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Combination therapy of autologous adipose mesenchymal stem cell‐enriched, high‐density lipoaspirate and topical timolol for healing chronic wounds
Author(s) -
Larsen Larissa,
TchanqueFossuo Catherine N.,
Gorouhi Farzam,
Boudreault David,
Nguyen Chuong,
Fuentes Jaime J.,
Crawford Robert W.,
Dahle Sara E.,
Whetzel Thomas,
Isseroff R. Rivkah
Publication year - 2018
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.2390
Subject(s) - medicine , timolol , wound healing , venous leg ulcer , mesenchymal stem cell , surgery , adipose tissue , anesthesia , pathology , intraocular pressure
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.