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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.