Table 4 Primary outcomes of the included studies.

From: Mesenchymal stem cell therapy in perinatal arterial ischemic stroke: systematic review of preclinical studies

Reference

Functional outcome

Participation

Survival of the animals

 

Motor performance

Cognitive performance

Sensory function

Social interaction

 
 

Test

↑↓↔

Test

↑↓↔

Test

↑↓↔

Test

↑↓↔

 

Cho et al. (2016);34 Korea

Rotarod test

2 weeks post MSC: ↔; 8 weeks post MSC: ↑ only MSC-EE group

NR

 

NR

 

NR

 

NR

Grip strength test

2 weeks post MSC: ↔; 8 weeks post: ↑ only MSC-EE group

Ding et al. (2015)22

NR

 

Morris water maze

21 days post injury:

NR

 

NR

 

NR

Ding et al. (2017)23

Hanging wire

16, 22, and 28 days post injury: ↑

NR

 

NR

 

NR

 

NR

Vertical pole test

16, 22, and 28 days post injury: ↑

Kim et al. (2012);35 Korea

Rotarod test

26 and 27 days post injury: ↔; 28 days post injury: ↑

NR

 

NR

 

NR

 

Survival at 28 days post injury; Sham control group =100%; MCAO-MC (vehicle) group = 40%; MCAO-MM (MSCs) group = 83%

Cylinder test

28 days post injury: ↔

Larpthaveesarp et al. (2021)37

Cylinder test

P61, P62 postnatal:; MACO+7 d MSC; ↔ MACO+3 d MSC

Novel object recognition

P54: ↔ ↑only for MSC/EPO and EPO

    

MCAO+Vehicle group = 89%; 3 d MCAO+MSCs = 100%; 7 d MCAO+MSCs = 80%

Open field test

P59:

Lee et al. (2010);36 Korea

Rotarod test

14, 20, 30, and 40 days post MSCs: ↔

NR

 

NR

 

NR

 

NR

Cylinder test

Overall: ↑; 14 days post MSCs: ↔; 20 days post MSCs: ↑

Li et al. (2014);24 China

  

Shuttle box test

1–5 days post MSCs:

NR

 

NR

 

NR

Ohshima et al. (2015);40 Japan

NR

 

NR

 

NR

 

NR

 

NR

Sakai et al. (2018);41 Japan

Beam walk test

25 days post MSCs: ↑

NR

 

NR

 

NR

 

NR

van Velthoven et al. (2017);38 USA

Cylinder rearing test

28 days post injury: ↑

NR

 

NR

 

NR

 

The survival rate at the end of the study is unclear; before the randomization of the treatment groups and 3 days after tMCAO the survival rate is reported to be 87%

van Velthoven et al. (2013);33 Netherlands

Cylinder rearing test

14, 21, and 28 days post injury: ↑ at all timepoints

NR

 

NR

 

NR

 

Unclear by the end of the study; 87% post-MCAO and prior to randomization to the treatment groups

Adhesion removal test

28 days post injury: ↑

van Velthoven et al. (2010);29 Netherlands

Cylinder rearing test

10, 21, and 18 days post injury: ↑ MSC-3: versus VEH; 21 and 28 days post injury: ↑ MSCS-3+10: versus VEH, versus MSC-3

NR

 

NR

 

NR

 

Approx. 90% post HI insult

Rotarod treadmill

21 days post injury: ↑MSC-3, MSC-3+10 versus VEH 28 days: ↑MSC-3, MSC-3+10 versus VEH↑ MSC-3+10 versus MSC-3

van Velthoven et al. (2010);31 Netherlands

Cylinder rearing test

21 and 28 days post injury: ↑ versus VEH

NR

 

NR

 

NR

 

Approx. 90% post HI insult

van Velthoven et al. (2010);32 Netherlands

Cylinder rearing test

10 and 21 days post injury: ↑ versus VEH

NR

 

NR

 

NR

 

Approx. 90% post HI insult

van Velthoven et al. (2012);30 Netherlands

Cylinder rearing test

21 and 28 days post injury: ↑ versus VEH

NR

 

NR

 

NR

 

NR

Wei et al. (2015);39 USA

Adhesion removal test

10, 17, and 24 days post injury: ↑ versus saline

NR

 

Modified buried food-finding test

17 and 24 days after injury: ↑

Social interaction test

17 and 24 days after injury: ↑ versus Saline

NR

Home-cage activity

17 and 24 days after injury: ↑ versus saline

Xia et al. (2010);25 China

Modified neurological severity score: muscle status, abnormal movement Beam balance test reflex absence

14, 21, and 20 days post MSCs: ↑ overall score

NR

 

Modified neurological severity score: sensory tests

14, 21, and 20 days after MSCs: ↑overall score

NR

 

NR

Yang et al. (2020)28

NR

 

Spatial version of the Morris water maze task

4 weeks post injury: ↑

NR

 

NR

 

NR

Zhang et al. (2014);26 China

Longa scoring

6 h and 7 and 20 days post injury: ↑

Morris water maze task

4 weeks post injury: ↑ MSC-24 h versus MSC-72 h and VEH-24 h

NR

 

NR

 

NR

Rotarod testing

20 days post injury: ↑

Zhou et al. (2015)27

NR

 

Morris water maze test; object-in-place task

4 weeks post MSC:↑; 6 weeks old animals: ↑

NR

 

NR

 

NR

  1. NR not reported, ↑ significant increase in performance, ↓ significant decrease in performance, ↔ no significant change in performance compared to control group, MSC mesenchymal stem cell administration, MCAO middle cerebral artery occlusion.