Jabs Alexander, Moncada Gustavo A, Nichols Christopher E, Waller Edmund K, Wilcox Josiah N
Department of Hematology/Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
J Vasc Res. 2005 Mar-Apr;42(2):174-80. doi: 10.1159/000084406. Epub 2005 Mar 14.
Bone marrow-derived cell populations possess progenitor cell capacities. Emerging evidence also suggests significant plasticity of differentiated mononuclear cell lineages. We therefore assessed the distribution of transplanted peripheral blood mononuclear cells (PBMCs) in granulation tissue formation, and evaluated their possible transdifferentiation into myofibroblasts.
Silastic tubes were inserted into the peritoneal cavity of rats, followed by injection of PKH26-labelled PBMCs isolated from donor animals. At 3, 14 and 21 days, the distribution of PKH26(+) cells as well as their colocalization with myofibroblast/smooth muscle cell [alpha-smooth muscle (alpha-SM) actin] or macrophage markers (ED1/ED2) were determined.
Round-shaped PKH26(+) cells accumulated around the implants at 3 days, while myofibroblasts were rare. Later, peritoneal granulation tissue constituted an inner, multilayered capsule primarily comprising alpha-SM actin(+) cells that was surrounded by more loosely organized inflammatory connective tissue. PKH26-labelled, spindle-shaped cells were abundantly found in tissue capsules. As a key finding, granulation tissue at 14 and 21 days contained cells with both PKH26 and alpha-SM actin labelling. Accordingly, a subpopulation of cells staining positive for macrophage markers showed a spindle-shaped morphology and alpha-SM actin expression.
Transplanted PBMCs contribute to granulation tissue, and acquire myofibroblast characteristics during de novo tissue formation. Mononuclear cells may transdifferentiate into myofibroblast-like cells within an inflammatory environment.
骨髓来源的细胞群体具有祖细胞能力。新出现的证据还表明分化的单核细胞谱系具有显著的可塑性。因此，我们评估了移植的外周血单个核细胞（PBMC）在肉芽组织形成中的分布，并评估了它们可能向肌成纤维细胞的转分化情况。
将硅橡胶管插入大鼠腹腔，随后注射从供体动物分离的PKH26标记的PBMC。在第3、14和21天，确定PKH26(+)细胞的分布及其与肌成纤维细胞/平滑肌细胞[α-平滑肌（α-SM）肌动蛋白]或巨噬细胞标志物（ED1/ED2）的共定位情况。
圆形的PKH26(+)细胞在3天时聚集在植入物周围，而肌成纤维细胞很少见。后来，腹膜肉芽组织形成一个内部的多层包膜，主要由α-SM肌动蛋白(+)细胞组成，周围是组织较疏松的炎性结缔组织。在组织包膜中大量发现了PKH26标记的梭形细胞。一项关键发现是，在第14天和21天的肉芽组织中含有同时被PKH26和α-SM肌动蛋白标记的细胞。因此，一群巨噬细胞标志物染色呈阳性的细胞呈现梭形形态并表达α-SM肌动蛋白。
移植的PBMC有助于肉芽组织形成，并在新生组织形成过程中获得肌成纤维细胞特征。单核细胞可能在炎性环境中转分化为肌成纤维细胞样细胞。
