Combination therapy of autologous adipose mesenchymal stem cell-enriched, high-density lipoaspirate and topical timolol for healing chronic wounds

Larissa N Larsen, Catherine N. Tchanque-Fossuo, Farzam Gorouhi, David Boudreault, Chuong Nguyen, Jaime J. Fuentes, Robert W. Crawford, Sara E. Dahle, Thomas Whetzel, Roslyn Rivkah Isseroff

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Chronic venous leg ulcers are profoundly debilitating and result in billions in health care expenditure. Thus, there is a quest for engineered and innovative approaches. Herein we present a 63-year-old patient with a 30 year history of venous stasis and left lower extremity ulcers, which have been refractory to standard of care, anticoagulation and venous stripping. The medial ulcer was treated with transplantation of autologous adipose mesenchymal stem cell (AMSC)-enriched, high-density lipoaspirate (HDL) on OASIS wound matrix and compression therapy. The lateral ulcer was treated as a control with standard debridement and compression therapy. Four weeks later, both ulcers received daily topical timolol. Three months later, the test ulcer was completely epithelized and remains healed for over 15 months. However, the control showed minimal signs of improvement. In companion studies in our laboratory, human AMSC were cultured in Minimum Essential Medium Eagle Alpha Modifications (MEMα) with fetal bovine serum (FBS). Timolol was administered to AMSC prior to treatment with epinephrine and 104 bacteria/ml heat-killed Staphylococcus aureus. The MEMα with FBS devoid of AMSC served as a background control. After 24 h, cell culture supernatants and protein lysates were collected to determine cytokine production. There was a statistical significant decrease in pro-inflammatory interleukin-6 and -8 induced by the bacteria (to model the wound environment) in AMSC in the presence of timolol compared with control (p < 0.5). This is the first case of a successful combination of autologous AMSC-enriched, HDL with topical timolol for the healing of chronic venous leg ulcers.

Original languageEnglish (US)
Pages (from-to)186-190
Number of pages5
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2018

Keywords

  • autologous adipose mesenchymal stem cell
  • high-density lipoaspirate
  • timolol
  • venous leg ulcer
  • wound healing

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

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