Jabbari Esmaiel, Sepahvandi Azadeh
Biomaterials and Tissue Engineering Laboratory, Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA.
Gels. 2022 Feb 27;8(3):148. doi: 10.3390/gels8030148.
Conventional microcarriers used for expansion of human mesenchymal stem cells (hMSCs) require detachment and separation of the cells from the carrier prior to use in clinical applications for regeneration of articular cartilage, and the carrier can cause undesirable phenotypic changes in the expanded cells. This work describes a novel approach to expand hMSCs on biomimetic carriers based on adult or fetal decellularized bovine articular cartilage that supports tissue regeneration without the need to detach the expanded cells from the carrier. In this approach, the fetal or adult bovine articular cartilage was minced, decellularized, freeze-dried, ground, and sieved to produce articular cartilage microgels (CMGs) in a specified size range. Next, the hMSCs were expanded on CMGs in a bioreactor in basal medium to generate hMSC-loaded CMG microgels (CMG-MSCs). Then, the CMG-MSCs were suspended in sodium alginate, injected in a mold, crosslinked with calcium chloride, and incubated in chondrogenic medium as an injectable cellular construct for regeneration of articular cartilage. The expression of chondrogenic markers and compressive moduli of the injectable CMG-MSCs/alginate hydrogels incubated in chondrogenic medium were higher compared to the hMSCs directly encapsulated in alginate hydrogels.
用于扩增人间充质干细胞（hMSCs）的传统微载体，在用于关节软骨再生的临床应用之前，需要将细胞从载体上分离下来，并且载体可能会在扩增的细胞中引起不良的表型变化。这项工作描述了一种基于成年或胎儿去细胞化牛关节软骨的仿生载体上扩增hMSCs的新方法，该载体支持组织再生，而无需将扩增的细胞从载体上分离下来。在这种方法中，将胎儿或成年牛关节软骨切碎、去细胞化、冻干、研磨并过筛，以产生特定尺寸范围内的关节软骨微凝胶（CMGs）。接下来，hMSCs在生物反应器中于基础培养基中在CMGs上扩增，以生成负载hMSC的CMG微凝胶（CMG-MSCs）。然后，将CMG-MSCs悬浮在海藻酸钠中，注入模具中，用氯化钙交联，并在软骨形成培养基中孵育，作为用于关节软骨再生的可注射细胞构建体。与直接封装在海藻酸盐水凝胶中的hMSCs相比，在软骨形成培养基中孵育的可注射CMG-MSCs/海藻酸盐水凝胶的软骨形成标志物表达和压缩模量更高。
