Xenotransplantation of human unrestricted somatic stem cells in a pig model of acute myocardial infarction

Xenotransplantation. 2013 Mar-Apr;20(2):110-22. doi: 10.1111/xen.12026. Epub 2013 Mar 13.

Abstract

Background: Stem cell therapy may help restore cardiac function after acute myocardial infarction (AMI), but the optimal therapeutic cell type has not been identified.

Methods: We examined the effects of CD34-/CD45- human unrestricted somatic stem cells (USSCs) in pigs (n = 30) with an AMI created by a 90-min occlusion of the left anterior descending coronary artery. Pigs were randomly assigned to receive either USSCs (302 ± 23 × 10(6) cells) or phosphate-buffered saline via 15 NOGA-guided transendocardial injections 10 days after AMI. Cyclosporine A (10 mg/kg orally, twice a day) was started in all pigs 3 days before control or cell treatment. Cardiac function was assessed by echocardiography before injection and at 4 and 8 weeks after treatment. Serum titers for pig IgG antibodies against USSCs were also measured at these time points and before AMI.

Results: Compared with control pigs, USSC-treated pigs showed no significant differences in any of the functional parameters examined. USSC-treated pigs showed variable increases in anti-USSC IgG antibody titers in the blood and chronic inflammatory infiltrates at the cell injection sites. Immunohistochemical studies of the injection sites using human anti-mitochondrial antibodies failed to detect implanted USSCs.

Conclusions: We conclude that human USSCs did not improve cardiac function in a pig model of AMI. Cell transplantation in a xenogeneic setting may obscure the benefits of stem cell therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Heterophile / blood
  • Antibodies, Heterophile / immunology
  • Antigens, Heterophile / immunology
  • Cells, Cultured
  • Cord Blood Stem Cell Transplantation / methods*
  • Disease Models, Animal
  • Heart Function Tests
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Mitochondria / immunology
  • Myocardial Infarction / immunology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / transplantation*
  • Random Allocation
  • Sus scrofa
  • Transplantation, Heterologous / immunology
  • Transplantation, Heterologous / methods*
  • Treatment Failure

Substances

  • Antibodies, Heterophile
  • Antigens, Heterophile
  • Immunosuppressive Agents