Laboratory for Tissue Engineering and Regenerative Medicine, Tel Aviv 69978, Israel; Laboratory for Precision NanoMedicine, School for Molecular Cell Biology and Biotechnology, Tel Aviv 69978, Israel.
Laboratory for Precision NanoMedicine, School for Molecular Cell Biology and Biotechnology, Tel Aviv 69978, Israel; Department of Materials Science and Engineering, Tel Aviv 69978, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel.
J Control Release. 2017 Jul 10;257:84-90. doi: 10.1016/j.jconrel.2016.09.021. Epub 2016 Sep 23.
The success of hematopoietic stem cells (HSCs) transplantation is limited due to the low number of HSCs received from donors. In vivo, HSCs reside within a specialized niche inside the 3D porous spongy bone. The natural environment in the niche is composed of structural proteins, glycosaminoglycans (GAGs) and soluble factors that control cells fate. However, the designed scaffolds for in vitro culture do not fairly recapitulate this microenvironment and cannot efficiently control HSCs fate. Here we report on the development of new omental ECM-based 3D macroporous sponges for hematopoietic cell culture. The scaffolds' structure, porosity and stability were characterized and optimized. Analysis of the biochemical content revealed that they were composed of collagens and GAGs, including sulfated GAGs. This morphology and composition enabled growth factors interaction with the sulfated GAGs, as indicated by the high loading capacity and release profile of three different hematopoietic niche factors. Finally, the ability of the ECM-based scaffolds to efficiently support the growth of hematopoietic cells by releasing stem cell factor (SCF) was demonstrated.
造血干细胞 (HSCs) 移植的成功受到供体来源 HSCs 数量少的限制。在体内，HSCs 存在于 3D 多孔海绵骨内的一个专门龛位中。龛位中的自然环境由结构蛋白、糖胺聚糖 (GAG) 和可溶性因子组成，它们控制着细胞的命运。然而，用于体外培养的设计支架并不能完全再现这种微环境，也不能有效地控制 HSCs 的命运。在这里，我们报告了用于造血细胞培养的新型网膜细胞外基质 (ECM) 基 3D 大孔海绵的开发。对支架的结构、孔隙率和稳定性进行了表征和优化。生化成分分析表明，它们由胶原蛋白和 GAG 组成，包括硫酸化 GAG。这种形态和组成使生长因子能够与硫酸化 GAG 相互作用，这可以通过三种不同造血龛位因子的高负载能力和释放曲线来证明。最后，通过释放干细胞因子 (SCF)，证明了 ECM 支架能够有效地支持造血细胞的生长。
