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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