Umbilical cord mesenchymal stromal cells in serum-free defined medium display an improved safety profile.
Umbilical cord mesenchymal stromal cells in serum-free defined medium display an improved safety profile.
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脐带间充质基质细胞在无血清定义培养基中显示出改进的安全性。
DOI：
10.1186/s13287-023-03604-0
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发表时间：
2023-12-12
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
在将基于细胞的产品转化为临床应用之前，需要在临床前研究中进行安全性评价以确认。我们之前开发了一种无血清、无异种和化学成分确定的培养基（S&XFM-CD）用于临床级脐带来源的MSC（UCMSCs）的衍生，并证明了腹腔内给予S&XFM-CD（UCMSCS&XFM−CD）中的UCMSCs比含血清培养基（SCM，UCMSCSCM）中的UCMSCs表现出更好的治疗效果。然而，在临床应用之前，应对腹腔内UCMSCS和XFM−CD治疗的安全性进行全面研究。本研究通过大鼠一般生命体征、血常规、血生化、T细胞亚群、血清细胞因子、重要器官病理、抗体产生和人类特异性基因表达等指标，比较腹腔移植UCMSCS&XFM−CD与UCMSCSCM的毒性、免疫原性和生物分布。比较UCMSCS&XFM−CD与UCMSCSCM在裸鼠体内的致瘤性和促瘤作用。我们证实，腹腔内移植UCMSCS和XFM−CD或UCMSCSCM对实验大鼠的体重、体温、收缩压、舒张压、心率、血常规、T淋巴细胞亚群和血清细胞因子均未引起显著变化，且无明显的组织病理学改变。UCMSCS和XFM−CD不产生抗体，而UCMSCSCM产生牛血清白蛋白（80%）和载脂蛋白B-100（60%）抗体的机会非常高。此外，腹膜内注射UCMSCS和XFM−CD不太可能被肺部阻塞，并且比UCMSCSCM更容易迁移到肾脏和结肠组织。此外，UCMSCS和XFM−CD或UCMSCSCM没有显示出明显的致瘤活性。UCMSCS和XFM−CD延长了KM 12 SM细胞的成瘤时间，降低了肿瘤发生率。总之，我们的数据表明，UCMSCS和XFM−CD显示出更好的安全性能，并鼓励在未来的临床试验中使用。在线版本包含补充材料，可通过10.1186/s13287-023-03604-0获得。
Safety evaluations in preclinical studies are needed to confirm before translating a cell-based product into clinical application. We previously developed a serum-free, xeno-free, and chemically defined media (S&XFM–CD) for the derivation of clinical-grade umbilical cord-derived MSCs (UCMSCs), and demonstrated that intraperitoneal administration of UCMSCs in S&XFM–CD (UCMSCS&XFM−CD) exhibited better therapeutic effects than UCMSCs in serum-containing media (SCM, UCMSCSCM). However, a comprehensive investigation of the safety of intraperitoneal UCMSCS&XFM−CD treatment should be performed before clinical applications. In this study, the toxicity, immunogenicity and biodistribution of intraperitoneally transplanted UCMSCS&XFM−CD were compared with UCMSCSCM in rats via general vital signs, blood routine, blood biochemistry, subsets of T cells, serum cytokines, pathology of vital organs, antibody production and the expression of human-specific gene. The tumorigenicity and tumor-promoting effect of UCMSCS&XFM−CD were compared with UCMSCSCM in nude mice. We confirmed that intraperitoneally transplanted UCMSCS&XFM−CD or UCMSCSCM did not cause significant changes in body weight, temperature, systolic blood pressure, diastolic blood pressure, heart rate, blood routine, T lymphocyte subsets, and serum cytokines, and had no obvious histopathology change on experimental rats. UCMSCS&XFM−CD did not produce antibodies, while UCMSCSCM had very high chance of antibody production to bovine serum albumin (80%) and apolipoprotein B-100 (60%). Furthermore, intraperitoneally injected UCMSCS&XFM−CD were less likely to be blocked by the lungs and migrated more easily to the kidneys and colon tissue than UCMSCSCM. In addition, UCMSCS&XFM−CD or UCMSCSCM showed no obvious tumorigenic activity. Finally, UCMSCS&XFM−CD extended the time of tumor formation of KM12SM cells, and decreased tumor incidence than that of UCMSCSCM. Taken together, our data indicate that UCMSCS&XFM−CD display an improved safety performance and are encouraged to use in future clinical trials. The online version contains supplementary material available at 10.1186/s13287-023-03604-0.
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