Table 4 Summary of the current published data on mesenchymal stem cell-based therapy for critical limb ischemia

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