Centre for the Cellular Microenvironment, University of Glasgow, Glasgow, G12 8LT, UK.
Adv Healthc Mater. 2022 Oct;11(20):e2200964. doi: 10.1002/adhm.202200964. Epub 2022 Aug 18.
Living biointerfaces are a new class of biomaterials combining living cells and polymeric matrices that can act as biologically active and instructive materials that host and provide signals to surrounding cells. Here, living biomaterials based on Lactococcus lactis to control hematopoietic stem cells in 2D surfaces and 3D hydrogels are introduced. L. lactis is modified to express C-X-C motif chemokine ligand 12 (CXCL12), thrombopoietin (TPO), vascular cell adhesion protein 1 (VCAM1), and the 7th-10th type III domains of human plasma fibronectin (FN III ), in an attempt to mimic ex vivo the conditions of the human bone marrow. These results suggest that living biomaterials that incorporate bacteria expressing recombinant CXCL12, TPO, VCAM1, and FN in both 2D systems direct hematopoietic stem and progenitor cells (HSPCs)-bacteria interaction, and in 3D using hydrogels functionalized with full-length human plasma fibronectin allow for a notable expansion of the CD34 /CD38 /CD90 HSPC population compared to the initial population. These results provide a strong evidence based on data that suggest the possibility of using living materials based on genetically engineered bacteria for the ex-vivo expansion of HSPC with eventual practical clinical applications in HSPCs transplantation for hematological disorders.
活生物界面是一类新的生物材料，它将活细胞和聚合物基质结合在一起，可以作为具有生物活性和指导作用的材料，为周围细胞提供支持和信号。在这里，我们介绍了基于乳球菌（Lactococcus lactis）的活生物材料，用于控制 2D 表面和 3D 水凝胶中的造血干细胞。我们对乳球菌进行了修饰，使其表达 C-X-C 基序趋化因子配体 12（CXCL12）、血小板生成素（TPO）、血管细胞黏附蛋白 1（VCAM1）和人血浆纤维连接蛋白的第 7-10 型 III 结构域（FN III ），试图在体外模拟人类骨髓的条件。这些结果表明，在 2D 系统中表达重组 CXCL12、TPO、VCAM1 和 FN 的活生物材料可以引导造血干细胞和祖细胞（HSPCs）与细菌的相互作用，而在 3D 中使用全长人血浆纤维连接蛋白功能化的水凝胶与初始群体相比，可显著扩增 CD34/CD38/CD90 HSPC 群体。这些结果基于数据提供了强有力的证据，表明使用基于基因工程细菌的活材料进行 HSPC 的体外扩增具有实际的临床应用前景，可用于血液系统疾病的 HSPC 移植。
