Scaffolding kidney organoids on silk
Scaffolding kidney organoids on silk
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DOI：
10.1002/term.2830
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发表时间：
2019-05-01
影响因子：
3.3
通讯作者：
Oxburgh, Leif
中科院分区：
文献类型：
--
作者：
Gupta, Ashwani Kumar;Coburn, Jeannine M.;Oxburgh, Leif
终末期肾病影响美国数十万患者。治疗的选择是肾脏替代，但器官的可用性是有限的，需要替代组织来源。通过多能细胞重编程和定向分化，在实验室中产生新的肾组织已经成为可能。在目前的程序中，被称为类器官的细胞聚集体在浸没或空气-液体界面处生长。这些研究表明，肾组织可以从多能干细胞中产生，但他们也发现了局限性。首先是细胞聚集体的灌注是有限的，限制了它们可以生长的大小。第二个是聚集体缺乏方便植入和粘附或粘附到肾损伤区域所需的结构完整性。在这项研究中，我们评估了丝作为原代细胞和人类诱导多能干细胞肾脏组织生长和分化支持的能力。我们发现，细胞可以分化为上皮细胞的特点，发展中的肾脏在这种材料，这些结构保持移植后的包膜下的成人肾脏。血管投资可以通过添加血管内皮生长因子的支架，但移植物内的基质细胞的增殖提出了一个挑战，这将需要一些细胞生长和分化条件的重新调整。总之，我们发现丝可用于支持干细胞衍生的肾组织的生长。
End stage kidney disease affects hundreds of thousands of patients in the United States. The therapy of choice is kidney replacement, but availability of organs is limited, and alternative sources of tissue are needed. Generation of new kidney tissue in the laboratory has been made possible through pluripotent cell reprogramming and directed differentiation. In current procedures, aggregates of cells known as organoids are grown either submerged or at the air-liquid interface. These studies have demonstrated that kidney tissue can be generated from pluripotent stem cells, but they also identify limitations. The first is that perfusion of cell aggregates is limited, restricting the size to which they can be grown. The second is that aggregates lack the structural integrity required for convenient engraftment and suturing or adhesion to regions of kidney injury. In this study, we evaluated the capacity of silk to serve as a support for the growth and differentiation of kidney tissue from primary cells and from human induced pluripotent stem cells. We find that cells can differentiate to epithelia characteristic of the developing kidney on this material and that these structures are maintained following engraftment under the capsule of the adult kidney. Blood vessel investment can be promoted by the addition of vascular endothelial growth factor to the scaffold, but the proliferation of stromal cells within the graft presents a challenge, which will require some readjustment of cell growth and differentiation conditions. In summary, we find that silk can be used to support growth of stem cell derived kidney tissue.