From: Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia
Reference | Treatment | MSC recipients | Outcome |
---|---|---|---|
Kim et al., 2006 [82] | Intramuscular administration of allogeneic UCB-MSCs into proximal and around the necrotic lesion(s) (1 × 106 cells per lesion) | Buerger's disease (n = 4) | 1. Increased collateral branches and vascularities in foot based on angiography |
 | Note: |  | 2. Resolution of rest pain as early as 5 hours |
 | 1. Two patients received repeated UCB-MSCs approximately 1 year apart. |  | 3. Complete healing of necrotic lesion within 120 days |
 | 2. One patient received BM-MSCs 6 months prior to UCB-MSC administration. |  |  |
Dash et al., 2009 [84] | Intramuscular and topical autologous BM-MSCs (>1 × 106 cells/cm2 of ulcer area): | Buerger's disease (n = 9) | At 12 weeks as compared with baseline: |
 | Buerger's disease: angiographically selected sites in soleus and gastrocnemius, popliteal fossa and ulcer area | Diabetic foot (n = 3) | 1. Pain relief |
 | Diabetic foot: around ulcer area |  | 2. Reduction in ulcer size |
 |  |  | 3. Increased pain-free walking distance: 38.33 ± 17.86 m to 284.44 ± 212.12 m (P <0.001) |
Guiducci et al., 2010 [85] | Three intravenous administrations of autologous BM-MSCs: | Systemic sclerosis (n = 1) | At 2 months as compared with baseline: |
 | 1. 0.9 × 106 cells/kg (month 0): cryopreserved cells at passage 1 |  | 1. Reduction in skin necrosis |
 | 2. 0.8 × 106 cells/kg (month 1): culture-expanded at passage 2 |  | 2. Formation of new vessel network and improved blood flow in both the upper and lower limbs based on angiography |
 | 3. 0.8 × 106 cells/kg (month 2): culture-expanded at passage 2 |  |  |
Lu et al., 2011 [88] | Group A: Ipsilateral limb received a total of 9.3 ± 1.1 × 108 BM-MSCs and contralateral limb received N/S (n = 18) | Type 2 DM with foot ulcer, Fontaine IV (n = 18) | At 24 weeks as compared with baseline (BM-MSCs versus N/S): |
 | Group B: Ipsilateral limb received a total of 9.6 ± 1.1 × 108 BM-MNCs and contralateral limb received N/S (n = 19) |  | 1. Improved in rest pain |
 | Note: 20 intramuscular injections administered at the foot ulcer and surrounding areas (3 × 3 cm intervals) |  | 2. Improved in pain-free walking time |
 |  |  | 3. Improved ABI |
 |  |  | 4. Improved TcO2 |
 |  |  | 5. Increased collateral vessels based on MRA |
 |  |  | 6. Improved ulcer healing rate |
 |  |  | 7. Reduced limb amputation |
Lasala et al., 2010 [86] | Ipsilateral limb received a total of 30 × 106 autologous BM-MSCs and 30 × 108 autologous BM-MNCs and contralateral limb received PBS and 5% human serum albumin | DM, Fontaine IIb-IV (n = 10) | At 10 ± 2 months as compared with baseline: |
 |  |  | 1. Improved ABI as early as 1 month after infusion |
 |  |  | 2. Improved walking time |
 | Note: 40 intramuscular injections administered at the most hypoperfused areas of the gastrocnemius (based on digital angiography) |  | At 6 months as compared with baseline: |
 |  |  | 1. Improved quality of life (pain relief and physical functioning) |
 |  |  | 2. Improved new collateral vessel formation based on digital subtraction angiography |
 |  |  | 3. Improved limb perfusion based on 99mTc-TF perfusion scintigraphy |
Lasala et al., 2011 [87] | Group A: Ipsilateral limb received a total of 9 × 106 autologous BM-MSCs and 9 × 108 autologous BM-MNCs and contralateral limb received PBS + 5% human serum albumin (n = 12) | DM, Rutherford 4-6 (n = 26) | At 4 months as compared with baseline: |
 | Group B: Ipsilateral limb received a total of 18 × 106 autologous BM-MSCs and 18 × 108 autologous BM-MNCs and contralateral limb received PBS with 5% human serum albumin (n = 14) |  | 1. Improved ABI (n = 21) in the index leg |
 | Note: 40 intramuscular injections administered at the most hypoperfused areas of the gastrocnemius (based on digital angiography) |  | 2. Improved pain-free walking time as early as 2 weeks |
 |  |  | 3. Improved quality of life (pain relief and improvement of physical functioning) |
 |  |  | 5. Improved limb perfusion |
 |  |  | 6. Complete healing of chronic ischemic ulcers |
Lee et al., 2012 [89] | Ipsilateral limb received a total of 3 × 108 autologous AT-MSCs | Buerger's disease, Rutherford II-4 to III-6 (n = 12) | At 6 months as compared with baseline: |
 | Note: 60 intramuscular injections to lower limb (5 × 106 AT-MSCs each) | Diabetic foot, Rutherford III-5 to III-6 (n = 3) | 1. Improved Wong-Baker FACES* pain rating score |
 |  |  | 2. Improved claudication walking distance |
 |  |  | 3. Improved maximal walking distance (not statistically significant) |
 |  |  | 4. No change in ABI |
 |  |  | 5. Improved in temperature color change (thermography) |
 |  |  | 6. Improved in collateral vessel formation using digital subtraction angiography |
 |  |  | 7. Improved wound healing and clinical symptoms |