Multimodal assessment of mesenchymal stem cell therapy for diabetic vascular complications

Jamila Hedhli, Christian J. Konopka, Sarah Schuh, Hannah Bouvin, John A. Cole, Heather D. Huntsman, Kristopher A. Kilian, Iwona T. Dobrucki, Marni D. Boppart, Lawrence W. Dobrucki

Research output: Contribution to journalArticlepeer-review


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 αVß3-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.

Original languageEnglish (US)
Pages (from-to)3876-3888
Number of pages13
Issue number16
StatePublished - 2017


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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)


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