Department of Bioengineering and iBB, Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.
J Cell Physiol. 2020 Oct;235(10):7224-7238. doi: 10.1002/jcp.29622. Epub 2020 Feb 9.
Mesenchymal stromal cells (MSCs) have been widely exploited for the treatment of several conditions due to their intrinsic regenerative and immunomodulatory properties. MSC have demonstrated to be particularly relevant for the treatment of ischemic diseases, where MSC-based therapies can stimulate angiogenesis and induce tissue regeneration. Regardless of the condition targeted, recent analyses of MSC-based clinical trials have demonstrated limited benefits indicating a need to improve the efficacy of this cell product. Preconditioning MSC ex vivo through microenvironment modulation was found to improve MSC survival rate and thus prolong their therapeutic effect. This workstudy aims at enhancing the in vitro angiogenic capacity of a potential MSC-based medicinal product by comparing different sources of MSC and culture conditions. MSC from three different sources (bone marrow [BM], adipose tissue [AT], and umbilical cord matrix [UCM]) were cultured with xenogeneic-/serum-free culture medium under static conditions and their angiogenic potential was studied. Results indicated a higher in vitro angiogenic capacity of UCM MSC, compared with cells derived from BM and AT. Physicochemical preconditioning of UCM MSC through a microcarrier-based culture platform and low oxygen concentration (2% O , compared with atmospheric air) increased the in vitro angiogenic potential of the cultured cells. Envisaging the clinical manufacturing of an allogeneic, off-the-shelf MSC-based product, preconditioned UCM MSC maintain the angiogenic gene expression profile upon cryopreservation and delivery processes in the conditions of our study. These results are expected to contribute to the development of MSC-based therapies in the context of angiogenesis.
间充质基质细胞 (MSCs) 因其固有再生和免疫调节特性而被广泛用于治疗多种疾病。MSC 已被证明对缺血性疾病的治疗特别相关，基于 MSC 的治疗方法可以刺激血管生成并诱导组织再生。无论针对的是哪种疾病，最近对基于 MSC 的临床试验的分析表明，疗效有限，表明需要提高这种细胞产品的疗效。体外通过微环境调节预处理 MSC 被发现可以提高 MSC 的存活率，从而延长其治疗效果。这项工作旨在通过比较不同来源的 MSC 和培养条件来提高潜在基于 MSC 的药物产品的体外血管生成能力。在静态条件下，使用异种血清-free 培养基培养来自三个不同来源的 MSC（骨髓 [BM]、脂肪组织 [AT] 和脐带基质 [UCM]），并研究其血管生成潜力。结果表明，与源自 BM 和 AT 的细胞相比，UCM MSC 的体外血管生成能力更高。通过微载体培养平台和低氧浓度（2% O ，与大气相比）对 UCM MSC 进行物理化学预处理，增加了培养细胞的体外血管生成潜力。考虑到同种异体、现成的基于 MSC 的产品的临床制造，在我们研究的条件下，经过预培养的 UCM MSC 在冷冻保存和输送过程中保持了血管生成基因表达谱。这些结果有望为血管生成背景下的 MSC 治疗的发展做出贡献。
