Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
PLoS One. 2012;7(2):e32815. doi: 10.1371/journal.pone.0032815. Epub 2012 Feb 28.
The delivery of bone marrow-derived cells (BMDCs) has been widely used to stimulate angiogenesis and arteriogenesis. We identified a progenitor-enriched subpopulation of BMDCs that is able to augment venular remodeling, a generally unexplored area in microvascular research. Two populations of BMDCs, whole bone marrow (WBM) and Lin(-)/Sca-1(+) progenitor cells, were encapsulated in sodium alginate and delivered to a mouse dorsal skinfold chamber model. Upon observation that encapsulated Sca-1(+) progenitor cells enhance venular remodeling, the cells and tissue were analyzed on structural and molecular levels. Venule walls were thickened and contained more nuclei after Sca-1(+) progenitor cell delivery. In addition, progenitors expressed mRNA transcript levels of chemokine (C-X-C motif) ligand 2 (CXCL2) and interferon gamma (IFNγ) that are over 5-fold higher compared to WBM. Tissues that received progenitors expressed significantly higher protein levels of vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and platelet derived growth factor-BB (PDGF-BB) compared to tissues that received an alginate control construct. Nine days following cell delivery, tissue from progenitor recipients contained 39% more CD45(+) leukocytes, suggesting that these cells may enhance venular remodeling through the modulation of the local immune environment. Results show that different BMDC populations elicit different microvascular responses. In this model, Sca-1(+) progenitor cell-derived CXCL2 and IFNγ may mediate venule enlargement via modulation of the local inflammatory environment.
骨髓来源细胞（BMDCs）的递送已被广泛用于刺激血管生成和动脉生成。我们鉴定了一种富含祖细胞的 BMDC 亚群，该亚群能够增强小静脉重塑，这是微血管研究中一个尚未被充分探索的领域。两种 BMDC 群体，即全骨髓（WBM）和 Lin(-)/Sca-1(+)祖细胞，被包裹在海藻酸钠中，并递送到小鼠背部皮肤囊腔模型中。观察到包裹的 Sca-1(+)祖细胞增强了小静脉重塑后，我们在结构和分子水平上分析了细胞和组织。Sca-1(+)祖细胞递送后，小静脉壁变厚且含有更多的核。此外，祖细胞表达趋化因子（C-X-C 基序）配体 2（CXCL2）和干扰素γ（IFNγ）的 mRNA 转录物水平比 WBM 高 5 倍以上。与接受藻酸盐对照构建体的组织相比，接受祖细胞的组织表达了显著更高水平的血管内皮生长因子（VEGF）、单核细胞趋化蛋白-1（MCP-1）和血小板衍生生长因子-BB（PDGF-BB）。细胞递送后 9 天，祖细胞接受者的组织中 CD45(+)白细胞增加了 39%，这表明这些细胞可能通过调节局部免疫环境来增强小静脉重塑。结果表明，不同的 BMDC 群体引发不同的微血管反应。在该模型中，Sca-1(+)祖细胞衍生的 CXCL2 和 IFNγ可能通过调节局部炎症环境介导小静脉扩大。
