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Table 3 Mesenchymal stem cell therapy in animal models of hind limb ischemia

From: Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia

Reference

Source of MSCs

Recipient

Intervention

Site of injection

Outcome

[64]

Mouse AT-MSCs ± GF-rich medium

Mouse

IM injection of 1 × 106 MSCs

10 days after HLI

Three sites: proximal and distal arterial stumps

↑ limb perfusion

[32]

Mouse BM-MSCs

Mouse

IM injection of 0.5 × 106 MSCs

2 days after HLI

Multiple sites at TA and ischemic thigh

↑ limb perfusion, ↑ capillary density, ↑ muscle regeneration

[45]

Mouse BM-MSCs ± EGF

Mouse

IM injection of 0.6 × 106 MSCs

0 hour after HLI

Three sites: quadriceps, gluteus, and TA

↑ limb perfusion, ↑ capillary density

[21]

Mouse BM-MSCs

Mouse

IM injection of 1 × 106 MSCs

24 hours after HLI

Six sites of adductor muscles adjacent to and within 1 mm proximal or distal to ligation sites

↓ limb loss, ↑ vascular density, ↓ muscle atrophy and fibrosis

[65]

Mouse BM-MSCs ± zinc

Mouse

IM injection of 5 × 106 MSCs

0 hour after HLI

Five sites of ischemic thigh

↑ limb perfusion, ↑ capillary density

[66]

Mouse BM-MSCs ± simvastatin

Mouse

IM injection of 2 × 106 MSCs

0 hour after HLI

Five sites of ischemic thigh

↑ limb perfusion, ↑ capillary density

[67]

Mouse BM-MSCs ± simvastatin

Mouse

IM injection of 5 × 106 MSCs

0 hour after HLI

Five sites of ischemic thigh

↑ limb perfusion, ↑ capillary density

[68]

Mouse BM-MSCs ± PGIS

Mouse

IM injection of 1 × 106 MSCs

0 hour after HLI

Six to eight ischemic sites

↑ limb perfusion, ↑ capillary density, ↓ limb loss and necrosis

[69]

Mouse endometrium-derived MSCs

Mouse

IM injection of 1 × 106 MSCs

on days 0, 2, and 4

Hind-limb muscle below area of ligation

↓ limb necrosis

[70]

Rat BM-MSCs

Rat

IM injection of 5 × 106 MSCs

3 weeks after HLI

Anteromedial muscle compartment left thigh

↑ limb perfusion, ↑ vascular density, ↑ arteriolar density

[12]

Rat BM-MSCs

Rat

IM injection of 5 × 106 MSCs

0 hour after HLI

Ischemic thigh muscles

↓ limb loss and necrosis, ↑ limb perfusion, ↑ capillary density, ↑ endothelial and vascular smooth muscle differentiation

[11]

Rat FM-MSCs and rat BM MSCs

Rat

IM injection of 5 × 106 MSCs

24 hours after HLI

Ischemic thigh

↑ limb perfusion, ↑ capillary density

[71]

Rat BM-MSCs ± angiopoietin-1

Rat

IM injection of 5 × 106 MSCs

0 hour after HLI

Two sites of ischemic limb

↑ limb perfusion, ↑ capillary density

[72]

Rat BM-MSCs ± netrin-1

Rat

IM injection of 1 × 106 MSCs

? hours after HLI

Ischemic limb

↓ limb loss and necrosis, ↑ angiographic score, ↑ capillary density

[73]

Human AT-MSCs

Rat

IM injection of 1 × 107 MSCs

0 hour after HLI

Ischemic limb

↑ limb perfusion, ↑ capillary density

[20]

Human AT-MSCs

Mouse

TV injection of 5 × 105 MSCs

24 hours after HLI

Not applicable

↓ limb necrosis, ↑ limb perfusion

[74]

Human AT-MSCs

Mouse

IM injection of 5 × 105 MSCs

1 or 7 days after HLI

Three different sites of ischemic leg

↓ limb loss, ↑ limb perfusion, ↑ capillary density (7 days > 1 day after HLI)

[75]

Human AT-MSCs ± spheroid culture

Mouse

IM injection of 1 × 107 MSCs

24 hours after HLI

Gracilis muscle

↑ limb perfusion, ↑ capillary density, ↓ limb loss and necrosis

[34]

Human AT-MSCs

Mouse

IM injection of 1 × 106 MSCs

0 hour after HLI

Three separate regions from ankle up to thigh regions

↓ amputation and limb necrosis, ↑ limb perfusion, ↑ myogenic differentiation, ↑ capillary density

[76]

Human AT-MSCs loaded in fibrin gel ± FGF2

Mouse

IM injection of 5 × 106 MSCs

24 hours after HLI

Gracilis muscle

↑ MSC survival in ischemic muscles, ↓ muscle degeneration and fibrosis, ↑ limb perfusion, ↓ limb loss and necrosis

[77]

Human AT-MSCs ± GCP2

Mouse

IM injection of 1 × 106 MSCs

24 hours after HLI

Three sites of ischemic leg

↑ limb perfusion

[17]

Human AT-MSCs and human BM-MSCs

Mouse

IM injection of 1 × 106 MSCs

24 hours after HLI

Gastrocnemius, gracilis, and quadriceps

↑ limb perfusion, ↓ muscle injury

[62]

Human BM-MSCs

Mouse

LV injection of 5 × 105 MSCs

24 hours after HLI

LV

↑ limb perfusion

[63]

Human BM-MSCs

Mouse

IM injection of 1 × 106 MSCs

24 hours after HLI

Three different sites of the injured area

↑ limb perfusion

[78]

Human ESC-MSCs

Rat

IM injection of 0.5 × 106 MSCs

24 hours after HLI

Five sites at femoral biceps, semitendinous, semimembranous, and adductor muscle

↑ capillary density

[79]

Human FAM-MSCs

Mouse

IM injection of 1 × 106 MSCs

24 hours after HLI

Three sites of ischemic leg

↑ limb perfusion, ↑ capillary density

[16]

Human iPSC-MSCs and human BM-MSCs

Mouse

IM injection of 3 × 106 MSCs

0 hours after HLI

Four sites of gracilis muscle in medial thigh

↓ limb loss and necrosis, ↑ limb perfusion, improved ambulatory and tissue damage scores, ↑ myogenesis, smooth muscle, and endothelial differentiation, ↓ fibrosis and inflammation

[51]

Human placenta-derived MSCs

Mouse

IM injection of 1 × 106 MSCs

5 hours after HLI

Two sites on right thigh

↑ limb perfusion, functionality, and capillary density, ↓ oxidative stress and inflammation

[80]

Human placenta-derived MSCs

Mouse

IM injection of 1 × 106 MSCs

1 week after HLI

Five or six sites of the ischemic sites

↑ limb perfusion

[81]

Human UCB-MSCs loaded in fibrin gel ± FGF2

Mouse

IM injection of 2 × 106 MSCs

24 hours after HLI

Gracilis muscle

↑ MSC survival in ischemic muscles, ↓ muscle degeneration and fibrosis

[82]

Human UCB-MSCs

Mouse

IM injection of 1.3 × 106 MSCs

0 hour after HLI

Not specified

↓ limb loss and necrosis, ↑ limb perfusion

[83]

Human UCB-MSCs

Mouse

IM injection of 1 × 105 MSCs

0 hour after HLI

Eight to ten injections at gastrocnemius, semimembranosus, rectus muscles

No difference in capillary density, ↑ muscle regeneration

  1. ↑, increase of; ↓, decrease of; AT-MSC, adipose tissue-derived mesenchymal stem cell; BM-MSC, bone marrow-derived mesenchymal stem cell; ESC-MSC, embryonic stem cell-derived mesenchymal stem cell; EGF, epidermal growth factor; FAM-MSC, fetal amniotic membrane-derived mesenchymal stem cell; FGF2, fibroblast growth factor 2; FM-MSC, fetal membrane-derived mesenchymal stem cell; GCP2, granulocyte chemoattractant protein 1; GF, growth factor; HLI, hind-limb ischemia; IM, intramuscular; iPSC-MSC, inducible pluripotent stem cell-derived mesenchymal stem cell; LV, left ventricle; MSC, mesenchymal stem cell; PGIS, prostacyclin synthase; TA, tibialis anterior; TV, tail vein; UCB-MSC, umbilical cord blood-derived mesenchymal stem cell.