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.

间充质基质细胞已显示出临床前景；然而，治疗反应的差异是一个持续关注的问题。我们之前已经证明 MSC 在解冻后功能性昏迷。在这里，我们研究了这种冷冻保存/解冻缺陷是否也会影响 MSCs 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-肌动蛋白含量的减少有关（减少 60%）。在体内，可在鼠肺组织中检测到活人 MSCs 长达 24 小时，而解冻的 MSCs 检测不到。相似地，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 MSCs 与活的 MSCs 不同。这种区别可能会显着影响 MSC 作为细胞治疗剂的效用。