3D bioprinted extracellular matrix mimics facilitate directed differentiation of epithelial progenitors for sweat gland regeneration
3D bioprinted extracellular matrix mimics facilitate directed differentiation of epithelial progenitors for sweat gland regeneration
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3D生物打印细胞外基质模拟物促进上皮祖细胞定向分化以促进汗腺再生
DOI：
10.1016/j.actbio.2015.12.039
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发表时间：
2016-03-01
影响因子：
9.7
通讯作者：
Fu, Xiaobing
中科院分区：
文献类型：
--
作者：
Huang, Sha;Yao, Bin;Fu, Xiaobing
在哺乳动物中，汗腺具有重要的体温调节功能。像其他皮肤附属物一样，它们起源于表皮祖细胞。然而，它们对损伤的再生潜力很低，并且成年表皮祖细胞是否可以分化为汗腺细胞谱系仍然在很大程度上未被探索。我们使用生物打印技术来创建具有基于明胶和海藻酸钠的复合水凝胶的功能性体外细胞负载3D细胞外基质模拟物（3D-ECM），因为其与ECM组分的化学和结构相似。为了实现特异性细胞分化，将小鼠足底真皮和表皮生长因子同步掺入3D-ECM模拟物中，以产生从小鼠获得的表皮祖细胞的诱导小生境。生物3D构建体可以保持细胞活力，从而促进细胞铺展和基质形成。通过免疫荧光和关键细胞表面标志物的基因表达测定的体外数据表明，生物打印的3D-ECM可以有效地为表皮祖细胞创造限制性生态位，确保单侧分化为汗腺细胞。此外，将生物打印的3D ECM直接递送到小鼠烧伤的爪子中导致汗腺的功能恢复。这项研究代表了使用3D生物打印增强表皮谱系特异性分化的合理设计，并可能在再生汗腺方面具有临床和翻译意义。重要性声明损伤后的汗腺再生具有临床重要性，但由于再生潜力低且缺乏明确的生态位，因此在很大程度上仍未解决。一些研究已经表明，通过胚胎成分进行基于基因的干预或基于细胞的诱导可以实现汗腺再生，但将其转化为临床具有挑战性。这项工作的新奇和重要性在于，我们设计了一种3D生物打印的细胞外基质，为增强表皮谱系的特异性分化提供空间诱导线索，以再生汗腺，这对于治疗深度烧伤或其他伤口至关重要。我们的研究令人鼓舞，因为我们设计的3D生物打印结构在维持高细胞增殖方面优于其他细胞递送技术;另一个有趣的发现是，成人组织成分保留了胚胎组织的腺体谱系诱导能力，这可以促进翻译。(C)2015 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Sweat glands perform a vital thermoregulatory function in mammals. Like other skin appendages, they originate from epidermal progenitors. However, they have low regenerative potential in response to injury, and whether adult epidermal progenitors could be specified to differentiate to a sweat gland cell lineage remains largely unexplored. We used bioprinting technology to create a functional in vitro cell laden 3D extracellular matrix mimics (3D-ECM) with composite hydrogels based on gelatin and sodium alginate because of chemical and structural similarity to ECM components. To achieve specific cell differentiation, mouse plantar dermis and epidermal growth factor were synchronously incorporated into the 3D-ECM mimics to create an inductive niche for epidermal progenitor cells obtained from mice. The biological 3D construct could maintain cell viability, thereby facilitating cell spreading and matrix formation. In vitro data by immunofluorescence and gene expression assay of key cell-surface markers demonstrated that the bioprinted 3D-ECM could effectively create a restrictive niche for epidermal progenitors that ensures unilateral differentiation into sweat gland cells. Furthermore, direct delivery of bioprinted 3D ECM into burned paws of mice resulted in functional restoration of sweat glands. This study represents the rational design to enhance the specific differentiation of epidermal lineages using 3D bioprinting and may have clinical and translational implications in regenerating sweat glands.Statement of SignificanceSweat gland regeneration after injury is of clinical importance but remains largely unsolved because of low regenerative potential and lack of a definite niche. Some studies have shown sweat gland regeneration with gene-based interventions or cell-based induction via embryonic components, but translation to clinic is challenging. The novelty and significance of the work lies in the fact that we design a 3D bioprinted extracellular matrix that provides the spatial inductive cues for enhancing specific differentiation of epidermal lineages to regenerate sweat glands, which is critical for treating deep burns or other wounds. Our studies are encouraging given the overwhelming advantages of our designed 3D bioprinting construct over other cell delivery technology in maintaining high cell proliferation; another interesting finding is that adult tissue components retain a gland lineage-inductive power as embryonic tissue, which can facilitate translation. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.