Development of a porcine delayed wound-healing model and its use in testing a novel cell-based therapy

Ivan Hadad, Brian H. Johnstone, Jeffrey G. Brabham, Matthew W. Blanton, Pamela I. Rogers, Cory Fellers, James L. Solomon, Stephanie Merfeld-Clauss, Colleen DesRosiers, Joseph Dynlacht, John J. Coleman, Keith L. March

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Purpose: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. Methods and Materials: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm2 wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. Results: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. Conclusions: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

Original languageEnglish
Pages (from-to)888-896
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume78
Issue number3
DOIs
StatePublished - 2010

Fingerprint

wound healing
stem cells
Cell- and Tissue-Based Therapy
Wound Healing
therapy
Platelet-Rich Plasma
Swine
Stem Cells
platelets
cells
Sodium Chloride
healing
fibrin
Skin
Radiation
Fibrin
Wounds and Injuries
Gels
gels
swine

Keywords

  • Adult stem cells
  • Disease models
  • Radiation injuries
  • Wound healing

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research
  • Medicine(all)

Cite this

Development of a porcine delayed wound-healing model and its use in testing a novel cell-based therapy. / Hadad, Ivan; Johnstone, Brian H.; Brabham, Jeffrey G.; Blanton, Matthew W.; Rogers, Pamela I.; Fellers, Cory; Solomon, James L.; Merfeld-Clauss, Stephanie; DesRosiers, Colleen; Dynlacht, Joseph; Coleman, John J.; March, Keith L.

In: International Journal of Radiation Oncology Biology Physics, Vol. 78, No. 3, 2010, p. 888-896.

Research output: Contribution to journalArticle

Hadad, I, Johnstone, BH, Brabham, JG, Blanton, MW, Rogers, PI, Fellers, C, Solomon, JL, Merfeld-Clauss, S, DesRosiers, C, Dynlacht, J, Coleman, JJ & March, KL 2010, 'Development of a porcine delayed wound-healing model and its use in testing a novel cell-based therapy', International Journal of Radiation Oncology Biology Physics, vol. 78, no. 3, pp. 888-896. https://doi.org/10.1016/j.ijrobp.2010.05.002
Hadad, Ivan ; Johnstone, Brian H. ; Brabham, Jeffrey G. ; Blanton, Matthew W. ; Rogers, Pamela I. ; Fellers, Cory ; Solomon, James L. ; Merfeld-Clauss, Stephanie ; DesRosiers, Colleen ; Dynlacht, Joseph ; Coleman, John J. ; March, Keith L. / Development of a porcine delayed wound-healing model and its use in testing a novel cell-based therapy. In: International Journal of Radiation Oncology Biology Physics. 2010 ; Vol. 78, No. 3. pp. 888-896.
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abstract = "Purpose: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. Methods and Materials: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm2 wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. Results: The single radiation dose produced a significant loss of dermal microvasculature density (75{\%}) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2{\%} improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. Conclusions: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.",
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AU - Rogers, Pamela I.

AU - Fellers, Cory

AU - Solomon, James L.

AU - Merfeld-Clauss, Stephanie

AU - DesRosiers, Colleen

AU - Dynlacht, Joseph

AU - Coleman, John J.

AU - March, Keith L.

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N2 - Purpose: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. Methods and Materials: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm2 wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. Results: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. Conclusions: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

AB - Purpose: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. Methods and Materials: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm2 wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. Results: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. Conclusions: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

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