Waasdorp Maaike, Vahav Irit, Nugteren-Boogaard Joline Paulina, Roffel Sanne, Gibbs Susan
Department of Molecular Cell Biology and Immunology, Amsterdam Institute for Infection and Immunity, Amsterdam UMCs Location VUmc, Amsterdam, the Netherlands.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Wound Repair Regen. 2025 May-Jun;33(3):e70047. doi: 10.1111/wrr.70047.
Wound healing is an essential and complex biological mechanism to repair barrier breaches in the human body, but it results in scar formation. The extent of scar formation is associated with the depth of injury. Stromal cells play a vital role in wound healing and scar formation, but the role of the subcutaneous tissue in human skin wound healing remains largely unknown. In order to dissect the role of dermal fibroblasts, adipose stromal cells, and adipocytes in superficial and deep skin wound healing, we created a human tissue-engineered skin model and assessed healing outcomes in vitro. Three different reconstructed skin models were created, with dermal fibroblasts, adipose stromal cells, or adipocytes in the wound bed underneath a standardised biopsy punch wound. The superficial skin wound model with only dermal fibroblasts in the wound bed was completely healed within 14 days. The engineered 'deep' wounds with adipocytes in the wound bed showed delayed wound closure with reduced Ki67 proliferating keratinocytes and reduced basement membrane collagen IV deposition. This was accompanied by increased wound contraction and α-SMA protein expression underneath the newly formed epidermis, indicative of early scar formation. The 'deep' wound model with adipose stromal cells but without adipocytes showed improved re-epithelialisation but still healed with increased α-SMA protein expression. Furthermore, decreased leptin was observed in the supernatant of the 'deep' wound model. The superficial and deep wound models presented here can be used to test future therapies to improve wound closure which will lead to improved scar formation.
伤口愈合是人体修复屏障破损的一种重要且复杂的生物学机制，但会导致瘢痕形成。瘢痕形成的程度与损伤深度相关。基质细胞在伤口愈合和瘢痕形成中起着至关重要的作用，但皮下组织在人类皮肤伤口愈合中的作用仍 largely unknown。为了剖析真皮成纤维细胞、脂肪基质细胞和脂肪细胞在浅表和深部皮肤伤口愈合中的作用，我们创建了一种人体组织工程皮肤模型，并在体外评估愈合结果。创建了三种不同的重建皮肤模型，在标准化活检打孔伤口下方的伤口床中分别含有真皮成纤维细胞、脂肪基质细胞或脂肪细胞。伤口床中仅含有真皮成纤维细胞的浅表皮肤伤口模型在 14 天内完全愈合。伤口床中含有脂肪细胞的工程化“深部”伤口显示伤口闭合延迟，Ki67 增殖角质形成细胞减少，基底膜胶原蛋白 IV 沉积减少。这伴随着伤口收缩增加以及新形成表皮下方α-SMA 蛋白表达增加，表明早期瘢痕形成。含有脂肪基质细胞但不含脂肪细胞的“深部”伤口模型显示上皮再形成有所改善，但愈合时α-SMA 蛋白表达仍增加。此外，在“深部”伤口模型的上清液中观察到瘦素减少。这里呈现的浅表和深部伤口模型可用于测试未来改善伤口闭合的疗法，这将有助于改善瘢痕形成。
