title: Human adipose-derived stromal cells accelerate diabetic wound healing: impact of cell formulation and delivery.
abstract: Human adipose-derived stromal cells (ASCs) have been shown to possess therapeutic potential in a variety of settings, including cutaneous wound healing; however, it is unknown whether the regenerative properties of this cell type can be applied to diabetic ulcers. ASCs collected from elective surgical procedures were used to treat full-thickness dermal wounds in leptin receptor-deficient (db/db) mice. Cells were delivered either as multicellular aggregates or as cell suspensions to determine the impact of cell formulation and delivery methods on biological activity and in vivo therapeutic effect. After treatment with ASCs that were formulated as multicellular aggregates, diabetic wounds experienced a significant increase in the rate of wound closure compared to wounds treated with an equal number of ASCs delivered in suspension. Analysis of culture supernatant and gene arrays indicated that ASCs formulated as three-dimensional aggregates produce significantly more extracellular matrix proteins (e.g., tenascin C, collagen VI alpha3, and fibronectin) and secreted soluble factors (e.g., hepatocyte growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-14) compared to monolayer culture. From these results, it is clear that cell culture, formulation, and delivery method have a large impact on the in vitro and in vivo biology of ASCs.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Amos
authors.forename: Sahil K
authors.initials: SK
authors.lastname: Kapur
authors.forename: Peter C
authors.initials: PC
authors.lastname: Stapor
authors.forename: Hulan
authors.initials: H
authors.lastname: Shang
authors.forename: Stefan
authors.initials: S
authors.lastname: Bekiranov
authors.forename: Moshe
authors.initials: M
authors.lastname: Khurgel
authors.forename: George T
authors.initials: GT
authors.lastname: Rodeheaver
authors.forename: Shayn M
authors.initials: SM
authors.lastname: Peirce
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Katz
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002449:Cell Aggregation; D018929:Cell Culture Techniques; D003920:Diabetes Mellitus / Q000473:pathology*; D016503:Drug Delivery Systems / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D013997:Time Factors; D014945:Wound Healing
chemical_list: D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger