Human Periodontal Ligament- and Gingiva-derived Mesenchymal Stem Cells Promote Nerve Regeneration When Encapsulated in Alginate/Hyaluronic Acid 3D Scaffold.
Human Periodontal Ligament- and Gingiva-derived Mesenchymal Stem Cells Promote Nerve Regeneration When Encapsulated in Alginate/Hyaluronic Acid 3D Scaffold.
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DOI：
10.1002/adhm.201700670
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发表时间：
2017-12
影响因子：
10
通讯作者：
Moshaverinia A
中科院分区：
文献类型：
--
作者：
Ansari S;Diniz IM;Chen C;Sarrion P;Tamayol A;Wu BM;Moshaverinia A
受损神经的修复或再生在重建外科和再生医学中仍是一项具有挑战性的临床任务。在这里，我们通过裸鼠皮下移植模型，证明了从成人牙周和牙龈组织中分离的牙周韧带干细胞(PDLSCs)和牙周间充质干细胞(GMSCs)在体外和体内都具有神经表型。将PDLSCs和GMSCs包裹在以海藻酸盐和透明质酸水凝胶为基础的三维支架中，该支架能够持续释放人神经生长因子(NGF)。我们证明，水凝胶的弹性影响支架内包裹的MSCs的增殖和分化。此外，我们还观察到PDLSCs和GMSCs的βⅢ-微管蛋白染色呈阳性，而与神经源性分化相关的基因(βIII-微管蛋白和胶质原纤维酸性蛋白)在定量聚合酶链式反应中呈高表达。Western印迹分析表明基质的弹性和NGF的存在在包裹的MSCs的神经源性分化中具有重要意义。在体内，神经源性特定蛋白标记物的免疫荧光染色证实了移植水凝胶内密集的阳性染色结构。据我们所知，这项研究首次证明了PDLSCs和GMSCs作为有希望的神经再生细胞治疗候选细胞的应用。以海藻酸盐和透明质酸水凝胶为基质，制备了弹性优化的三维水凝胶给药系统。将牙周膜干细胞(PDLSCs)和牙周间充质干细胞(GMSCs)包裹在工程支架中，研究表明包裹的MSCs向神经源性组织的增殖和分化受基质弹性和合适的信号分子的存在的调节。结果表明，包裹在3D可注射细胞输送支架中的MSCs有望成为神经组织工程细胞治疗的候选材料。
Repair or regeneration of damaged nerves is still a challenging clinical task in reconstructive surgeries and regenerative medicine. Here, we demonstrate that periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) isolated from adult human periodontal and gingival tissues assume neuronal phenotype in vitro and in vivo via a subcutaneous transplantation model in nude mice. PDLSCs and GMSCs were encapsulated in a three-dimensional scaffold based on alginate and hyaluronic acid hydrogels capable of sustained release of human nerve growth factor (NGF). We demonstrate that, the elasticity of the hydrogels affected the proliferation and differentiation of encapsulated MSCs within scaffolds. Moreover, we observed that PDLSCs and GMSCs were stained positive for βIII-tubulin, while exhibiting high levels of gene expression related to neurogenic differentiation (βIII-tubulin and GFAP) via qPCR. Western blot analysis showed the importance of the elasticity of the matrix and the presence of NGF in the neurogenic differentiation of encapsulated MSCs. In vivo, immunofluorescence staining for neurogenic specific protein markers confirmed islands of dense positively stained structures inside transplanted hydrogels. To our knowledge, this study is the first demonstration of the application of PDLSCs and GMSCs as promising cell therapy candidates for nerve regeneration. A 3D hydrogel delivery system is fabricated based on alginate and hyaluronic acid hydrogels, with optimized elasticity. Periodontal Ligament Stem Cells (PDLSCs) and Gingival Mesenchymal Stem Cells (GMSCs) are encapsulated in the engineered scaffold and it is demonstrated that proliferation and differentiation of encapsulated MSCs toward neurogenic tissues is regulated by matrix elasticity and the presence of a suitable signaling molecules. It is shown that these MSCs encapsulated in a 3D injectable cell delivery scaffold might be promising candidates for cellular-based treatment for nerve tissue engineering.
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影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
通讯作者：
Mooney DJ
影响因子：
6
作者：
Cantu, David Antonio;Hematti, Peiman;Kao, Weiyuan John
通讯作者：
Kao, Weiyuan John
影响因子：
4.2
作者：
Kiraly, Marianna;Porcsalmy, Balazs;Varga, Gabor
通讯作者：
Varga, Gabor
影响因子：
82.9
作者：
Bi, Yanming;Ehirchiou, Driss;Young, Marian F.
通讯作者：
Young, Marian F.
影响因子：
14
作者：
Kutty, Jaishankar K.;Cho, Eunhee;Webb, Ken
通讯作者：
Webb, Ken