Periadventitial Adipose-Derived Stem Cell Treatment Halts Elastase-Induced Abdominal Aortic Aneurysm Progression

Abstract

Aim: Demonstrate that periadventitial delivery of adipose-derived mesenchymal stem cells (ADMSCs) slows aneurysm progression in an established murine elastase-perfusion model of abdominal aortic aneurysm (AAA). Materials & methods: AAAs were induced in C57BL/6 mice using porcine elastase. During elastase perfusion, a delivery device consisting of a subcutaneous port, tubing and porous scaffold was implanted. Five days after elastase perfusion, 100,000 ADMSCs were delivered through the port to the aorta. After sacrifice at day 14, analyzed metrics included aortic diameter and structure of aortic elastin. Results: ADMSC treated aneurysms had a smaller diameter and less fragmented elastin versus saline controls. Conclusion: Periadventitial stem cell delivery prevented the expansion of an established aneurysm between days 5 and 14 after elastase perfusion.

Keywords::

• abdominal aortic aneurysm
• adipose-derived stem cells
• elastin
• regeneration

Acknowledgements

The authors would like to thank the Center for Biologic Imaging at the University of Pittsburgh for their technical assistance with acquiring multi-photon and immunofluorescence images, and Jayashree Rao for her staining and imaging of immunofluorescence samples. They would also like to thank Kacey Marra for her consultation about the use and sourcing of ADMSCs.

Disclaimer

The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.

Financial & competing interests disclosure

The authors would like to disclose funding support by the National Institutes of Health (Cardiovascular Bioengineering Training Program T32 HL076124 and Biomechanics in Regenerative Medicine T32 EB000392 to KJ Blose, HL086418 to DA Vorp, AG037120 to JA Curci) and the Peripheral Vascular Surgical Society (Academic Award 2012–2013 to JA Curci). This material is based upon work supported (or supported in part) by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (JA Curci). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The authors would like to disclose funding support by the National Institutes of Health (Cardiovascular Bioengineering Training Program T32 HL076124 and Biomechanics in Regenerative Medicine T32 EB000392 to KJ Blose, HL086418 to DA Vorp, AG037120 to JA Curci) and the Peripheral Vascular Surgical Society (Academic Award 2012–2013 to JA Curci). This material is based upon work supported (or supported in part) by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (JA Curci). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.