Pulmonary passage of canine adipose tissue-derived mesenchymal stem cells through intravenous transplantation in mouse model.

Abstract

Importance: The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is an attractive treatment option. On the other hand, it can result in severe complications, including pulmonary thromboembolism (PTE).

Objective: The present study assessed the occurrence of PTE after the intravenous infusion of canine AdMSCs (cAdMSCs) into experimental animals.

Methods: Five-week-old male BALB/c hairless mice were categorized into groups labeled A to G. In the control group (A), fluorescently stained 2 × 10⁶ cAdMSCs were diluted in 200 μL of suspension and injected into the tail vein as a single bolus. The remaining groups included the following: group B with 5 × 10⁶ cells, group C with 3 × 10⁶ cells, group D with 1 × 10⁶ cells, group E with 1 × 10⁶ cells injected twice with a one-day interval, group F with 2 × 10⁶ cells in 100 μL of suspension, and group G with 2 × 10⁶ cells in 300 μL of suspension.

Results: Group D achieved a 100% survival rate, while none of the subjects in groups B and C survived (p = 0.002). Blood tests revealed a tendency for the D-dimer levels to increase as the cell dose increased (p = 0.006). The platelet count was higher in the low cell concentration groups and lower in the high cell concentration groups (p = 0.028). A histological examination revealed PTE in most deceased subjects (96.30%).

Conclusions and relevance: PTE was verified, and various variables were identified as potential contributing factors, including the cell dose, injection frequency, and suspension volume.