Efficacy and safety of autologous  cell-based therapy in patients  with no-option critical limb ischaemia

A meta-analysis

S Fadilah S. Abdul Wahid, Nor Azimah Ismail, Wan Fariza Wan Jamaludin, Nor Asiah Muhamad, Mohamad Azim Md Idris, Nai Ming Lai

Research output: Contribution to journalReview article

4 Citations (Scopus)

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 languageEnglish
Pages (from-to)265-283
Number of pages19
JournalCurrent Stem Cell Research and Therapy
Volume13
Issue number4
DOIs
Publication statusPublished - 1 May 2018

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Cell- and Tissue-Based Therapy
Meta-Analysis
Ischemia
Extremities
Safety
Bone Marrow Cells
Mesenchymal Stromal Cells
Ulcer
Bone Marrow
Walking
Cultured Cells
Randomized Controlled Trials
Perfusion
Phenotype
Therapeutics
Pain
Ankle Brachial Index
Standard of Care
Amputation
Libraries

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 journalReview article

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title = "Efficacy and safety of autologous  cell-based therapy in patients  with no-option critical limb ischaemia: A meta-analysis",
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.",
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)",
author = "{S. Abdul Wahid}, {S Fadilah} and Ismail, {Nor Azimah} and Jamaludin, {Wan Fariza Wan} and Muhamad, {Nor Asiah} and {Md Idris}, {Mohamad Azim} and Lai, {Nai Ming}",
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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)

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DO - 10.2174/1574888X13666180313141416

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