Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells
Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells
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DOI：
10.5966/sctm.2013-0217
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发表时间：
2014-10-01
影响因子：
6
通讯作者：
Eugenia Balana, Maria
中科院分区：
文献类型：
--
作者：
Jose Leiros, Gustavo;Gabriela Kusinsky, Ana;Eugenia Balana, Maria
组织工程皮肤是治疗深部皮肤损伤的一种有效策略，可能有助于理解皮肤再生。通过研究组织工程皮肤的结构、干细胞的持久性、毛发再生和裸鼠移植物的吸收，评价了毛乳头细胞（DPC）作为与人毛囊干细胞（HFSC）的永久性复合皮肤的真皮成分的使用。将猪无细胞真皮基质与单独的HFSC和HFSC加人DPC或真皮成纤维细胞（DF）接种。在体外，DPC的存在下诱导一个更规则的和多层分层的表皮与更多的基底p63阳性细胞和内陷。含有DPC的构建体通过适当地分层分化的HFSC并发育良好有序的上皮细胞来更准确地模拟皮肤结构，所述上皮细胞有助于更紧密地再现人造人类皮肤。将这种先前在体外用HFSC和DF或DPC作为真皮组分再增殖的无细胞真皮基质移植到裸鼠中。DPC在复合替代物中的存在不仅有利于移植后早期的新生血管形成、良好的同化和重塑，而且还有助于新生血管网络的成熟，这可能会减少炎症过程，从而导致更好的愈合过程，具有更少的瘢痕形成和伤口收缩。有趣的是，只有含DPC的构建体显示出具有人源细胞的胚胎毛芽样结构、前体上皮细胞的存在和毛发分化标记物的表达。虽然是初步的，但这些发现已经证明了DPC的存在对于适当的皮肤修复的重要性。
Tissue-engineered skin represents a useful strategy for the treatment of deep skin injuries and might contribute to the understanding of skin regeneration. The use of dermal papilla cells (DPCs) as a dermal component in a permanent composite skin with human hair follicle stem cells (HFSCs) was evaluated by studying the tissue-engineered skin architecture, stem cell persistence, hair regeneration, and graft-take in nude mice. A porcine acellular dermal matrix was seeded with HFSCs alone and with HFSCs plus human DPCs or dermal fibroblasts (DFs). In vitro, the presence of DPCs induced a more regular and multilayered stratified epidermis with more basal p63-positive cells and invaginations. The DPC-containing constructs more accurately mimicked the skin architecture by properly stratifying the differentiating HFSCs and developing a well-ordered epithelia that contributed to more closely recapitulate an artificial human skin. This acellular dermal matrix previously repopulated in vitro with HFSCs and DFs or DPCs as the dermal component was grafted in nude mice. The presence of DPCs in the composite substitute not only favored early neovascularization, good assimilation and remodeling after grafting but also contributed to the neovascular network maturation, which might reduce the inflammation process, resulting in a better healing process, with less scarring and wound contraction. Interestingly, only DPC-containing constructs showed embryonic hair bud-like structures with cells of human origin, presence of precursor epithelial cells, and expression of a hair differentiation marker. Although preliminary, these findings have demonstrated the importance of the presence of DPCs for proper skin repair.