Fast-Degradable Microbeads Encapsulating Human Umbilical Cord Stem Cells in Alginate for Muscle Tissue Engineering
Fast-Degradable Microbeads Encapsulating Human Umbilical Cord Stem Cells in Alginate for Muscle Tissue Engineering
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DOI：
10.1089/ten.tea.2011.0658
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发表时间：
2012-11-01
影响因子：
4.1
通讯作者：
Trotman, Carroll Ann
中科院分区：
文献类型：
--
作者：
Liu, Jun;Zhou, Hongzhi;Trotman, Carroll Ann
人脐带间充质干细胞（hUCMSCs）是取之不尽的，可以在没有侵入性手术的情况下获得。迄今为止，还没有关于将hUCMSCs接种于三维支架中用于肌肉组织工程的报道。本研究的目的是（1）研究hUCMSC在肌肉工程支架中的接种和（2）开发一种由hUCMSC包封和水凝胶基质内的快速降解微珠组成的新型构建体。基本原理是水凝胶基质将保持缺损体积，而微珠将降解以释放细胞并同时在基质中产生大孔。将hUCMSC包封在藻酸盐-纤维蛋白微珠中，所述微珠包装在Arg-Gly-Asp（RGD）修饰的藻酸盐基质（AM）中。该构建体被称为hUCMSC-微珠-AM。对照由在AM中的常规细胞包封而没有微珠（称为hUCMSC-AM）组成。在hUCMSC-AM构建体中，hUCMSC在1-14天时显示为圆点，没有铺展。相比之下，hUCMSC-微珠-AM构建体中的细胞具有健康的铺展和伸长的形态。微珠在第8天成功降解并释放细胞。hUCMSC-微珠-AM的肌原性表达是hUCMSC-AM的三倍以上（p < 0.05）。hUCMSC-微珠-AM的肌原性标志物的免疫荧光比hUCMSC-AM强得多。在14天时，hUCMSC-微珠-AM的肌肉肌酸激酶是hUCMSC-AM的两倍（p < 0.05）。总之，研究了将hUCMSC包封在水凝胶基质内的新型快速降解微珠中用于肌肉工程。与通常的将细胞接种在水凝胶基质中的方法相比，hUCMSC-微珠-AM构建体大大提高了细胞活力和成肌分化，因此，有希望增强肌肉再生。
Human umbilical cord mesenchymal stem cells (hUCMSCs) are inexhaustible and can be obtained without an invasive surgery. To date, there has been no report on seeding hUCMSCs in three-dimensional scaffolds for muscle tissue engineering. The objectives of this study were to (1) investigate hUCMSC seeding in a scaffold for muscle engineering and (2) develop a novel construct consisting of hUCMSC-encapsulating and fast-degradable microbeads inside a hydrogel matrix. The rationale was that the hydrogel matrix would maintain the defect volume, while the microbeads would degrade to release the cells and concomitantly create macropores in the matrix. hUCMSCs were encapsulated in alginate-fibrin microbeads, which were packed in an Arg-Gly-Asp (RGD)-modified alginate matrix (AM). This construct is referred to as hUCMSC-microbead-AM. The control consisted of the usual cell encapsulation in AM without microbeads (referred to as hUCMSC-AM). In the hUCMSC-AM construct, the hUCMSCs showed as round dots with no spreading at 1-14 days. In contrast, cells in the hUCMSC-microbead-AM construct had a healthy spreading and elongated morphology. The microbeads successfully degraded and released the cells at 8 days. Myogenic expressions for hUCMSC-microbead-AM were more than threefold those of hUCMSC-AM (p < 0.05). Immunofluorescence for myogenic markers was much stronger for hUCMSC-microbead-AM than hUCMSC-AM. Muscle creatine kinase of hUCMSC-microbead-AM at 14 days was twofold that of hUCMSC-AM (p < 0.05). In conclusion, hUCMSC encapsulation in novel fast-degradable microbeads inside a hydrogel matrix was investigated for muscle engineering. Compared to the usual method of seeding cells in a hydrogel matrix, hUCMSC-microbead-AM construct had greatly improved cell viability and myogenic differentiation, and hence, is promising to enhance muscle regeneration.