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Table 2 Autophagy may regulate MSC activities in vivo and repair I/R-induced injury in different tissues

From: Modulating autophagy in mesenchymal stem cells effectively protects against hypoxia- or ischemia-induced injury

Tissue

MSC source

Dose

Route

Animal

Treatment

Time point

Autophagy

Effect

Reference

Heart

Bone marrow

1 × 106

Injection into the peri-infarcted areas

Mouse

1% O2

Transplantation immediately after MI

↑

Alleviate the apoptotic rate of cardiomyocytes; preserve heart function; eliminate fibrosis

[21]

Bone marrow

Exosomes derived from 5 × 106 cells

Injection into the anterior and lateral part of the visibly injured region

Rat

N/A

Transplantation prior to reperfusion

↑

Decrease the apoptosis rate of MSCs; reduce the myocardial infarct size

[91]

N/A

2 × 105

Injection into the peri-infarcted areas

Mouse

N/A

Transplantation at 30 min after MI

↓

Reduce infarct size; improve cardiac function

[92]

N/A

5 μg MSC-derived exosomes

Injection into the peri-infarcted areas

Mouse

N/A

Transplantation at 30 min after MI

↓

Reduce infarct size; improve cardiac function

[92]

Bone marrow

1 × 106

Intramyocardial injection

Rat

Overexpression of Let-7b in MSCs

Transplantation immediately after MI

↓

Improve left ventricular function and microvessel density

[93]

Brain

Bone marrow

5 × 106

Retro-orbital injection

Rat

N/A

Transplantation after 1 h and 24 h reperfusion

↓

Promote neurite growth and regeneration

[104]

Bone marrow

2 × 106

Intravenous injection

Rat

N/A

Transplantation at 30 min after TBI

↓

Promote histological and functional recovery in the brain

[105]

Adipose

100 μg/kg/day of MSC-derived exosomes

Injection into the lateral cerebral ventricle

Rat

Overexpression of PEDF

Transplantation at 3 days prior to MCAO surgery

↑

Inhibit neuronal apoptosis; ameliorate cerebral I/R injury

[108]

Bone marrow

1 × 106

Injection into the striatum of the ipsilateral hemisphere

Rat

Overexpression of HIF-1α

Transplantation at 4 h after MCAO

↑

Reduce brain infarct volume; improve neurobehavioral outcome

[103]

Bone marrow

5 × 106

Injection into the superficial dorsal veins

Rat

Overexpression of HO-1

Immediate transplantation following the surgery

↑

Exert protective effects on liver grafts following reduced-size liver transplantation

[116]

 

Bone marrow

1 × 106

Portal vein

Rat

Overexpression of heat shock protein (HSP)

Transplantation at 60 min after reperfusion

↑

Decrease the levels of serum aminotransferases and Suzuki scores; improve cell survival and histopathology

[117]

Retina

Bone marrow

5 × 104

Intravitreal transplantation

Rat

N/A

Transplantation at 24 h postischemia

↑

Eliminate ischemic damage in the retina

[120]

 

Bone marrow

4 × 106

Injection into the ischemic muscle along the femoral artery

Rat

5% O2

Transplantation immediately after surgery

↑

Upregulate the pro-angiogenic effects and therapeutic effects of engrafted MSCs in the lower limb of ischemic diabetic rats

[76]

 

Adipose

1.0 × 107

Injection into the left adductor muscle

Mouse

Apelin

Transplantation immediately after surgery and lasting for consecutive 14 days

↑

Enhance the survival of MSCs in ischemic hindlimbs; restore hindlimb blood perfusion; repair limb functions in peripheral arterial disease

[122]