test↑

MLPT scores↓

Lee et al. [85]

Intracerebral

2 × 105 NSCs

Mouse

Col IV

Control 20 Treatment 50

7 d

8 d

Rotarod test↑

MLPT scores↓

Qin et al. [46]

Intracerebral

1 × 106 iPSCs

Rat

Col VII

Sham 30

Control 63 Treatment 59

6 h

14 d

MLPT scores↓

Qin et al. [44]

Intracerebral

2 × 106 iPSCs

Rat

Col VII

NA

24 h

14 d

mNSS↓

MLPT scores↓

Qin et al. [45]

Intracerebral

1 × 106 iPSCs

Rat

Col VII

Sham 12

Control 24 Treatment 12

24 h

14 d

mNSS↓

MLPT scores↓

References

Drug delivery route

Number of cells/exosomes

Type of ICH

model Rat

Sample size

Treatment day after ICH

Earliest effective time (post ICH)

Behavioral recovery

Seyfried et al. [86]

Intra-arterial

1 × 106 MSCs

Rat

ABI

Control 18 Treatment 18

24 h

7 d

mNSS↓

corner-turn test↑

Li et al. [87]

Intra-arterial

4 × 106 NSCs

Rat

Col VII

Control 8 Treatment 40

2, 7, 14, 21 or 28 d

28 d

Rotarod tests↑

beam-walking tests↑

limb-placing tests↑ spontaneous cycling tests↑

Zhang et al. [88]

Intra-arterial intravenous intraventricular

2 × 106 MSCs

Rat

Col VII

Blank 5

Sham 20

Control 20 Treatment 60

1, 3, 5

and 7 d

24 h

Beam-walking test ↑

(intravenous group →)

Xie et al. [89]

Intracerebral, intravenous

2 × 105(IC)

2 × 106(IV) MSCs

Rat

Col VII

Sham 10

Control 16 Treatment 36

NA

7 d

mNSS↓

Lee et al. [90]

Intravenous intracerebral

5 × 106 (IV) 1 × 106 (IC) NSCs

Rat

Col VII

Sham 30

Control 30 Treatment 120

2 h

or

24 h

24 h

MLPT scores↓

Reference

Drug delivery route

Number of cells/exosomes

Type of ICH

Model Rat

Sample Size

Treatment day after ICH

Earliest effective time (post ICH)

Behavioral recovery

Sun et al. [60]

Intranasal

1 × 106 MSCs

Mouse

Col IV

NA

3 d

and

7 d

14 d

mNSS↓

adhesive removal↑

rotarod tests↑

open field tests↑

  1. ABI, autologous blood injection; AD-MSCs, adipose-derived mesenchymal stem cells; Col, collagenase; ESCs, embryonic stem cells; ICH, intracerebral hemorrhage; iPSCs, induced pluripotent stem cells; MLPT, modified limb-placing test; mNSS, modified NSS; MSCs, mesenchymal stem cells; NA, not available; NSCs, neural stem cells; NSS, neurological severity score; VTB, video-tracking box tests; h, hours; d, days; w, weeks; m, months;↑, increased or improved; ↓, decreased; and → , no statistical significance