The Skin-to-Mucosa Ratio Defines the Osteogenic Potential of Lip Fibroblasts.

L Parisi, F Mansour, S Rihs, I Schnyder, G C La Scala, C Katsaros, M Degen
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Abstract

Fibroblasts isolated from discarded lip tissue obtained during cheiloplasty in patients with cleft lip/palate (CLP) show promising osteogenic potential and may be an appealing cell source for autologous bone regeneration. As the lip is a mucocutaneous junction, explant cultures from unseparated lip biopsies produce mesenchymal outgrowths composed of skin- and mucosa-derived fibroblasts. The proportions of the 2 fibroblast populations, however, differ among CLP patients and depend on the morphology of the excised sample, which is unique for each donor. Understanding the osteogenic activities of CLP fibroblast populations with varying skin-to-mucosa ratios is critical for their therapeutic application. We isolated CLP fibroblasts from 10 unseparated lip biopsies and comprehensively evaluated them for their bone differentiation capacities in vitro, demonstrating heterogeneous osteogenic potentials. Because there are no markers that can distinguish skin from mucosa fibroblasts, we used the respective and matching CLP keratinocytes to ascertain the skin-to-mucosa ratio of the 10 specimens. Thus, we found that CLP fibroblasts isolated from biopsies with high skin-to-mucosa ratios had a much higher osteogenic capacity than those derived from biopsies with low skin-to-mucosa ratios. To validate and solidify these findings, we carefully separated skin and mucosa tissues during corrective lip surgery to isolate pure skin and mucosa CLP lip fibroblasts. Indeed, skin had a higher osteogenic potential than their mucosal counterparts did. Furthermore, we discovered that the high osteogenic activity in skin was limited to specific subpopulations of yet unknown identities. Our findings indicate that skin fibroblasts perform better than their mucosal counterparts do, even though both types of fibroblasts can differentiate into bone-forming cells.

皮肤与粘膜的比例决定了唇部成纤维细胞的成骨潜能。
从唇裂/腭裂(CLP)患者唇部成形术中获得的废弃唇组织中分离的成纤维细胞显示出良好的成骨潜力,可能是一种有吸引力的自体骨再生细胞来源。由于唇部是粘膜与皮肤的交界处,从未分离的唇活检组织中提取的外植体培养物产生由皮肤和粘膜来源的成纤维细胞组成的间充质产物。然而,两种成纤维细胞群的比例在CLP患者中有所不同,并且取决于切除样本的形态,这对于每个供者来说都是独特的。了解具有不同皮肤-粘膜比例的CLP成纤维细胞群体的成骨活性对其治疗应用至关重要。我们从10个未分离的嘴唇活检中分离出CLP成纤维细胞,并对其体外骨分化能力进行了全面评估,显示出异质成骨潜力。由于没有标记物可以区分皮肤和粘膜成纤维细胞,我们使用各自的和匹配的CLP角质形成细胞来确定10个标本的皮肤-粘膜比例。因此,我们发现从皮肤与粘膜比例高的活检中分离的CLP成纤维细胞比从皮肤与粘膜比例低的活检中分离的CLP成纤维细胞具有更高的成骨能力。为了验证和巩固这些发现,我们在唇矫正手术中仔细分离皮肤和粘膜组织,分离纯皮肤和粘膜CLP唇成纤维细胞。事实上,皮肤比粘膜具有更高的成骨潜力。此外,我们发现皮肤中的高成骨活性仅限于尚未确定身份的特定亚群。我们的研究结果表明,皮肤成纤维细胞比粘膜成纤维细胞表现更好,尽管两种类型的成纤维细胞都可以分化成骨形成细胞。
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