Abstract
Background: Revascularisation therapy is the current gold standard of care for critical limb ischemia (CLI), although a significant proportion of patients with CLI either are not fit for or do not respond well to this procedure. Recently, novel angiogenic therapies such as the use of autologous cell-based therapy (CBT) have been examined, but the results of individual trials were inconsistent. Objective: To pool all published studies that compared the safety and efficacy of autologous CBT derived from different sources and phenotypes with non cell-based therapy (NCT) in CLI patients. Methods: We searched Medline, Embase, Cochrane Library and ClinicalTrials.gov from 1974-2017. Sixteen randomised clinical trials (RCTs) involving 775 patients receiving the following interventions: mobilised peripheral blood stem cells(m-PBSC), bone marrow mononuclear cells(BM-MNC), bone marrow mesenchymal stem cells(BM-MSC), cultured BM-MNC(Ixmyelocel-T), cultured PB cells(VesCell) and CD34+ cells were included in the meta-analysis. Results: High-quality evidence (QoE) showed similar all-cause mortality rates between CBT and NCT. AR reduction by approximately 60% were observed in patients receiving CBT compared to NCT (moderate QoE). CBT patients experienced improvement in ulcer healing, ABI, TcO2, pain free walking capacity and collateral vessel formation (moderate QoE). Low-to-moderate QoE showed that compared to NCT, intramuscular BM-MNC and m-PBSC may reduce amputation rate, rest pain, and improve ulcer healing and ankle-brachial pressure index, while intramuscular BM-MSC appeared to improve rest pain, ulcer healing and pain-free walking distance but not AR. Efficacy of other types of CBT could not be confirmed due to limited data. Cell harvesting and implantation appeared safe and well-tolerated with similar rates of adverse-events between groups. Conclusion: Implantation of autologous CBT may be an effective therapeutic strategy for no-option CLI patients. BM-MNC and m-PSBC appear more effective than NCT in improving AR and other limb perfusion parameters. BM-MSC may be beneficial in improving perfusion parameters but not AR, however, this observation needs to be confirmed in a larger population of patients. Generally, treatment using various sources and phenotypes of cell products appeared safe and well tolerated. Large-size RCTs with long follow-up are warranted to determine the superiority and durability of angiogenic potential of a particular CBT and the optimal treatment regimen for CLI.
| Original language | English |
|---|---|
| Pages (from-to) | 265-283 |
| Number of pages | 19 |
| Journal | Current Stem Cell Research and Therapy |
| Volume | 13 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1 May 2018 |
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Keywords
- Amputation
- Bone marrow mesenchymal stem cells (BM-MSC)
- Bone marrow mononuclear cells (BM-MNC)
- Cell-based therapy (CBT)
- Critical limb ischemia (CLI)
- Mobilized peripheral blood stem cells (m-PBSC)
- Non cell-based therapy (NCT)
ASJC Scopus subject areas
- Medicine (miscellaneous)
Cite this
Efficacy and safety of autologous cell-based therapy in patients with no-option critical limb ischaemia : A meta-analysis. / S. Abdul Wahid, S Fadilah; Ismail, Nor Azimah; Jamaludin, Wan Fariza Wan; Muhamad, Nor Asiah; Md Idris, Mohamad Azim; Lai, Nai Ming.
In: Current Stem Cell Research and Therapy, Vol. 13, No. 4, 01.05.2018, p. 265-283.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Efficacy and safety of autologous cell-based therapy in patients with no-option critical limb ischaemia
T2 - A meta-analysis
AU - S. Abdul Wahid, S Fadilah
AU - Ismail, Nor Azimah
AU - Jamaludin, Wan Fariza Wan
AU - Muhamad, Nor Asiah
AU - Md Idris, Mohamad Azim
AU - Lai, Nai Ming
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Background: Revascularisation therapy is the current gold standard of care for critical limb ischemia (CLI), although a significant proportion of patients with CLI either are not fit for or do not respond well to this procedure. Recently, novel angiogenic therapies such as the use of autologous cell-based therapy (CBT) have been examined, but the results of individual trials were inconsistent. Objective: To pool all published studies that compared the safety and efficacy of autologous CBT derived from different sources and phenotypes with non cell-based therapy (NCT) in CLI patients. Methods: We searched Medline, Embase, Cochrane Library and ClinicalTrials.gov from 1974-2017. Sixteen randomised clinical trials (RCTs) involving 775 patients receiving the following interventions: mobilised peripheral blood stem cells(m-PBSC), bone marrow mononuclear cells(BM-MNC), bone marrow mesenchymal stem cells(BM-MSC), cultured BM-MNC(Ixmyelocel-T), cultured PB cells(VesCell) and CD34+ cells were included in the meta-analysis. Results: High-quality evidence (QoE) showed similar all-cause mortality rates between CBT and NCT. AR reduction by approximately 60% were observed in patients receiving CBT compared to NCT (moderate QoE). CBT patients experienced improvement in ulcer healing, ABI, TcO2, pain free walking capacity and collateral vessel formation (moderate QoE). Low-to-moderate QoE showed that compared to NCT, intramuscular BM-MNC and m-PBSC may reduce amputation rate, rest pain, and improve ulcer healing and ankle-brachial pressure index, while intramuscular BM-MSC appeared to improve rest pain, ulcer healing and pain-free walking distance but not AR. Efficacy of other types of CBT could not be confirmed due to limited data. Cell harvesting and implantation appeared safe and well-tolerated with similar rates of adverse-events between groups. Conclusion: Implantation of autologous CBT may be an effective therapeutic strategy for no-option CLI patients. BM-MNC and m-PSBC appear more effective than NCT in improving AR and other limb perfusion parameters. BM-MSC may be beneficial in improving perfusion parameters but not AR, however, this observation needs to be confirmed in a larger population of patients. Generally, treatment using various sources and phenotypes of cell products appeared safe and well tolerated. Large-size RCTs with long follow-up are warranted to determine the superiority and durability of angiogenic potential of a particular CBT and the optimal treatment regimen for CLI.
AB - Background: Revascularisation therapy is the current gold standard of care for critical limb ischemia (CLI), although a significant proportion of patients with CLI either are not fit for or do not respond well to this procedure. Recently, novel angiogenic therapies such as the use of autologous cell-based therapy (CBT) have been examined, but the results of individual trials were inconsistent. Objective: To pool all published studies that compared the safety and efficacy of autologous CBT derived from different sources and phenotypes with non cell-based therapy (NCT) in CLI patients. Methods: We searched Medline, Embase, Cochrane Library and ClinicalTrials.gov from 1974-2017. Sixteen randomised clinical trials (RCTs) involving 775 patients receiving the following interventions: mobilised peripheral blood stem cells(m-PBSC), bone marrow mononuclear cells(BM-MNC), bone marrow mesenchymal stem cells(BM-MSC), cultured BM-MNC(Ixmyelocel-T), cultured PB cells(VesCell) and CD34+ cells were included in the meta-analysis. Results: High-quality evidence (QoE) showed similar all-cause mortality rates between CBT and NCT. AR reduction by approximately 60% were observed in patients receiving CBT compared to NCT (moderate QoE). CBT patients experienced improvement in ulcer healing, ABI, TcO2, pain free walking capacity and collateral vessel formation (moderate QoE). Low-to-moderate QoE showed that compared to NCT, intramuscular BM-MNC and m-PBSC may reduce amputation rate, rest pain, and improve ulcer healing and ankle-brachial pressure index, while intramuscular BM-MSC appeared to improve rest pain, ulcer healing and pain-free walking distance but not AR. Efficacy of other types of CBT could not be confirmed due to limited data. Cell harvesting and implantation appeared safe and well-tolerated with similar rates of adverse-events between groups. Conclusion: Implantation of autologous CBT may be an effective therapeutic strategy for no-option CLI patients. BM-MNC and m-PSBC appear more effective than NCT in improving AR and other limb perfusion parameters. BM-MSC may be beneficial in improving perfusion parameters but not AR, however, this observation needs to be confirmed in a larger population of patients. Generally, treatment using various sources and phenotypes of cell products appeared safe and well tolerated. Large-size RCTs with long follow-up are warranted to determine the superiority and durability of angiogenic potential of a particular CBT and the optimal treatment regimen for CLI.
KW - Amputation
KW - Bone marrow mesenchymal stem cells (BM-MSC)
KW - Bone marrow mononuclear cells (BM-MNC)
KW - Cell-based therapy (CBT)
KW - Critical limb ischemia (CLI)
KW - Mobilized peripheral blood stem cells (m-PBSC)
KW - Non cell-based therapy (NCT)
UR - http://www.scopus.com/inward/record.url?scp=85046719439&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046719439&partnerID=8YFLogxK
U2 - 10.2174/1574888X13666180313141416
DO - 10.2174/1574888X13666180313141416
M3 - Review article
VL - 13
SP - 265
EP - 283
JO - Current Stem Cell Research and Therapy
JF - Current Stem Cell Research and Therapy
SN - 1574-888X
IS - 4
ER -