Cruz Fernanda F, Borg Zachary D, Goodwin Meagan, Sokocevic Dino, Wagner Darcy, McKenna David H, Rocco Patricia R M, Weiss Daniel J
Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA
Stem Cells Transl Med. 2015 Jun;4(6):615-24. doi: 10.5966/sctm.2014-0268. Epub 2015 Apr 29.
Recent data suggest that freshly thawed previously frozen mesenchymal stromal cells (MSCs) may not have the same effectiveness or breadth of anti-inflammatory activities as do continuously cultured MSCs. This has significant implications for clinical use, in which many infusion schemes use frozen cells thawed at the bedside for administration. The available data, however, predominantly evaluate in vitro MSC properties, and so far there has been limited in vivo analysis. To further assess this issue, we compared freshly thawed (thawed) versus continuously cultured (fresh) human bone marrow-derived MSC (hMSC) administration in a mouse model of mixed Th2/Th17 allergic airway inflammation induced by Aspergillus hyphal extract (AHE) exposures in immunocompetent C57Bl/6 mice. Control cell populations included fresh versus thawed murine bone marrow-derived MSCs (mMSCs) and human lung fibroblasts (HLFs). Systemic administration of both thawed and fresh hMSCs and mMSCs, but not HLFs, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE-provoked increases in airway hyper-reactivity, lung inflammation, and antigen-specific CD4 T-cell Th2 and Th17 phenotype. Notably, there was no difference in effects of fresh versus thawed hMSCs or mMSCs on any outcome measured except for some variability in the effects on the bronchoalveolar lavage fluid composition. These results demonstrated potent xenogeneic effects of human MSCs in an immunocompetent mouse model of allergic airways inflammation and that thawed MSCs are as effective as fresh MSCs. The question of fresh versus thawed MSC effectiveness needs to be investigated carefully and may differ in different in vivo disease-specific models.
This study addressed whether freshly thawed mesenchymal stromal cells (MSCs) are as effective in in vivo settings as those that have been continuously cultured. It also provided further data demonstrating that xenogeneic use of MSCs in immunocompetent mice is as effective as murine MSCs. This information provides further support and direction for potential clinical use of MSCs in patients with severe asthma.
近期数据表明，刚解冻的先前冷冻的间充质基质细胞（MSC）可能不像持续培养的MSC那样具有相同的抗炎活性效力或广度。这对临床应用具有重大影响，因为许多输注方案使用在床边解冻的冷冻细胞进行给药。然而，现有数据主要评估体外MSC特性，迄今为止体内分析有限。为了进一步评估这个问题，我们在免疫活性C57Bl/6小鼠中，比较了刚解冻（解冻）与持续培养（新鲜）的人骨髓来源的MSC（hMSC）在由烟曲霉菌丝提取物（AHE）暴露诱导的混合Th2/Th17过敏性气道炎症小鼠模型中的给药情况。对照细胞群体包括新鲜与解冻的鼠骨髓来源的MSC（mMSC）和人肺成纤维细胞（HLF）。在先前致敏的小鼠抗原攻击开始时，全身给予解冻和新鲜的hMSC和mMSC，但不给予HLF，可显著改善AHE诱发的气道高反应性、肺部炎症以及抗原特异性CD4 T细胞Th2和Th17表型的增加。值得注意的是，新鲜与解冻的hMSC或mMSC对任何测量结果的影响没有差异，除了对支气管肺泡灌洗液成分的影响存在一些变异性。这些结果证明了人MSC在免疫活性小鼠过敏性气道炎症模型中的强大异种效应，并且解冻的MSC与新鲜的MSC一样有效。新鲜与解冻的MSC有效性问题需要仔细研究，并且在不同的体内疾病特异性模型中可能有所不同。
本研究探讨了刚解冻的间充质基质细胞（MSC）在体内环境中是否与持续培养的细胞一样有效。它还提供了进一步的数据，证明在免疫活性小鼠中异种使用MSC与鼠MSC一样有效。这些信息为严重哮喘患者中MSC的潜在临床应用提供了进一步的支持和指导。
