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Characterization of a Murine Pressure Ulcer Model to Assess Efficacy of Adipose-derived Stromal Cells.

Strong AL, Bowles AC, MacCrimmon CP, Lee SJ, Frazier TP, Katz AJ, Gawronska-Kozak B, Bunnell BA, Gimble JM - Plast Reconstr Surg Glob Open (2015)

Bottom Line: Optimal results were obtained with the 2-cycle model based on the wound size, histology, and gene expression profile of representative angiogenic and reparative messenger RNAs.When treated with adipose-derived stromal/stem cells, pressure ulcer wounds displayed a dose-dependent and significant acceleration in wound closure rates and improved tissue histology.These findings document the utility of this simplified preclinical model for the evaluation of novel tissue engineering and medical approaches to treat pressure ulcers in humans.

View Article: PubMed Central - PubMed

Affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, La.; Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Florida, Gainesville, Fla.; Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Olsztyn, Poland; Department of Pharmacology, Tulane University School of Medicine, New Orleans, La.; LaCell LLC, New Orleans, La.; Department of Medicine, Tulane Health Sciences Center, New Orleans, La.; and Department of Surgery, Tulane Health Sciences Center, New Orleans, La.

ABSTRACT

Background: As the world's population lives longer, the number of individuals at risk for pressure ulcers will increase considerably in the coming decades. In developed countries, up to 18% of nursing home residents suffer from pressure ulcers and the resulting hospital costs can account for up to 4% of a nation's health care budget. Although full-thickness surgical skin wounds have been used as a model, preclinical rodent studies have demonstrated that repeated cycles of ischemia and reperfusion created by exposure to magnets most closely mimic the human pressure ulcer condition.

Methods: This study uses in vivo and in vitro quantitative parameters to characterize the temporal kinetics and histology of pressure ulcers in young, female C57BL/6 mice exposed to 2 or 3 ischemia-reperfusion cycles. This pressure ulcer model was validated further in studies examining the efficacy of adipose-derived stromal/stem cell administration.

Results: Optimal results were obtained with the 2-cycle model based on the wound size, histology, and gene expression profile of representative angiogenic and reparative messenger RNAs. When treated with adipose-derived stromal/stem cells, pressure ulcer wounds displayed a dose-dependent and significant acceleration in wound closure rates and improved tissue histology.

Conclusion: These findings document the utility of this simplified preclinical model for the evaluation of novel tissue engineering and medical approaches to treat pressure ulcers in humans.

No MeSH data available.


Related in: MedlinePlus

Two IR cycles result in delayed wound closure. Wounds were induced on the dorsal skin of mice by applying 2 or 3 IR cycles. Daily digital caliper measurements of the length and width of the wounds were acquired, and wound size was calculated. Wound closure was determined by soaking cotton swabs in 3% hydrogen peroxide and applied to wounds. The appearance of bubbles was recorded, and the total percentage of wounds open is shown. Mean ± standard error of the mean. *P < 0.05; #P < 0.01.
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Figure 2: Two IR cycles result in delayed wound closure. Wounds were induced on the dorsal skin of mice by applying 2 or 3 IR cycles. Daily digital caliper measurements of the length and width of the wounds were acquired, and wound size was calculated. Wound closure was determined by soaking cotton swabs in 3% hydrogen peroxide and applied to wounds. The appearance of bubbles was recorded, and the total percentage of wounds open is shown. Mean ± standard error of the mean. *P < 0.05; #P < 0.01.

Mentions: Quantification of wound size with digital calipers accurately correlated with qualitative analysis of skin by digital imaging. Skin subjected to 3 IR cycles underwent significant healing 2 days post defect induction (PDI) from 98.5 to 85.5 mm2 and continued to heal faster than skin subjected to 2 IR cycles. After 5 days PDI, skin subjected to 3 IR cycles was significantly smaller (75.2 mm2) than skin subjected to 2 IR cycles (92.5 mm2; P < 0.01; Fig. 2). Following 10 days PDI, skin subjected to 2 and 3 IR cycles was 46.3 mm2 and 24.1 mm2, respectively (Fig. 2). There was no significant difference in wound size between 2 and 3 IR cycles after 15 days PDI. H2O2 testing for reepithelialization showed earlier formation and resolution of open wounds following 3 IR cycles compared with 2 IR cycles (Fig. 2).


Characterization of a Murine Pressure Ulcer Model to Assess Efficacy of Adipose-derived Stromal Cells.

Strong AL, Bowles AC, MacCrimmon CP, Lee SJ, Frazier TP, Katz AJ, Gawronska-Kozak B, Bunnell BA, Gimble JM - Plast Reconstr Surg Glob Open (2015)

Two IR cycles result in delayed wound closure. Wounds were induced on the dorsal skin of mice by applying 2 or 3 IR cycles. Daily digital caliper measurements of the length and width of the wounds were acquired, and wound size was calculated. Wound closure was determined by soaking cotton swabs in 3% hydrogen peroxide and applied to wounds. The appearance of bubbles was recorded, and the total percentage of wounds open is shown. Mean ± standard error of the mean. *P < 0.05; #P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4387156&req=5

Figure 2: Two IR cycles result in delayed wound closure. Wounds were induced on the dorsal skin of mice by applying 2 or 3 IR cycles. Daily digital caliper measurements of the length and width of the wounds were acquired, and wound size was calculated. Wound closure was determined by soaking cotton swabs in 3% hydrogen peroxide and applied to wounds. The appearance of bubbles was recorded, and the total percentage of wounds open is shown. Mean ± standard error of the mean. *P < 0.05; #P < 0.01.
Mentions: Quantification of wound size with digital calipers accurately correlated with qualitative analysis of skin by digital imaging. Skin subjected to 3 IR cycles underwent significant healing 2 days post defect induction (PDI) from 98.5 to 85.5 mm2 and continued to heal faster than skin subjected to 2 IR cycles. After 5 days PDI, skin subjected to 3 IR cycles was significantly smaller (75.2 mm2) than skin subjected to 2 IR cycles (92.5 mm2; P < 0.01; Fig. 2). Following 10 days PDI, skin subjected to 2 and 3 IR cycles was 46.3 mm2 and 24.1 mm2, respectively (Fig. 2). There was no significant difference in wound size between 2 and 3 IR cycles after 15 days PDI. H2O2 testing for reepithelialization showed earlier formation and resolution of open wounds following 3 IR cycles compared with 2 IR cycles (Fig. 2).

Bottom Line: Optimal results were obtained with the 2-cycle model based on the wound size, histology, and gene expression profile of representative angiogenic and reparative messenger RNAs.When treated with adipose-derived stromal/stem cells, pressure ulcer wounds displayed a dose-dependent and significant acceleration in wound closure rates and improved tissue histology.These findings document the utility of this simplified preclinical model for the evaluation of novel tissue engineering and medical approaches to treat pressure ulcers in humans.

View Article: PubMed Central - PubMed

Affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, La.; Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Florida, Gainesville, Fla.; Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Olsztyn, Poland; Department of Pharmacology, Tulane University School of Medicine, New Orleans, La.; LaCell LLC, New Orleans, La.; Department of Medicine, Tulane Health Sciences Center, New Orleans, La.; and Department of Surgery, Tulane Health Sciences Center, New Orleans, La.

ABSTRACT

Background: As the world's population lives longer, the number of individuals at risk for pressure ulcers will increase considerably in the coming decades. In developed countries, up to 18% of nursing home residents suffer from pressure ulcers and the resulting hospital costs can account for up to 4% of a nation's health care budget. Although full-thickness surgical skin wounds have been used as a model, preclinical rodent studies have demonstrated that repeated cycles of ischemia and reperfusion created by exposure to magnets most closely mimic the human pressure ulcer condition.

Methods: This study uses in vivo and in vitro quantitative parameters to characterize the temporal kinetics and histology of pressure ulcers in young, female C57BL/6 mice exposed to 2 or 3 ischemia-reperfusion cycles. This pressure ulcer model was validated further in studies examining the efficacy of adipose-derived stromal/stem cell administration.

Results: Optimal results were obtained with the 2-cycle model based on the wound size, histology, and gene expression profile of representative angiogenic and reparative messenger RNAs. When treated with adipose-derived stromal/stem cells, pressure ulcer wounds displayed a dose-dependent and significant acceleration in wound closure rates and improved tissue histology.

Conclusion: These findings document the utility of this simplified preclinical model for the evaluation of novel tissue engineering and medical approaches to treat pressure ulcers in humans.

No MeSH data available.


Related in: MedlinePlus