Xaymardan Munira, Gibbins John R, Zoellner Hans
Cellular and Molecular Pathology Research Unit, Department of Oral Medicine and Oral Pathology, University of Sydney, Westmead Hospital Dental Clinical School, Westmead Hospital, NSW, Australia.
Anat Rec. 2002 May 1;267(1):28-36. doi: 10.1002/ar.10072.
In mammals, wound healing is thought to result in the formation of scar tissue, with the exception of bony healing after fractures. Here we describe a previously unknown pattern of wound healing in which adipose rather than scar tissue is formed. Adipogenesis is normally confined to the embryo, although there are several experimental models for adipogenesis with highly specific dietary, cytokine, matrix, sex, or age requirements. The adipogenic healing described in this work provides a simple and reproducible experimental mouse model for adipogenesis without these limitations. Mice received intramuscular implants of nylon mesh material. Fibrinous material impregnated implants and within 4 weeks was replaced with highly vascular granulation tissue, typical of wound healing. Also consistent with wound healing was a reduction in vascularity of the newly formed tissue over time (P < 0.05). Lipoblasts were prevalent in granulation tissue, reaching a maximum in week 2 (P < 0.001) but falling to very low levels by week 9. These cells matured to adipocytes, with intermediate forms being seen. The identity of lipoblasts and adipocytes was confirmed by Oil Red O staining and electron microscopy. Control experiments confirmed that adipogenesis was independent of the materials used as well as of the sex and age of the animals. Rather, adipogenesis appeared to be due to replacement of fibrinous material in a space created within muscle. It is possible that adipogenic healing represents an adaptation for limiting the formation of restrictive scar tissues within muscle, and that this is the basis for the formation of traumatic lipomas in humans. Also, muscle tissue is replaced by adipose cells, seemingly derived from pluripotential satellite cells, in several degenerative muscle conditions, suggesting a role for adipogenic healing in these conditions.
在哺乳动物中,除骨折后的骨愈合外,伤口愈合通常会形成瘢痕组织。在此,我们描述了一种此前未知的伤口愈合模式,即形成的是脂肪组织而非瘢痕组织。脂肪生成通常局限于胚胎期,不过有几种脂肪生成的实验模型,它们对饮食、细胞因子、基质、性别或年龄有高度特定的要求。本研究中所描述的脂肪生成性愈合提供了一种简单且可重复的实验小鼠模型,用于脂肪生成,且不存在这些限制。给小鼠植入肌肉内尼龙网材料。植入物被纤维蛋白物质浸润,4周内被典型伤口愈合的高度血管化肉芽组织所取代。新形成组织的血管随着时间推移而减少(P<0.05),这也与伤口愈合情况一致。成脂细胞在肉芽组织中普遍存在,在第2周达到峰值(P<0.001),但到第9周时降至极低水平。这些细胞成熟为脂肪细胞,可见中间形态。通过油红O染色和电子显微镜证实了成脂细胞和脂肪细胞的特性。对照实验证实,脂肪生成与所用材料以及动物的性别和年龄无关。相反,脂肪生成似乎是由于肌肉内形成的空间中纤维蛋白物质被替代所致。脂肪生成性愈合可能是一种限制肌肉内形成限制性瘢痕组织的适应性反应,这也是人类创伤性脂肪瘤形成的基础。此外,在几种退行性肌肉疾病中,肌肉组织被脂肪细胞替代,这些脂肪细胞似乎来源于多能卫星细胞,这表明脂肪生成性愈合在这些疾病中发挥了作用。