Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments.
Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments.
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DOI：
10.1002/sctm.17-0157
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发表时间：
2018-03
影响因子：
6
通讯作者：
Almeida-Porada G
中科院分区：
文献类型：
--
作者：
Mokhtari S;Baptista PM;Vyas DA;Freeman CJ;Moran E;Brovold M;Llamazares GA;Lamar Z;Porada CD;Soker S;Almeida-Porada G
尽管在脐带血衍生的造血干/祖细胞（CB-HSPC）的离体扩增方面取得了进展，但关于从单个单位获得足够数量的细胞以治疗青少年或成年患者的能力仍然存在挑战。我们和其他人已经表明，CB-HSPC可以在二维（2D）培养物中离体扩增，但更原始干细胞的绝对百分比随时间推移而下降。在发育过程中，胎肝是HSPC扩增的主要部位。因此，我们在体外研究了原始HSPC与替代胎肝环境相互作用的结果。我们比较了由天然三维肝脏细胞外基质（3D-ECM）制成的生物工程肝脏构建体与其各自的2D培养对应物，其中3D-ECM接种有成肝细胞、胎肝源性（LvSt）或骨髓源性基质细胞。我们表明，在3D-ECM支架中包含细胞组分对于维持培养物中的HSPC活力是必要的，并且无论使用何种微环境，3D-ECM结构都导致维持更原始的HSPC亚群，如通过流式细胞术和集落形成测定所确定的。此外，我们表明，扩展的时间和程度取决于所使用的生物组分，LvSt提供了原始CB HSPC的保存和细胞分化之间的最佳平衡。干细胞转化医学2018;7：271-282
Despite advances in ex vivo expansion of cord blood‐derived hematopoietic stem/progenitor cells (CB‐HSPC), challenges still remain regarding the ability to obtain, from a single unit, sufficient numbers of cells to treat an adolescent or adult patient. We and others have shown that CB‐HSPC can be expanded ex vivo in two‐dimensional (2D) cultures, but the absolute percentage of the more primitive stem cells decreases with time. During development, the fetal liver is the main site of HSPC expansion. Therefore, here we investigated, in vitro, the outcome of interactions of primitive HSPC with surrogate fetal liver environments. We compared bioengineered liver constructs made from a natural three‐dimensional‐liver‐extracellular‐matrix (3D‐ECM) seeded with hepatoblasts, fetal liver‐derived (LvSt), or bone marrow‐derived stromal cells, to their respective 2D culture counterparts. We showed that the inclusion of cellular components within the 3D‐ECM scaffolds was necessary for maintenance of HSPC viability in culture, and that irrespective of the microenvironment used, the 3D‐ECM structures led to the maintenance of a more primitive subpopulation of HSPC, as determined by flow cytometry and colony forming assays. In addition, we showed that the timing and extent of expansion depends upon the biological component used, with LvSt providing the optimal balance between preservation of primitive CB HSPC and cellular differentiation. Stem Cells Translational Medicine 2018;7:271–282
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影响因子：
3.3
作者：
da Silva, Claudia Lobato;Goncalves, Raquel;Cabral, Joaquim M. S.
通讯作者：
Cabral, Joaquim M. S.
影响因子：
4
作者：
Andrade, Pedro Z.;da Silva, Claudia Lobato;Cabral, Joaquim M. S.
通讯作者：
Cabral, Joaquim M. S.
影响因子：
6
作者：
Gori JL;Butler JM;Kunar B;Poulos MG;Ginsberg M;Nolan DJ;Norgaard ZK;Adair JE;Rafii S;Kiem HP
通讯作者：
Kiem HP
DOI：
10.1089/ten.tec.2016.0329
发表时间：
2017-04
期刊：
Tissue engineering. Part C, Methods
影响因子：
--
作者：
Futrega K;Atkinson K;Lott WB;Doran MR
通讯作者：
Doran MR
影响因子：
4
作者：
Campbell, Timothy B.;Hangoc, Giao;Broxmeyer, Hal E.
通讯作者：
Broxmeyer, Hal E.