Injury mechanism dictates contribution of bone marrow-derived cells to murine hepatic vascular regeneration
Injury mechanism dictates contribution of bone marrow-derived cells to murine hepatic vascular regeneration
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DOI：
10.1203/pdr.0b013e31815b481c
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发表时间：
2008-02-01
影响因子：
3.6
通讯作者：
Hirschi, Karen K.
中科院分区：
文献类型：
--
作者：
Kienstra, Kirsten A.;Jackson, Kathyjo A.;Hirschi, Karen K.
来自成人骨髓的干细胞和祖细胞已被证明可以再生血管细胞以应对损伤。然而，目前还不清楚损伤的类型是否决定了这些细胞对新血管形成的贡献，以及哪些细胞亚群有助于血管再生。为了解决这些问题，我们确定了造血干细胞（HSC）在两种类型的肝损伤（部分肝切除术（PH）和毒素诱导的损伤）中促进血管形成的程度。将Lac-Z标记的HSC移植到致死性照射的遗传匹配的受体中。14天后，我们确定了移植的细胞植入内毒素损伤的肝脏血管内皮细胞，但不是在响应PH再生的肝脏血管系统。植入的HSC衍生的细胞发生在一个梯度的方式与最高的活动在严重受伤的地区。尽管HSC来源的细胞对微血管和大血管都有贡献，但大口径血管倾向于更高的植入水平。因此，骨髓来源的细胞对肝脏新生血管的贡献取决于持续损伤的类型。此外，在毒素诱导的肝损伤后，与毛细血管相比，大血管中的植入率倾向于更高，这表明相对于新微血管的形成，现有血管的重塑是修复的主要机制。
Stem and progenitor cells derived from adult marrow have been shown to regenerate vascular cells in response to injury. However, it is unclear whether the type of injury dictates the contribution of such cells to neovascularization and which subpopulations of cells contribute to vascular regeneration. To address these questions, we determined the extent that hematopoietic stem cells (HSC) contributed to blood vessel formation in response to two types of liver injury, partial hepatectomy (PH) and toxin-induced injury. Lac-Z-labeled HSC were engrafted into lethally irradiated, genetically matched recipients. After 14 d, we identified transplanted cells engrafted within the vascular endothelium of toxin-damaged liver, but not in the vasculature of liver regenerated in response to PH. Engraftment of HSC-derived cells occurred in a gradient fashion with the highest activity in the severely injured areas. Although HSC-derived cells contributed to both microvessels and large vessels, the large caliber vessels trended toward higher engraftment levels. Thus, the contribution of marrow-derived cells to hepatic neovascularization is dependent upon the type of injury sustained. Furthermore, following toxin-induced liver injury, engraftment rates trended higher in large vessels compared with capillaries, suggesting that remodeling of existing vessels is a predominant mechanism of repair, relative to the formation of new microvasculature.