Umbilical cord mesenchymal stromal cells in serum-free defined medium display an improved safety profile
Xiaoyun Wu1,2,3,4, Zhijie Ma5, Yuxiao Yang3,6
1Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, People's Republic of China.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
Taken together, our data indicate that UCMSCS&XFM-CD display an improved safety performance and are encouraged to use in future clinical trials.
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