title: Adipose-Derived Regenerative Cell Therapy for Burn Wound Healing: A Comparison of Two Delivery Methods.
abstract: Objective:The use of noncultured autologous stromal vascular fraction or clinical grade adipose-derived regenerative cells (ADRCs) is a promising strategy to promote wound healing and tissue repair. Nevertheless, issues regarding the optimal mode of administration remain unclear. The purpose of this study was to compare the effects of local injection and topical spray delivery of ADRCs in a porcine model of thermal burns.Approach:Full-thickness thermal burns were created on the dorsum of 10 Gottingen minipigs. Two days following injury, wounds underwent fascial excision and were randomized to receive control vehicle or freshly isolated autologous ADRCs delivered by either multiple injections into or surrounding the wound bed, or by spray onto the wound surface (0.25 × 106viable cells/cm2). Healing was evaluated by planimetry, histopathology, and immunohistochemistry at day 7, 12, 16, 21, and 28 posttreatment.Results:In vitroanalysis demonstrated that there was no substantial loss of cell number or viability attributable to the spray procedure. Planimetric assessment revealed that delivery of ADRCs by either local injection or topical spray increased wound reepithelialization relative to control at day 14. No significant difference in wound reepithelialization was observed between both delivery approaches. In addition, on day 7 posttreatment, blood vessel density was greater in wounds receiving local or topical spray ADRCs than in the wounds treated with vehicle control. Histopathologic analysis suggests that ADRC treatment may modulate the inflammatory response by reducing neutrophil infiltration at day 7 and 12 posttreatment, irrespective of the route of administration.Conclusions:These data demonstrate that local injection and spray delivery of ADRCs modulate inflammation and improve wound angiogenesis and epithelialization. Importantly, both delivery routes exhibited similar effects on wound healing. Given the greater ease-of-use associated with topical spray delivery, these data support the use of a spray system for autologous ADRC delivery.
authors.affiliation: Cytori Therapeutics, Inc. , San Diego, California.
authors.forename: Philippe
authors.initials: P
authors.lastname: Foubert
authors.affiliation: Cytori Therapeutics, Inc. , San Diego, California.
authors.forename: Andreina D
authors.initials: AD
authors.lastname: Gonzalez
authors.affiliation: Cytori Therapeutics, Inc. , San Diego, California.
authors.forename: Stephan
authors.initials: S
authors.lastname: Teodosescu
authors.affiliation: Lovelace Respiratory Research Institute , Albuquerque, New Mexico.
authors.forename: Felipe
authors.initials: F
authors.lastname: Berard
authors.affiliation: Lovelace Respiratory Research Institute , Albuquerque, New Mexico.
authors.forename: Melanie
authors.initials: M
authors.lastname: Doyle-Eisele
authors.affiliation: Department of Pathology, Toxikon Corporation , Bedford, Massachusetts.
authors.forename: Krishna
authors.initials: K
authors.lastname: Yekkala
authors.affiliation: UCSD Medical Center, University of California , San Diego, California.
authors.forename: Mayer
authors.initials: M
authors.lastname: Tenenhaus
authors.affiliation: Cytori Therapeutics, Inc. , San Diego, California.
authors.forename: John K
authors.initials: JK
authors.lastname: Fraser