title: Combination therapy of autologous adipose mesenchymal stem cell-enriched, high-density lipoaspirate and topical timolol for healing chronic wounds.
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. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA, USA.
authors.forename: Larissa
authors.initials: L
authors.lastname: Larsen
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA, USA.|Department of Dermatology, Veterans Administration, Northern California Health Care System, Mather, CA, USA.
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Tchanque-Fossuo
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA, USA.
authors.forename: Farzam
authors.initials: F
authors.lastname: Gorouhi
authors.affiliation: Department of Plastic Surgery, University of California, Davis, Sacramento, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Boudreault
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA, USA.
authors.forename: Chuong
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Department of Biological Sciences, California State University, Sacramento, CA, USA.
authors.forename: Jaime J
authors.initials: JJ
authors.lastname: Fuentes
authors.affiliation: Department of Biological Sciences, California State University, Sacramento, CA, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Crawford
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA, USA.|Department of Surgery, Podiatry Section, Veterans Administration, Northern California Health Care System, Mather, CA, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Dahle
authors.affiliation: Department of Plastic Surgery, University of California, Davis, Sacramento, CA, USA.|Plastic Surgery, Veterans Administration, Northern California Health Care System, Mather, CA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Whetzel
authors.affiliation: Department of Dermatology, University of California, Davis, Sacramento, CA, USA.|Department of Dermatology, Veterans Administration, Northern California Health Care System, Mather, CA, USA.
authors.forename: R Rivkah
authors.initials: RR
authors.lastname: Isseroff
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D013999:Timolol / Q000494:pharmacology* / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014647:Varicose Ulcer / Q000473:pathology / Q000628:therapy; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D013999:Timolol
keywords: autologous adipose mesenchymal stem cell; high-density lipoaspirate; timolol; venous leg ulcer; wound healing