De novo generation of permanent neovascularized soft tissue appendages by platelet-derived growth factor

Roger K. Khouri, Sung Pyo Hong, E Gene Deune, John E. Tarpley, Suk Zu Song, Cuneyt M. Serdar, Glenn F. Pierce

Research output: Contribution to journalArticle

Abstract

Treatment of wounds with pharmacologic doses of the BB homodimeric form of recombinant PDGF (rPDGF-BB) induces the recruitment, activation, and proliferation of mesenchymal cells, resulting in the deposition of provisional, and subsequently collagen-containing extracellular matrix. In preliminary experiments with an in vitro growth chamber model in the rat consisting of a silicone shell containing a dissected femoral vascular bundle, we found that rPDGF-BB incorporated into a rapidly dissolving collage type I film induces the generation of a marked, but transient amount of de novo tissue around the femoral vascular bundle. In the present studies, the new tissue generated around the femoral vascular bundle was wrapped with a full thickness syngeneic skin graft to determine if functional support of the graft would lead to sustained maintenance of the underlying generated tissue and create an epithelialized soft tissue appendage. The tissue generated after a single application of rPDGF-BB was skin grafted on the 10th day, exteriorized 20 d later, and observed for an additional month. This led to the formation of soft tissue appendages which demonstrated marked neovascularization, fibroblast migration and proliferation, and increased glycosaminoglycan, fibronectin, and collagen fibril deposition, now leading to preservation of the newly generated tissue. In contrast, minimal new tissue was generated in control-treated vascular bundles or bundles treated with inactive PDGF-BB, and grafting with skin failed to sustain the underlying tissue. Thus, rPDGF-BB coupled with skin grafting induced the formation of functional large soft tissue appendages which are potentially useful clinically to fill tissue defects or to serve as a cell delivery system for transfected genes.

Original languageEnglish (US)
Pages (from-to)1757-1763
Number of pages7
JournalJournal of Clinical Investigation
Volume94
Issue number5
StatePublished - Nov 1994
Externally publishedYes

Fingerprint

Platelet-Derived Growth Factor
Blood Vessels
Thigh
Skin Transplantation
Collagen
Transplants
Gene Transfer Techniques
Skin
Silicones
Glycosaminoglycans
Fibronectins
Extracellular Matrix
platelet-derived growth factor BB
Fibroblasts
Maintenance
Cell Proliferation

Keywords

  • angiogenesis
  • cell proliferation
  • extracellular matrix
  • fibroblasts
  • gene therapy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Khouri, R. K., Hong, S. P., Deune, E. G., Tarpley, J. E., Song, S. Z., Serdar, C. M., & Pierce, G. F. (1994). De novo generation of permanent neovascularized soft tissue appendages by platelet-derived growth factor. Journal of Clinical Investigation, 94(5), 1757-1763.

De novo generation of permanent neovascularized soft tissue appendages by platelet-derived growth factor. / Khouri, Roger K.; Hong, Sung Pyo; Deune, E Gene; Tarpley, John E.; Song, Suk Zu; Serdar, Cuneyt M.; Pierce, Glenn F.

In: Journal of Clinical Investigation, Vol. 94, No. 5, 11.1994, p. 1757-1763.

Research output: Contribution to journalArticle

Khouri, RK, Hong, SP, Deune, EG, Tarpley, JE, Song, SZ, Serdar, CM & Pierce, GF 1994, 'De novo generation of permanent neovascularized soft tissue appendages by platelet-derived growth factor', Journal of Clinical Investigation, vol. 94, no. 5, pp. 1757-1763.
Khouri, Roger K. ; Hong, Sung Pyo ; Deune, E Gene ; Tarpley, John E. ; Song, Suk Zu ; Serdar, Cuneyt M. ; Pierce, Glenn F. / De novo generation of permanent neovascularized soft tissue appendages by platelet-derived growth factor. In: Journal of Clinical Investigation. 1994 ; Vol. 94, No. 5. pp. 1757-1763.
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