Beer Lucian, Mildner Michael, Gyöngyösi Mariann, Ankersmit Hendrik Jan
Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
Apoptosis. 2016 Dec;21(12):1336-1353. doi: 10.1007/s10495-016-1292-8.
For almost two decades, cell-based therapies have been tested in modern regenerative medicine to either replace or regenerate human cells, tissues, or organs and restore normal function. Secreted paracrine factors are increasingly accepted to exert beneficial biological effects that promote tissue regeneration. These factors are called the cell secretome and include a variety of proteins, lipids, microRNAs, and extracellular vesicles, such as exosomes and microparticles. The stem cell secretome has most commonly been investigated in pre-clinical settings. However, a growing body of evidence indicates that other cell types, such as peripheral blood mononuclear cells (PBMCs), are capable of releasing significant amounts of biologically active paracrine factors that exert beneficial regenerative effects. The apoptotic PBMC secretome has been successfully used pre-clinically for the treatment of acute myocardial infarction, chronic heart failure, spinal cord injury, stroke, and wound healing. In this review we describe the benefits of choosing PBMCs instead of stem cells in regenerative medicine and characterize the factors released from apoptotic PBMCs. We also discuss pre-clinical studies with apoptotic cell-based therapies and regulatory issues that have to be considered when conducting clinical trials using cell secretome-based products. This should allow the reader to envision PBMC secretome-based therapies as alternatives to all other forms of cell-based therapies.
近二十年来，基于细胞的疗法一直在现代再生医学中进行测试，以替代或再生人类细胞、组织或器官，并恢复正常功能。分泌的旁分泌因子越来越被认为能发挥促进组织再生的有益生物学效应。这些因子被称为细胞分泌组，包括多种蛋白质、脂质、微小RNA以及细胞外囊泡，如外泌体和微粒。干细胞分泌组最常在前临床环境中进行研究。然而，越来越多的证据表明，其他细胞类型，如外周血单核细胞（PBMC），能够释放大量具有生物活性的旁分泌因子，发挥有益的再生作用。凋亡的PBMC分泌组已在前临床中成功用于治疗急性心肌梗死、慢性心力衰竭、脊髓损伤、中风和伤口愈合。在本综述中，我们描述了在再生医学中选择PBMC而非干细胞的益处，并对凋亡PBMC释放的因子进行了表征。我们还讨论了基于凋亡细胞疗法的临床前研究以及在使用基于细胞分泌组的产品进行临床试验时必须考虑的监管问题。这应能让读者将基于PBMC分泌组的疗法视为所有其他形式基于细胞疗法的替代方案。
