BACKGROUND: Mononuclear cells contain progenitor cells including haematopoietic and mesenchymal stem cells, endothelial progenitor cells and fibroblasts which facilitate wound healing through cytokines, growth factor secretions, cell-cell interactions and provision of extracellular matrix scaffolding. Clinical applications of autologous mononuclear cells therapy in wound healing in non-malignant patients with critical limb ischaemia have been reported with remarkable outcome.
METHODS: We report three patients with haematological malignancies undergoing chemotherapy, who received autologous mononuclear cells implantation to treat non-healing wound after optimum conventional wound care. The sources of mononuclear cells (MNC) were from bone marrow (BM), peripheral blood (PB) and mobilised PB cells (mPB-MNC) using granulocyte colony stimulating factor (G-CSF). The cells were directly implanted into wound and below epidermis. Wound sizes and adverse effects from implantation were assessed at regular intervals.
RESULTS: All patients achieved wound healing within three months following autologous mononuclear cells implantation. No implantation adverse effects were observed.
CONCLUSIONS: Autologous mononuclear cells therapy is a feasible alternative to conventional wound care to promote complete healing in non-healing wounds compounded by morbid factors such as haematological malignancies, chemotherapy, diabetes mellitus (DM), infections and prolonged immobility.
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.
RECENT FINDINGS: The total number of personalised external aortic root support (PEARS) operations is now approaching 700 in 30 centres in Australia, Belgium, Brazil, Czech Republic, Great Britain, Greece, Ireland, Malaysia, Netherlands, New Zealand, Poland and Slovakia. There are continued reports of stability of aortic dimensions and aortic valve function with the only exceptions known being where the surgeon has deviated from the instructions for use of the device. The median root diameter of Marfan patients having PEARS was 47 mm suggesting that the existing criterion of 50 mm is due for reconsideration. The peri-operative mortality currently estimated to be less than 0.3%. The first recipient remains alive and well after 18 years. The use of PEARS as an adjunct to the Ross operation to support the pulmonary autograft is being explored in several centres.
SUMMARY: The operation requires proctoring and adherence to a strict operative protocol and with those precautions excellent results are attained. The evidence and opinions provided in the cited publications indicate that PEARS is a proven and successful prophylactic operation for aortic root aneurysm.
METHODS: Literature search was performed to identify all level I and II studies reporting the clinical and structural outcome of any ACI generation in human knees using the following medical electronic databases: PubMed, EMBASE, Cochrane Library, CINAHL, SPORTDiscus and NICE healthcare database. The level of evidence, sample size calculation and risk of bias were determined for all included studies to enable quality assessment.
RESULTS: Twenty studies were included in the analysis, reporting on a total of 1094 patients. Of the 20 studies, 13 compared ACI with other treatment modalities, seven compared different ACI cell delivery methods, and one compared different cell source for implantation. Studies included were heterogeneous in baseline design, preventing meta-analysis. Data showed a trend towards similar outcomes when comparing ACI generations with other repair techniques and when comparing different cell delivery methods and cell source selection. Majority of the studies (80 %) were level II evidence, and overall the quality of studies can be rated as average to low, with the absence of power analysis in 65 % studies.
CONCLUSION: At present, there are insufficient data to conclude any superiority of ACI techniques. Considering its two-stage operation and cost, it may be appropriate to reserve ACI for patients with larger defects or those who have had inadequate response to other repair procedures until hard evidence enables specific clinical recommendations be made.
LEVEL OF EVIDENCE: II.