Department of Otorhinolaryngology-Head and Neck Surgery, Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Republic of Korea.
Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, Busan, Republic of Korea.
Cell Death Dis. 2018 Feb 7;9(2):183. doi: 10.1038/s41419-017-0248-4.
As tissue engineering and regenerative medicine have evolved recently, stem cell therapy has been investigated in the field of impaired wound healing. Several studies have reported that mesenchymal stem cells derived from various tissues including bone marrow and adipose tissue can exert the regenerative efficacy in the wound healing. Previously, we have demonstrated the isolation and characterization of tonsil-derived mesenchymal stem cells (TMSCs) with excellent proliferative property. In the present study, we aimed to evaluate the regenerative efficacy of TMSCs in the wound healing process. Two distinct cutaneous surgical defects were generated in the dorsum of mice. Each wound was treated with TMSCs or phosphate-buffered saline (PBS), respectively. After sacrifice, the skin and subcutaneous tissues around the surgical defect were harvested and assessed for inflammation, re-epithelialization, dermal regeneration, and granulation tissue formation. The administration of TMSCs into wound beds significantly promoted the repair of surgical defects in mice. Especially, TMSCs efficiently contributed to the attenuation of excessive inflammation in the surgical lesion, as well as the augmentation of epidermal and dermal regeneration. To elucidate the underlying mechanisms, TMSCs were analyzed for their potency in immunomodulatory ability on immune cells, stimulatory effect on the proliferation of keratinocytes, and fibroblasts, as well as the regulation of fibroblast differentiation. TMSCs inhibited the non-specific or T-cell-specific proliferation of peripheral blood mononuclear cells, as well as the M1 polarization of macrophage-like cells. Moreover, TMSCs augmented the proliferation of skin-constituting fibroblasts and keratinocytes while they suppressed the differentiation of fibroblasts into myofibroblasts. Taken together, our findings demonstrate the regenerative potential of TMSCs in wound healing process through the regulation on inflammation, proliferation, and remodeling of various skin cells, implying that TMSCs can be a promising alternative for wound repair.
随着组织工程和再生医学的发展，干细胞疗法在受损伤口愈合领域得到了研究。多项研究报告称，源自骨髓和脂肪组织等多种组织的间充质干细胞可在伤口愈合中发挥再生功效。此前，我们已经证明了扁桃体来源的间充质干细胞（TMSC）具有出色的增殖特性，可以从扁桃体中分离和鉴定。在本研究中，我们旨在评估 TMSC 在伤口愈合过程中的再生功效。在小鼠背部制造了两个不同的皮肤外科缺损。每个伤口分别用 TMSC 或磷酸盐缓冲盐水（PBS）处理。处死后，采集手术缺损周围的皮肤和皮下组织，评估炎症、再上皮化、真皮再生和肉芽组织形成。TMSC 给药到伤口床显著促进了小鼠外科缺损的修复。特别是，TMSC 有效地有助于减轻手术病变中的过度炎症，以及增加表皮和真皮再生。为了阐明潜在机制，我们分析了 TMSC 对免疫细胞的免疫调节能力、对角质形成细胞和成纤维细胞增殖的刺激作用，以及对成纤维细胞分化的调节作用。TMSC 抑制外周血单核细胞的非特异性或 T 细胞特异性增殖，以及巨噬细胞样细胞的 M1 极化。此外，TMSC 增强了皮肤构成性成纤维细胞和角质形成细胞的增殖，同时抑制了成纤维细胞向肌成纤维细胞的分化。综上所述，我们的研究结果表明 TMSC 通过调节各种皮肤细胞的炎症、增殖和重塑，具有伤口愈合的再生潜力，表明 TMSC 可以成为伤口修复的一种有前途的替代方法。
