Enhanced survival and engraftment of transplanted stem cells using growth factor sequestering hydrogels.
Enhanced survival and engraftment of transplanted stem cells using growth factor sequestering hydrogels.
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DOI：
10.1016/j.biomaterials.2014.12.043
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发表时间：
2015-04
期刊：
影响因子：
14
通讯作者：
Healy, Kevin E.
中科院分区：
文献类型：
--
作者：
Jha, Amit K.;Tharp, Kevin M.;Ye, Jianqin;Santiago-Ortiz, Jorge L.;Jackson, Wesley M.;Stahl, Andreas;Schaffer, David V.;Yeghiazarians, Yerem;Healy, Kevin E.
关键词：
我们已经产生了用于基质辅助细胞移植（MACT）的基于透明质酸（HyA）的水凝胶的生物启发可调系统。使用这种材料，我们独立评估了基质参数，如粘附肽密度，机械性能和生长因子螯合能力，以设计一种环境，使供体细胞具有促进移植后宿主组织存活和植入的环境。使用Sca-1+/CD 45 −心脏祖细胞（CPC）的多功能群体，我们证明了在HyA水凝胶中添加肝素对于协调TGFβ1的呈递并通过内皮细胞分化和血管样管状网络形成支持CPC的营养功能是必要的。外源性TGFβ1通过与肝素结合的呈递通过隔离额外的内源性产生的血管生成因子来改善分化的CPC功能。最后，我们证明，TGFβ1和肝素的HyA水凝胶可以促进CPC的生存皮下植入到小鼠后肢，并鼓励他们参与随后的新生血管反应，包括血管已经与宿主的血管。
We have generated a bioinspired tunable system of hyaluronic acid (HyA)-based hydrogels for Matrix-Assisted Cell Transplantation (MACT). With this material, we have independently evaluated matrix parameters such as adhesion peptide density, mechanical properties, and growth factor sequestering capacity, to engineer an environment that imbues donor cells with a milieu that promotes survival and engraftment with host tissues after transplantation. Using a versatile population of Sca-1+/CD45− cardiac progenitor cells (CPCs), we demonstrated that the addition of heparin in the HyA hydrogels was necessary to coordinate the presentation of TGFβ1 and to support the trophic functions of the CPCs via endothelial cell differentiation and vascular like tubular network formation. Presentation of exogenous TGFβ1 by binding with heparin improved differentiated CPC function by sequestering additional endogenously-produced angiogenic factors. Finally, we demonstrated that TGFβ1 and heparin-containing HyA hydrogels can promote CPC survival when implanted subcutaneously into murine hind-limbs and encouraged their participation in the ensuing neovascular response, including blood vessels that had anastomosed with the host’s blood vessels.
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