Pacini Simone, Barachini Serena, Montali Marina, Carnicelli Vittoria, Fazzi Rita, Parchi Paolo, Petrini Mario
1 Hematology Division, Department of Clinical and Experimental Medicine, University of Pisa , Pisa, Italy .
2 Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa , Pisa, Italy .
Stem Cells Dev. 2016 May 1;25(9):661-73. doi: 10.1089/scd.2015.0344. Epub 2016 Apr 11.
Mesenchymal stromal cells (MSCs) have been the object of extensive research for decades, due to their intrinsic clinical value. Nonetheless, the unambiguous identification of a unique in vivo MSC progenitor is still lacking, and the hypothesis that these multipotent cells could possibly arise from different in vivo precursors has been gaining consensus in the last years. We identified a novel multipotent cell population in human adult bone marrow that we first named Mesodermal Progenitor Cells (MPCs) for the ability to differentiate toward the mesenchymal lineage, while still retaining angiogenic potential. Despite extensive characterization, MPCs positioning within the differentiation pathway and whether they can be ascribed as possible distinctive progenitor of the MSC lineage is still unclear. In this study, we describe the ex vivo isolation of one novel bone marrow subpopulation (Pop#8) with the ability to generate MPCs. Multicolor flow cytometry in combination with either fluorescence-activated cell sorting or magnetic-activated cell sorting were applied to characterize Pop#8 as CD64(bright)CD31(bright)CD14(neg). We defined Pop#8 properties in culture, including the potential of Pop#8-derived MPCs to differentiate into MSCs. Gene expression data were suggestive of Pop#8 in vivo involvement in hematopoietic stem cell niche constitution/maintenance. Pop#8 resulted over three logs more frequent than other putative MSC progenitors, corroborating the idea that most of the controversies regarding culture-expanded MSCs could be the consequence of different culture conditions that select or promote particular subpopulations of precursors.
几十年来,间充质基质细胞(MSCs)一直是广泛研究的对象,因为它们具有内在的临床价值。然而,目前仍缺乏对体内独特的MSC祖细胞的明确鉴定,并且这些多能细胞可能源自不同体内前体的假说在过去几年中已逐渐得到认可。我们在成人骨髓中鉴定出一种新型多能细胞群体,由于其向间充质谱系分化的能力,同时仍保留血管生成潜力,我们最初将其命名为中胚层祖细胞(MPCs)。尽管进行了广泛的表征,但MPCs在分化途径中的定位以及它们是否可被归为MSC谱系可能的独特祖细胞仍不清楚。在本研究中,我们描述了一种具有产生MPCs能力的新型骨髓亚群(Pop#8)的体外分离。应用多色流式细胞术结合荧光激活细胞分选或磁激活细胞分选将Pop#8表征为CD64(bright)CD31(bright)CD14(neg)。我们定义了Pop#8在培养中的特性,包括Pop#8来源的MPCs分化为MSCs的潜力。基因表达数据表明Pop#8在体内参与造血干细胞龛的构成/维持。Pop#8的出现频率比其他假定的MSC祖细胞高出三个对数以上,这证实了关于培养扩增的MSCs的大多数争议可能是由于选择或促进特定前体亚群的不同培养条件所致的观点。