Actin cytoskeletal disruption following cryopreservation alters the biodistribution of human mesenchymal stromal cells in vivo.
Actin cytoskeletal disruption following cryopreservation alters the biodistribution of human mesenchymal stromal cells in vivo.
复制标题
DOI：
10.1016/j.stemcr.2014.05.003
复制
发表时间：
2014-07-08
影响因子：
5.9
通讯作者：
Copland, Ian B.
中科院分区：
文献类型：
--
作者：
Chinnadurai, Raghavan;Garcia, Marco A.;Sakurai, Yumiko;Lam, Wilbur A.;Kirk, Allan D.;Galipeau, Jacques;Copland, Ian B.
间充质基质细胞已显示出临床前景;然而，治疗反应的变化是一个持续的问题。我们先前证明了MSC在解冻后功能性地休克。在这里，我们研究了这种冷冻保存/解冻缺陷是否也影响了骨髓间充质干细胞的输注后生物分布特性。在静态和生理流动下，与活性培养中的活MSC相比，从冷冻保存中解冻的MSC分别与纤连蛋白（减少40%）和人内皮细胞（减少80%）结合较差。这种减少与解冻后MSC中细胞骨架F-肌动蛋白含量减少（减少60%）相关。在体内，活的人MSC可以检测到小鼠肺组织长达24小时，而解冻的MSC是检测不到的。同样，肌动蛋白细胞骨架被化学破坏的活MSC在输注后24小时检测不到。我们的数据表明，解冻后冷冻保存的MSC不同于活的MSC。这种区别可能会显着影响MSC作为细胞治疗剂的效用。解冻后，MSC立即显示减弱的结合和植入潜力解冻后，MSC显示有缺陷的肌动蛋白聚合破坏MSC中的肌动蛋白细胞骨架复制解冻后MSC植入缺陷解冻后48小时培养恢复MSC恢复体内植入潜力Copland及其同事评估了冷冻保存和解冻过程是否影响人MSC的输注后生物分布特性。体外和体内分析表明，骨髓间充质干细胞解冻后立即结合缺陷，这与细胞骨架F-肌动蛋白含量减少有关。这些数据支持使用活的MSC而不是冷冻保存的解冻后MSC进行临床评价的想法。
Mesenchymal stromal cells have shown clinical promise; however, variations in treatment responses are an ongoing concern. We previously demonstrated that MSCs are functionally stunned after thawing. Here, we investigated whether this cryopreservation/thawing defect also impacts the postinfusion biodistribution properties of MSCs. Under both static and physiologic flow, compared with live MSCs in active culture, MSCs thawed from cryopreservation bound poorly to fibronectin (40% reduction) and human endothelial cells (80% reduction), respectively. This reduction correlated with a reduced cytoskeletal F-actin content in post-thaw MSCs (60% reduction). In vivo, live human MSCs could be detected in murine lung tissues for up to 24 hr, whereas thawed MSCs were undetectable. Similarly, live MSCs whose actin cytoskeleton was chemically disrupted were undetectable at 24 hr postinfusion. Our data suggest that post-thaw cryopreserved MSCs are distinct from live MSCs. This distinction could significantly affect the utility of MSCs as a cellular therapeutic. Immediately after thawing, MSCs display attenuated binding and engraftment potential Immediately after thawing, MSCs display defective actin polymerization Disrupting actin cytoskeleton in MSCs replicates post-thaw MSC engraftment defect A 48 hr culture recovery of MSCs post-thaw restores in vivo engraftment potential Copland and colleagues evaluated whether the cryopreservation and thawing process impacts the postinfusion biodistribution properties of human MSCs. In vitro and in vivo analyses demonstrated a binding defect of MSCs immediately after thawing that was correlated with a reduced cytoskeletal F-actin content. These data support the idea of utilizing live MSCs rather than cryopreserved post-thaw MSCs for clinical evaluation.
登录
查看更多内容
影响因子：
1.7
作者：
Fortunato, Adriana;Leo, Rita;Liguori, Francesca
通讯作者：
Liguori, Francesca
影响因子：
3.3
作者：
Crop, Meindert J.;Korevaar, Sander S.;Hoogduijn, Martin J.
通讯作者：
Hoogduijn, Martin J.
影响因子：
20.1
作者：
Huang J;Zhang Z;Guo J;Ni A;Deb A;Zhang L;Mirotsou M;Pratt RE;Dzau VJ
通讯作者：
Dzau VJ
DOI：
10.1007/978-1-60761-999-4_13
发表时间：
2011-01-01
期刊：
MESENCHYMAL STEM CELL ASSAYS AND APPLICATIONS
影响因子：
--
作者：
Haack-Sorensen, Mandana;Kastrup, Jens
通讯作者：
Kastrup, Jens
影响因子：
7.5
作者：
Li Q;Wang Y;Deng Z
通讯作者：
Deng Z