人间质基质/干细胞招募常驻周细胞并诱导血管成熟,以修复大鼠实验性脊髓损伤。
Human mesenchymal stromal/stem cells recruit resident pericytes and induce blood vessels maturation to repair experimental spinal cord injury in rats.
机构信息
Post-Graduate Program in Morphological Sciences, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Ave. Carlos Chagas Filho 373, Sala B1-011, Cidade Universitária, Ilha Do Fundão, Rio de Janeiro, RJ, 21941-590, Brazil.
Center for Regenerative Medicine, Petrópolis Faculty of Medicine, Av. Barão do Rio Branco 1003, Centro, Petrópolis, RJ, 25680-120, Brazil.
出版信息
Sci Rep. 2020 Nov 11;10(1):19604. doi: 10.1038/s41598-020-76290-0.
Angiogenesis is considered to mediate the beneficial effects of mesenchymal cell therapy in spinal cord injury. After a moderate balloon-compression injury in rats, injections of either human adipose tissue-derived stromal/stem cells (hADSCs) or their conditioned culture media (CM-hADSC) elicited angiogenesis around the lesion site. Both therapies increased vascular density, but the presence of hADSCs in the tissue was required for the full maturation of new blood vessels. Only animals that received hADSC significantly improved their open field locomotion, assessed by the BBB score. Animals that received CM-hADSC only, presented haemorrhagic areas and lack pericytes. Proteomic analyses of human angiogenesis-related factors produced by hADSCs showed that both pro- and anti-angiogenic factors were produced by hADSCs in vitro, but only those related to vessel maturation were detectable in vivo. hADSCs produced PDGF-AA only after insertion into the injured spinal cord. hADSCs attracted resident pericytes expressing NG2, α-SMA, PDGF-Rβ and nestin to the lesion, potentially contributing to blood vessel maturation. We conclude that the presence of hADSCs in the injured spinal cord is essential for tissue repair.
血管生成被认为介导了间充质细胞治疗脊髓损伤的有益作用。在大鼠中度气囊压迫损伤后,注射人脂肪组织来源的基质/干细胞(hADSCs)或其条件培养基(CM-hADSC)可在损伤部位周围引发血管生成。两种治疗方法都增加了血管密度,但组织中 hADSCs 的存在是新血管完全成熟所必需的。只有接受 hADSC 治疗的动物,其 BBB 评分才能显著改善其旷场运动能力。仅接受 CM-hADSC 治疗的动物出现了出血区域且缺乏周细胞。对 hADSCs 产生的与人血管生成相关的因子的蛋白质组学分析表明,hADSCs 在体外既能产生促血管生成因子,也能产生抗血管生成因子,但只有那些与血管成熟相关的因子在体内才能检测到。hADSCs 仅在插入损伤的脊髓后才会产生 PDGF-AA。hADSCs 吸引表达 NG2、α-SMA、PDGF-Rβ 和巢蛋白的固有周细胞到损伤部位,可能有助于血管成熟。我们的结论是,hADSCs 在损伤脊髓中的存在对于组织修复至关重要。