Molecular weight and concentration of heparin in hyaluronic acid-based matrices modulates growth factor retention kinetics and stem cell fate.
Molecular weight and concentration of heparin in hyaluronic acid-based matrices modulates growth factor retention kinetics and stem cell fate.
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DOI：
10.1016/j.jconrel.2015.04.034
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发表时间：
2015-07-10
期刊：
影响因子：
--
通讯作者：
Healy KE
中科院分区：
文献类型：
--
作者：
Jha AK;Mathur A;Svedlund FL;Ye J;Yeghiazarians Y;Healy KE
生长因子是调节和诱导各种干细胞功能的关键。为了研究生长因子传递动力学和呈现对干细胞命运的影响，我们开发了一系列含肝素透明质酸（HyA）的水凝胶，这些水凝胶具有不同程度的生长因子亲和力和保留率。为了表征该系统，我们研究了肝素分子量、分离和相对浓度对tgf - β1的装载效率和保留动力学的影响。在相同浓度下，高分子量的肝素装载和保留了最多的tgf - β1，并且具有最慢的释放动力学，这主要是因为与低分子量或未分离的肝素相比，高分子量的肝素与tgf - β1的亲和力更高。随后，我们测试了TGFβ1的作用，从各种含肝素的基质中提取，将Sca-1+/CD45−心脏祖细胞（CPCs）分化为内皮细胞，并在体外形成血管样网络。高分子量的肝素- HyA水凝胶刺激了内皮细胞向内皮细胞的更强分化，内皮细胞在水凝胶内形成血管样网络。这一观察结果归因于高分子量肝素HyA水凝胶在基质内隔离内源性合成血管生成因子的能力。这些结果证明了肝素的分子量、分离和浓度对肝素结合生长因子的表达及其对干细胞分化和谱系规范的影响的重要性。
Growth factors are critical for regulating and inducing various stem cell functions. To study the effects of growth factor delivery kinetics and presentation on stem cell fate, we developed a series of heparin-containing hyaluronic acid (HyA)-based hydrogels with various degrees of growth factor affinity and retention. To characterize this system, we investigated the effect of heparin molecular weight, fractionation, and relative concentration on the loading efficiency and retention kinetics of TGFβ1 as a model growth factor. At equal concentrations, high MW heparin both loaded and retained the greatest amount of TGFβ1, and had the slowest release kinetics, primarily due to the higher affinity with TGFβ1 compared to low MW or unfractionated heparin. Subsequently, we tested the effect of TGFβ1, presented from various heparin-containing matrices, to differentiate a versatile population of Sca-1+/CD45− cardiac progenitor cells (CPCs) into endothelial cells and form vascular-like networks in vitro. High MW heparin HyA hydrogels stimulated more robust differentiation of CPCs into endothelial cells, which formed vascular-like networks within the hydrogel. This observation was attributed to the ability of high MW heparin HyA hydrogels to sequester endogenously synthesized angiogenic factors within the matrix. These results demonstrate the importance of molecular weight, fractionation, and concentration of heparin on presentation of heparin-binding growth factors and their effect on stem cell differentiation and lineage specification.
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