Restoring Vasculogenic Potential of Endothelial Cells from Diabetic Patients Through Spheroid Formation

Charlotte E. Vorwald, Kaitlin C. Murphy, Jonathan K Leach

Research output: Contribution to journalArticle

Abstract

Introduction: Diabetes is an emerging epidemic in the developing world and represents a major risk factor for cardiovascular disease. Among other issues, patients with diabetes suffer from diminished endothelial cell (EC) function, which contributes to impaired vasculogenesis and recovery from ischemic insult. The formation of cells into three-dimensional spheroids promotes cell survival and activates key signaling pathways through the upregulation of cell–cell contacts, providing an opportunity to overcome shortcomings associated with individual autologous cells. Methods: We hypothesized that forming human microvascular endothelial cells (HMVECs) from diabetic patients into spheroids would restore their vasculogenic potential following upregulation of these cell–cell interactions. HMVEC spheroids were formed and suspended in fibrin gels to quantify vasculogenic potential. Results: Individual HMVECs from diabetic patients exhibited similar proliferative and chemotactic potential to cells from healthy donors but reduced tubulogenesis. HMVEC spheroids formed from diabetic donors formed more sprouts than spheroids from healthy donors, and more sprouts than individual cells from either population. Compared to cells from healthy donors, sprout formation was more efficiently abrogated in HMVECs from diabetic patients by blocking matrix metalloproteinase activity. Conclusions: This study demonstrates a promising approach for restoring the diminished vasculogenic potential of endothelial cells in diabetic patients.

Original languageEnglish (US)
Pages (from-to)267-278
Number of pages12
JournalCellular and Molecular Bioengineering
Volume11
Issue number4
DOIs
StatePublished - Aug 1 2018

Fingerprint

Endothelial Cells
Endothelial cells
Cell
Tissue Donors
Diabetes
Medical problems
Up-Regulation
Cells
Signaling Pathways
Risk Factors
Fibrin
Matrix Metalloproteinases
Cell Survival
Quantify
Cardiovascular Diseases
Gels
Recovery
Human
Contact
Three-dimensional

Keywords

  • Angiogenesis
  • Diabetes
  • Ischemia
  • Spheroid
  • Tissue engineering

ASJC Scopus subject areas

  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Restoring Vasculogenic Potential of Endothelial Cells from Diabetic Patients Through Spheroid Formation. / Vorwald, Charlotte E.; Murphy, Kaitlin C.; Leach, Jonathan K.

In: Cellular and Molecular Bioengineering, Vol. 11, No. 4, 01.08.2018, p. 267-278.

Research output: Contribution to journalArticle

Vorwald, Charlotte E. ; Murphy, Kaitlin C. ; Leach, Jonathan K. / Restoring Vasculogenic Potential of Endothelial Cells from Diabetic Patients Through Spheroid Formation. In: Cellular and Molecular Bioengineering. 2018 ; Vol. 11, No. 4. pp. 267-278.
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