Theranostics 2017; 7(16):3876-3888. doi:10.7150/thno.19547

Research Paper

Multimodal Assessment of Mesenchymal Stem Cell Therapy for Diabetic Vascular Complications

Jamila Hedhli1, 2, Christian J. Konopka1, 2, Sarah Schuh2, Hannah Bouvin1, John A. Cole3, Heather D. Huntsman1, 4, Kristopher A. Kilian2, Iwona T. Dobrucki1, Marni D. Boppart1, 4, Lawrence W. Dobrucki1, 2✉

1. Beckman Institute for Advanced Science and Technology, Urbana, IL;
2. Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL;
3. Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL;
4. Department of Kinesiology, University of Illinois at Urbana-Champaign, Urbana, IL.

Abstract

Peripheral arterial disease (PAD) is a debilitating complication of diabetes mellitus (DM) that leads to thousands of injuries, amputations, and deaths each year. The use of mesenchymal stem cells (MSCs) as a regenerative therapy holds the promise of regrowing injured vasculature, helping DM patients live healthier and longer lives. We report the use of muscle-derived MSCs to treat surgically-induced hindlimb ischemia in a mouse model of type 1 diabetes (DM-1). We serially evaluate several facets of the recovery process, including αVβ3-integrin expression (a marker of angiogenesis), blood perfusion, and muscle function. We also perform microarray transcriptomics experiments to characterize the gene expression states of the MSC-treated is- chemic tissues, and compare the results with those of non-ischemic tissues, as well as ischemic tissues from a saline-treated control group.

The results show a multifaceted impact of mMSCs on hindlimb ischemia. We determined that the angiogenic activity one week after mMSC treatment was enhanced by approximately 80% relative to the saline group, which resulted in relative increases in blood perfusion and muscle strength of approximately 42% and 1.7-fold, respectively. At the transcriptomics level, we found that several classes of genes were affected by mMSC treatment. The mMSCs appeared to enhance both pro-angiogenic and metabolic genes, while suppressing anti-angiogenic genes and certain genes involved in the inflammatory response. All told, mMSC treatment appears to exert far-reaching effects on the microenvironment of ischemic tissue, enabling faster and more complete recovery from vascular occlusion.

Keywords: Angiogenesis, PET-CT, Dimeric-cRGD, Multimodal imaging, Peripheral arterial disease (PAD), Diabetes, Muscle-derived mesenchymal stem cells (mMSCs).

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How to cite this article:
Hedhli J, Konopka CJ, Schuh S, Bouvin H, Cole JA, Huntsman HD, Kilian KA, Dobrucki IT, Boppart MD, Dobrucki LW. Multimodal Assessment of Mesenchymal Stem Cell Therapy for Diabetic Vascular Complications. Theranostics 2017; 7(16):3876-3888. doi:10.7150/thno.19547. Available from http://www.thno.org/v07p3876.htm