Allogeneic fibroblasts in dermal substitutes induce inflammation and scar formation

Allogeneic fibroblasts in dermal substitutes induce inflammation and scar formation
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DOI:
10.1046/j.1524-475x.2002.10901.x
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发表时间:
2002-05-01
影响因子:
2.9
通讯作者:
Middelkoop, E
Middelkoop, E
中科院分区:
医学3区
文献类型:
--
作者:
Lamme, EN;Van Leeuwen, RTJ;Middelkoop, E

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在本研究中,我们在猪创伤模型中比较了自体和异体成纤维细胞在真皮替代物中的使用,异体成纤维细胞群体来自雌性和雄性猪(allo-1,-2和-3),以及对照,自体成纤维细胞,来自雌性移植受体猪(对照)。用混合淋巴细胞反应检测供体猪与受体猪的组织相容性。在两只猪中,全层创面用成纤维细胞种植的真皮替代物(每只动物5只)处理,并立即用网状自体裂皮片移植。6周后,用平面测量法测量创面收缩,并对瘢痕形成情况进行评分。在第2A和第6周取材,评估炎症反应、肌成纤维细胞和瘢痕形成,两个受体猪的混合淋巴细胞反应对allo-3供体猪外周血单个核细胞的反应最高,allo-1和allo-2反应很低或阴性。在所有“同种异体”创面中,随着时间的推移,随着时间的推移,更多的炎细胞伴随着由淋巴细胞和肉芽肿细胞组成的炎性灶出现。4周后,对照组创面中肌成纤维细胞消失,而“同种异体”创面中,肌成纤维细胞与炎症灶共存。“同种异体”伤口的最终疤痕组织显示肉芽区域有细小、未成熟的胶原束。相比之下,对照伤口显示出一种真皮组织,与正常皮肤一样,成熟的胶原束随机排列。与对照伤口相比,用allo-3成纤维细胞处理的两种猪的伤口显示出明显的疤痕形成和伤口收缩。总之,为了以最小的疤痕形成最佳地恢复真皮功能,含有自体成纤维细胞的皮肤替代物比含有同种异体成纤维细胞的皮肤替代物更受欢迎,
In the present study, we compared the use of autologous versus allogeneic fibroblasts in dermal skin substitutes in a porcine wound model, The allogeneic fibroblast populations were isolated from female and a male pig (allo-1, - 2 and - 3) and the controls, autologous fibroblasts, from female graft-recipient pigs (control). The histocompatibility of the three donor pigs with the recipient pigs was determined with a mixed lymphocyte reaction. In two pigs, full-thickness wounds were treated with the fibroblast-seeded dermal substitutes (n = 5 per animal) and immediately overgrafted with meshed split-skin autografts. After 6 weeks, wound contraction was measured by planimetry and scar formation was scored. At 2A and 6 weeks biopsies were taken and evaluated for the presence of inflammatory reactions, myofibroblasts, and scar formation, The mixed lymphocyte reaction of both recipient pigs showed the highest responses on peripheral blood mononuclear cells of the allo-3 donor pig, and was low or negative for allo-1 and allo-2, In all ''allogeneic" wounds, more inflammatory cells were observed over time along with inflammatory foci consisting of a mix of lymphocytes and granulomatous cells. After 4 weeks, myofibroblasts were absent in the control wounds, whereas in "allogeneic" wounds, myofibroblasts colocalized with inflammation foci. The final scar tissue of the "allogeneic" wounds showed granulating areas with thin, immature collagen bundles. In contrast, the control wounds showed a dermal tissue with mature collagen bundles organized randomly like in normal skin. The wounds treated with allo-3 fibroblasts showed in both pigs a significant increase in scar formation and wound contraction when compared with control wounds. In conclusion, for optimal restoration of dermal skin function with minimal scar formation, skin substitutes containing autologous fibroblasts are preferred over skin substitutes with allogeneic fibroblasts,