Safety study of allogeneic mesenchymal stem cell therapy in animal model

Abstract

Intravenous (IV) infusion of mesenchymal stem cells (MSCs) from nascent tissues like Wharton's Jelly of the umbilical cord is reported to offer therapeutic effects against chronic diseases. However, toxicological data essential for the clinical application of these cells are limited. Thus, this study aimed to determine the safety of IV infusion of Wharton's Jelly derived MSCs (WJ-MSCs) in rats. Fifteen male Sprague-Dawley rats were randomised into the control or treatment group. Each group received an equal volume of saline or WJ-MSC (10 × 10⁶ cell/kg) respectively. The animals were evaluated for physical, biochemical and haematological changes at Week 0, 2, 4, 8 and 12 during the 12-week study. Acute toxicity was performed during Week 2 and sub-chronic toxicity during Week 12. At the end of the study, the relative weight of organs was calculated and histology was performed for lung, liver, spleen and kidney. The findings from physical, serum biochemistry and complete blood count demonstrated no statistically significant differences between groups. However, pathological evaluation reported minor inflammation in the lungs for all groups, but visible healing and resolution of inflammation were observed in the treatment group only. Additionally, the histological images of the treatment group had significantly improved pulmonary structures compared to the control group. In summary, the IV administration of WJ-MSC was safe in the rats. Further studies are needed to determine the long-term safety of the WJ-MSC in both healthy and diseased animal models.

Keywords: Intravenous; Mesenchymal stem cell; Safety; Toxicity; Umbilical cord; Wharton's Jelly.

Graphical abstract

Fig. 1

(from left to right) [A] Physical measurements of Body Weight, Body Length, Abdominal Circumference, Food Intake, Water Intake and BMI. [B] Serum biochemistry of ALP, AST, ALT, CHOL, AMY, CREAT and LDH. [C] Whole blood profile of RBC, Hb, MCV, MCHC, PCV, WBC, BAND N, NEUTRO, LYMPH, MONO, EOSIN and PLT. Data was presented as mean ± SEM (n = 6 rodent per group) for the control and treatment group for a study period 0, 2, 4, 8 and 12 weeks. Superscripts indicate significant differences of data: ∗p < 0.05 to earliest or baseline value; # (p < 0.05) between groups at the same time period.

Fig. 2

Post-mortem assessment of control and treatment animals after euthanasia (from left to right). [A] Relative weight of lungs, liver, kidneys, spleen, bone, heart, muscle and gut; Data was presented as mean ± SEM. Superscripts indicate significant differences of data: ∗p < 0.05 between groups. [B] H&E-stained lung, liver, kidney and spleen for control (Week 12) and treatment group for acute toxicity (Week 2) and sub-chronic toxicity (Week 12). Black arrows indicate the specific region for lung pathological condition. Images were captured at magnification of 10x or 40x with scale bar, 100 μm.