Zhang Xue, Schipper Jan Aart M, Schepers Rutger H, Jansma Johan, Spijkervet Fred K L, Harmsen Martin C
Department of Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Biomolecules. 2024 Nov 23;14(12):1493. doi: 10.3390/biom14121493.
To accelerate cutaneous wound healing and prevent scarring, regenerative approaches such as injecting a mechanically derived tissue stromal vascular fraction (tSVF) are currently under clinical and laboratory investigations. The aim of our study was to investigate a platform to assess the interaction between skin-derived extracellular matrix (ECM) hydrogels and tSVF and their effects on their microenvironment in the first ten days of culture. A tSVF mixed with ECM hydrogel was cultured for ten days. After 0, 3, 5, and 10 days of culture viability, histology, immunohistochemistry, gene expression, and collagen alignment and organization were assessed. The viability analysis showed that tSVF remained viable during 10 days of culture and seemed to remain within their constitutive ECM. The fiber analysis demonstrated that collagen alignment and organization were not altered. No outgrowth of capillaries was observed in (immuno)histochemical staining. The gene expression analysis revealed that paracrine factors and did not change and yet were constitutively expressed. Pro-inflammatory factors and were downregulated. Matrix remodeling gene was upregulated from day three on, while was upregulated at day three and ten. Interestingly, was downregulated at day five compared to day three while was downregulated after day zero. Skin-derived ECM hydrogels appear to be a versatile platform for investigating the function of a mechanically isolated adipose tissue stromal vascular fraction. In vitro tSVF remained viable for 10 days and sustained the expression of pro-regenerative factors, but is in need of additional triggers to induce vascularization or show signs of remodeling of the surrounding ECM. In the future, ECM-encapsulated tSVF may show promise for clinical administration to improve wound healing.
为了加速皮肤伤口愈合并防止瘢痕形成，目前正在进行临床和实验室研究一些再生方法，如注射机械分离得到的组织基质血管成分（tSVF）。我们研究的目的是探究一个平台，以评估皮肤来源的细胞外基质（ECM）水凝胶与tSVF之间的相互作用及其在培养的前十天对其微环境的影响。将tSVF与ECM水凝胶混合培养十天。在培养0、3、5和10天后，评估细胞活力、组织学、免疫组织化学、基因表达以及胶原蛋白的排列和组织情况。活力分析表明，tSVF在培养的10天内保持活力，并且似乎保留在其组成性ECM内。纤维分析表明，胶原蛋白的排列和组织没有改变。在（免疫）组织化学染色中未观察到毛细血管的生长。基因表达分析显示，旁分泌因子未发生变化，但持续表达。促炎因子和被下调。基质重塑基因从第三天开始上调，而在第三天和第十天上调。有趣的是，与第三天相比，第五天下调，而在第零天后下调。皮肤来源的ECM水凝胶似乎是一个通用平台，用于研究机械分离的脂肪组织基质血管成分的功能。体外tSVF在10天内保持活力并维持促再生因子的表达，但需要额外的触发因素来诱导血管生成或显示周围ECM重塑的迹象。未来，ECM包裹的tSVF可能在临床应用中显示出改善伤口愈合的前景。
