Cell therapy in critical limb ischemia: A comprehensive analysis of two cell therapy products

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• 作者：Claire Tournois¹ ; ² ; Bernard Pignon³ ; Marie-Antoinette Sevestre⁴ ; Rida Al-Rifai² ; Valerie Creuza¹ ; Ga&euml ; l Poitevin² ; Caroline Franç ; ois² ; Philippe Nguyen¹ ; ² ; ^{pnguyen@chu-reims.fr}
• 关键词：angiogenesis ; cell therapy ; critical limb ischemia ; endothelial progenitor cells ; mesenchymal stem cells ; transcriptome
• 刊名：Cytotherapy
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：19
• 期：2
• 页码：299-310
• 全文大小：1524 K
• 卷排序：19

文摘

Cell therapy has been proposed as a salvage limb procedure in critical limb ischemia (CLI). In spite of the fact that clinical trials found some efficacy, the mechanism of action remains elusive. The objective of this study was to characterize two autologous cell therapy products (CTPs) obtained from patients with advanced peripheral arterial disease.MethodsBone marrow (BM-CTPs) (n = 20) and CTPs obtained by non-mobilized cytapheresis (peripheral blood [PB]-CTPs) (n = 20) were compared. CTPs were characterized by their cell composition, by the quantification of endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs) and by transcriptomic profiling. The angiogenic profile and the 6-month outcome of CLI patients are described.ResultsPatients presented inflammation syndrome and high levels of CXCL12, soluble stem cell factor and granulocyte colony-stimulating factor, whereas granulocyte macrophage colony-stimulating factor was low. Circulating CD34+ cells represented rare events. BM and PB-CTPs were heterogeneous. Mature cells and colony-forming unit–endothelial cells were in higher concentration in PB-CTPs, whereas CD34+ stem cells and EPCs were more abundant in BM-CTPs. MSCs were identified in both CTPs. Transcriptomic profiling revealed the strong angiogenic potential of BM-CTPs. Transcutaneous partial pressure of oxygen, C-reative protein and neutrophil content in CTPs are predictive of the clinical outcome at 6 months.DiscussionTranscriptomic allows an accurate characterization of CTPs. BM-CTPs have the richest content in terms of stem cells and transcriptome. The high content of mature cells in PB-CTPs means that they work via a paracrine mechanism. The clinical outcome indicates the deleterious influence the patients' status and the limits of an autologous approach. In this respect, MSCs may allow an allogenic strategy.