J Vet Sci.  2024 Nov;25(6):e80. 10.4142/jvs.24163.

Medication effects on pulmonary thromboembolism in mice intravenously transplanted with canine adipose tissue-derived mesenchymal stem cells

Affiliations
  • 1Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
  • 2Department of Veterinary Obstetrics and Theriogenology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
  • 3Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul 05029, Korea
  • 4Department of Anatomy, College of Veterinary Medicine, and Veterinary Science Research Institute, Konkuk University, Seoul 05030, Korea
  • 5Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
  • 6KU Center for Animal Blood Medical Science, Konkuk University, Seoul 05029, Korea

Abstract

Importance
The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is a promising regenerative therapy, but it can lead to severe complications, including pulmonary thromboembolism (PTE).
Objective
As part of an ongoing study, this study examined the impact of medications, such as heparin, aspirin, and sodium nitroprusside (SNP), on the factors linked to PTE after an intravenous injection of canine mesenchymal stem cell into experimental animals.
Methods
Fluorescently labeled canine AdMSCs were administered intravenously into the tail veins of five-week-old male BALB/c hairless mice. This study compared the survival rates, biodistribution, platelet counts, D-dimer levels, and histological examination results among the drug treatment experimental and the control groups.
Results
The final survival rates in the SNP, control aspirin, and heparin groups were 25%, 33%, 50%, and 100%, respectively. Ex vivo imaging confirmed fluorescence exclusively in the lungs of all subjects who died during the injection, with no fluorescence detected in the other organs. On the other hand, in the heparin experimental group, the surviving individuals exhibited fluorescence in the lungs and the liver on day one. Histological biopsies revealed PTE in all deceased individuals within the medication experimental groups (p = 0.029).
Conclusions and Relevance
Heparin was highly effective, with no PTE-related deaths observed when used alongside cell injections. Aspirin revealed moderate effectiveness, surpassing the control group. On the other hand, the efficacy of SNP was inferior to that of the other two drugs.

Keyword

Intravenous injection; mesenchymal stem cells (MSCs); heparin; aspirin; sodium nitroprusside (SNP)
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