Autologous cells derived from different sources and administered using different regimens for 'no‐option' critical lower limb ischaemia patients

摘要: Background Revascularisation is the gold standard therapy for patients with critical limb ischaemia (CLI). In over 30% of who are not suitable or have failed previous revascularisation (the 'no-option' CLI patients), amputation eventually unavoidable. Preliminary studies reported encouraging outcomes autologous cell-based treatment in these patients. However, comparing angiogenic potency and clinical effects cells derived from different sources yielded limited data. Data regarding cell doses routes administration also limited. Objectives To compare efficacy safety sources, prepared using protocols, administered at doses, delivered via Search methods The Cochrane Vascular Information Specialist (CIS) searched Specialised Register, Central Register Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Cumulative Index to Nursing Allied Health Literature (CINAHL), Complementary Medicine Database (AMED), trials registries (16 May 2018). Review authors PubMed until February 2017. Selection criteria We included randomised controlled (RCTs) involving a particular source regimen against another therapy. collection analysis Three review independently assessed eligibility methodological quality trials. extracted outcome data each trial pooled them meta-analysis. calculated effect estimates risk ratio (RR) 95% confidence interval (CI), mean difference (MD) CI. Main results seven RCTs total 359 participants. These compared bone marrow-mononuclear (BM-MNCs) versus mobilised peripheral blood stem (mPBSCs), BM-MNCs marrow-mesenchymal (BM-MSCs), high dose low dose, intramuscular (IM) intra-arterial (IA) implantation. identified no other comparisons studies. considered most be bias random sequence generation, incomplete data, selective reporting; blinding personnel; unclear allocation concealment assessors. evidence was often very low, bias, imprecision, indirectness major downgrading factors.Three (100 participants) nine deaths during study follow-up period. did report according group.Results show clear rates between IM IA (RR 0.80, CI 0.54 1.18; three RCTs, 95 participants; low-quality evidence). Single-study BM-MNC- mPBSC-treated groups 1.54, 0.45 5.24; 150 evidence) 3.21, 0.87 11.90; 16 BM-MSCs amputations.Single-study similar numbers participants healing ulcers mPBSCs 0.89, 0.44 1.83; 49 1.13, 0.73 1.76; 41 participants). contrast, more appeared BM-MSC group than BM-MNC 2.00, 1.02 3.92; one RCT, 22 moderate-quality Researchers ulcer healing.Single-study reduction rest pain 0.99, 0.93 1.06; 104 1.22, 0.91 1.64; 32 One scores (MD 0.00, -0.61 0.61; 37 pain.Single-study number increased ankle-brachial index (ABI; increase > 0.1 pretreatment), 1.00, 0.71 1.40; evidence), 0.93, 0.43 2.00; 35 ABI higher 0.05, 0.01 0.09; comparison.Similar had improved transcutaneous oxygen tension (TcO₂) 0.86 1.72; two 62 TcO₂ reading 8.00, 3.46 12.54; mPBSC- BM-MNC-treated 1.70, 0.41 2.99; comparison.Study significant short-term adverse attributed Authors' conclusions Mostly low- suggests differences regimens implantation such as all-cause mortality, rate, healing, Pooled analyses whether were routes. High-quality lacking; therefore long-term patients, remain confirmed.Future larger needed determine along optimal source, phenotype, route Longer confirm durability potential