Table 1 Summary of the animal studies eligible for this review

C57BL6 mice

(male)

Focal ischemia

(MCAO)

Brain

Allograft:

Placenta

IV, 100 μg, Immediately after

Reperfusion

Yes

Yes

Decreased infarct size 72 h post-ischemia

[25]

Wistar rat

Focal ischemia (MCAO)

Brain

Xenograft:

hUC-MSCs

Direct ICVs, 10 μL of healthy mitochondria isolated from 3 × 10⁷ MSCs, After reperfusion (within 10 min)

Not reported

Not reported

Reduced Infarct size 72 h after ischemia;

Improved motor function after 24 h

[31]

SD rat

(male)

Focal ischemia (MCAO)

Brain

Autograft:

Pectoralis major muscle

Direct ICVs, 5 × 10⁶, Immediately after reperfusion

Yes

Yes

Improved motor functions after MCAO, with reduced infarct volume and apoptosis

[32]

SD rats

(male)

Focal ischemia

(MCAO)

Brain

Xenograft:

BHK-21 cells

Direct IC, 75 μg or IA (femoral), 750 μg,

24 h post-MCAO

Not reported

Not reported

IC and IA reduced infarct size 4 weeks post-ischemia and improved functional rotarod and grip strength performance for up to 1-month post-transplantation

[33]

1) bEnd3 and PC12 cell

2) C57BL6 mice

(male)

1) OGD,

2) TBI

1) Cell,

2) Brain

Allograft:

BDMts

1) Co-culture

2) IC into the ipsilateral cortex, 1.1 × 10⁷ mitochondria/μL × 10 μL,

10 min post-TBI

Yes

Yes

1) In vitro: improved cellular respiration and synaptic plasticity

2) In vivo: Reduced apoptosis, BBB damage, and brain edema

[30]

Yorkshire pigs

(female)

Focal ischemia

Heart

Autograft:

Pectoralis major muscle

IA (coronary), 1 × 10⁹,

120 min after reperfusion

Yes

Not reported

Reduced myocardial infarct size and enhanced regional and global myocardial function post-reperfusion

[34]

Yorkshire Pigs

(female)

Focal ischemia

Heart

Autograft:

Pectoralis major muscle

Subendocardial injection 8 times, 1.3 × 10⁷ mitochondria per injection site, 1 min before reperfusion

Yes

Not reported

No change in inflammatory and cytokine activation markers; decreased infarct size but no change in global function

[36]

Yorkshire swine (female)

Focal ischemia

Heart

Autograft:

Pectoralis major muscle

IA (coronary), 1 × 10⁹,

Immediately on reperfusion

Not reported

No

Improved myocardial function, perfusion, and infarct size

[37]

Yorkshire Pigs

(female)

Focal ischemia

Heart

Autograft:

Pectoralis major muscle

Single IA (coronary): 1 × 10⁹, 15 min before regional ischemia

Serial IA (coronary): 1 × 10⁹ mitochondria × 10 injections, Every 5 min since 60 min before ischemia

Yes

Yes

Reduced myocardial infarct size, improved myocardial function;

no difference between single and serial injections

[38]

New Zealand White rabbits (female)

1) Image study:

Global or regional ischemia

2) Function study;

regional ischemia

Heart

1) Xenograft:

Human cardiac fibroblasts

2)　Autograft:

Liver

2) IA (coronary), 1 × 10⁸,

Upon reperfusion

Not reported

Yes

1) Mitochondria were observed in interstitial spaces, associated with blood vessels, and cardiomyocytes

2) Reduced infarct size and enhanced myocardial function

[39]

New Zealand white rabbits (male)

Focal ischemia

Heart

Autograft:

Pectoralis major muscle

Direct injection 8 times, 1.2 × 10⁶ per injection site, 1 min before reperfusion

Not reported

Yes

Reduced myocardial infarct size and enhanced regional myocardial function post-reperfusion

[40]

C57BL/6 J mice (male)

Focal ischemia

Heart

Allograft:

Gastrocnemius muscle

IA (coronary), 1 × 10⁸,10 min before organ harvest and 5 min after transplantation

Not reported

Yes

Enhanced graft function and decreased graft tissue injury

[41]

C57BL/6 mice (male)

Focal ischemia

Heart

Not reported

Direct injection at myocardium of the left ventricle, 5 × 10⁴,

During 24 h perfusion at 4 different points

Not reported

Not reported

Mitochondrial transplantation inhibited cardiomyocyte apoptosis in vitro

In vivo transplantation of Alda-1-treated mitochondria limited infarction size after I/R injury

[42]

Yorkshire pigs (female)

Global ischemia

Heart

1) 1^st, Autograft: Pectoralis major muscle

2) 2^nd, Allograft: swine cardiac fibroblast cell

IA (coronary), 5 × 10⁹,

1) 15 min post-reperfusion

2) 2 h post-reperfusion

Yes

Yes

Preserved myocardial function and oxygen consumption and, decreased infarct size

[35]

Wistar rats (male)

Focal ischemia

Kidney

Autograft:

Pectoralis major muscle

IA (renal), 7.5 × 10⁶, 5 min before reperfusion

Not reported

Not reported

Increased renal function, renal cell repair, and proliferation capacity

[43]

Yorkshire pigs (female)

Focal ischemia

Kidney

Autograft: Sternocleidomastoid muscle

Single IA (renal artery), 1 × 10⁹,

Immediately at reperfusion

Yes

Yes

No safety issues detected

Increased GFR and urine output, decreased serum creatinine and BUN

[44]

C57BL/6 J mice (male)

Focal ischemia

Hindlimb

Allograft:

Muscle

Direct injection, 1 × 10⁶–1 × 10⁹ per gram muscle wet weight, 15 min after reperfusion

Not reported

Yes

Decreased infarct size and apoptosis; improved hindlimb function

[45]

C57BL/6 J mice (male)

Focal ischemia

Lung

Allograft: Gastrocnemius muscle

IA (pulmonary), 1 × 10⁸, or Aerosol delivery to whole lung by nebulization, 3 × 10⁸,

Immediately at reperfusion

Yes

Yes

Both delivery methods improved lung mechanics and decreased

lung tissue injury

[46]

SD rats

(male)

Focal ischemia

Spinal cord

Allograft:

Soleus muscle

IV (jugular), 100 μg,

5 min before reperfusion

Yes

Yes

Attenuated inflammatory, ER stress, and neuro-apoptotic reactions

Improvement in motor function

[47]

SD rats

(male)

Focal ischemia

Liver

Allograft:

Liver

Portal vein, 10 mg,

Upon reperfusion

Yes

Not reported

³¹P-MRS showed that the hepatic levels of ATP and NADH were higher in the m-Mito group than in the IRI group. The m-Mito group decreased the liver injury score and inflammatory cell infiltration in liver compared to the IRI group

[48]