Skip to main content

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

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
  1. ABI, ankle-brachial index; AT-MSC, adipose tissue-derived mesenchymal stem cell; BM-MNC, bone marrow mononuclear cell; BM-MSC, bone marrow-derived mesenchymal stem cell; DM, diabetes mellitus; M/B, muscle-tobrain (ratio); MRA, magnetic resonance angiography; MSC, mesenchymal stem cell; N/S, not significant; phosphate-buffered saline; TcO2, total carbon dioxide; UCB-MSC, umbilical cord blood-derived mesenchymal stem cell.
  2. *http://www.wongbakerfaces.org/