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首页> 外文期刊>International Journal of Molecular Sciences >Cell Sheets from Adipose Tissue MSC Induce Healing of Pressure Ulcer and Prevent Fibrosis via Trigger Effects on Granulation Tissue Growth and Vascularization
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Cell Sheets from Adipose Tissue MSC Induce Healing of Pressure Ulcer and Prevent Fibrosis via Trigger Effects on Granulation Tissue Growth and Vascularization

机译:来自脂肪组织MSC的细胞片诱导压力溃疡的愈合,并通过触发对造粒组织生长和血管形成的触发效应进行纤维化

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We report a comparative study of multipotent mesenchymal stromal cells (MSC) delivered by injection, MSC-based cell sheets (CS) or MSC secretome to induce healing of cutaneous pressure ulcer in C57Bl/6 mice. We found that transplantation of CS from adipose-derived MSC resulted in reduction of fibrosis and recovery of skin structure with its appendages (hair and cutaneous glands). Despite short retention of CS on ulcer surface (3–7 days) it induced profound changes in granulation tissue (GT) structure, increasing its thickness and altering vascularization pattern with reduced blood vessel density and increased maturation of blood vessels. Comparable effects on GT vascularization were induced by MSC secretome, yet this treatment has failed to induce repair of skin with its appendages we observed in the CS group. Study of secretome components produced by MSC in monolayer or sheets revealed that CS produce more factors involved in pericyte chemotaxis and blood vessel maturation (PDGF-BB, HGF, G-CSF) but not sprouting inducer (VEGF165). Analysis of transcriptome using RNA sequencing and Gene Ontology mapping found in CS upregulation of proteins responsible for collagen binding and GT maturation as well as fatty acid metabolism enzymes known to be negative regulators of blood vessel sprouting. At the same time, downregulated transcripts were enriched by factors activating capillary growth, suggesting that in MSC sheets paracrine activity may shift towards matrix remodeling and maturation of vasculature, but not activation of blood vessel sprouting. We proposed a putative paracrine trigger mechanism potentially rendering an impact on GT vascularization and remodeling. Our results suggest that within sheets, MSC may change their functional state and spectrum of soluble factors that influence tissue repair and induce more effective skin healing inclining towards regeneration and reduced scarring.
机译:我们报告了通过注射,基于MSC的细胞片(CS)或MSC沉淀,以诱导C57BL / 6小鼠中皮肤压力溃疡的愈合递送的多能的间充质基质细胞(MSC)的比较研究。我们发现将CS移植来自脂肪衍生的MSC导致纤维化和皮肤结构恢复的纤维化和伴随(头发和皮肤腺体)导致。尽管在溃疡表面(3-7天)的含量短暂保留(3-7天),它诱导肉芽组织(GT)结构的深刻变化,增加其厚度和改变血管密度降低和血管成熟增加的血管形成。通过MSC沉淀诱导GT血管化对GT血管化的相当效果,但这种治疗未能在CS组中观察到的附属物,未诱导皮肤修复。 MSC在单层或片材中产生的沉菌组分揭示了CS产生更多的因素,涉及周围趋化性和血管成熟(PDGF-BB,HGF,G-CSF)但不发芽诱导剂(VEGF165)。使用RNA测序和基因本体测绘的转录组分析在Cs上调的蛋白质上的蛋白质,其称为胶原蛋白结合和GT成熟以及已知的脂肪酸代谢酶是血管发芽的负调节剂。同时,下调转录物被激活毛细管生长的因素富集,表明在MSC片中,旁静脉活性可能朝向基质重塑和血管系统成熟,但不激活血管发芽。我们提出了一种推定的剖腹症触发机制,可能会对GT血管化和重塑产生影响。我们的研究结果表明,在表中,MSC可以改变其功能状态和溶解的可溶性因子,这些因子影响组织修复并诱导更有效的皮肤愈合倾向于再生和减少瘢痕。

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