Porcine heterotopic composite tissue allograft transplantation using a large animal model for preclinical studies

Yur Ren Kuo, Justin Michael Sacks, W P Andrew Lee, Wen Sheng Wu, Nai Siong Kueh, Sheng Fa Yao, Yuan Cheng Chiang

Research output: Contribution to journalArticle

Abstract

Background: Composite tissue allograft (CTA) transplantation is currently limited by the risks of side effects resulting from long-term high-dose immunosuppression. Therefore, preclinical animal models are essential to help CTA transplantation advance into clinical reality. Evidence has shown that small-animal model (rodents) immunotherapy protocols cannot be directly applied to humans. This study investigated whether a miniature porcine model is reproducible for preclinical studies. Methods: Based on the concept of vascularized skeletal tissue allograft transplantation, limb heterotopic allograft tissue from a mismatched donor miniature pig consisting of the distal femur, knee joint, tibia, fibula, and surrounding muscle with a vascularized skin paddle model supplied by the superficial femoral vessels was transplanted into recipient pigs. Swine viability and rejection signs of the allograft were monitored postoperatively. Histopathological changes in the allograft tissues were examined using hematoxylin and eosin staining if the allo-skin flap was rejected. Results: The recipient pigs were ambulatory immediately following surgery. The flaps showed no visible signs of rejection over the first 4 days of observation. The skin flaps appeared bluish-purple and edematous on postoperative days 5-7, and progressed to tissue necrosis and rejection on postoperative days 8-13. Histological examination revealed marked mononuclear cell infiltration and necrotic changes in the all rejected tissues, especial in the allograft skin tissues (skin > muscle > bone > cartilage). Conclusions: The results showed this the porcine CTA model is reproducible and suitable for preclinical training for human CTA transplantation. Monitoring of the allo-skin flap is a useful strategy to evaluate composite tissue allograft rejection.

Original languageEnglish (US)
Pages (from-to)268-274
Number of pages7
JournalChang Gung Medical Journal
Volume29
Issue number3
StatePublished - May 2006
Externally publishedYes

Fingerprint

Composite Tissue Allografts
Tissue Transplantation
Choristoma
Swine
Animal Models
Allografts
Skin
Miniature Swine
Muscles
Fibula
Hematoxylin
Eosine Yellowish-(YS)
Knee Joint
Thigh
Tibia
Femur
Immunotherapy
Immunosuppression
Cartilage
Rodentia

Keywords

  • Composite tissue allograft
  • Heterotopic
  • Transplantation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kuo, Y. R., Sacks, J. M., Lee, W. P. A., Wu, W. S., Kueh, N. S., Yao, S. F., & Chiang, Y. C. (2006). Porcine heterotopic composite tissue allograft transplantation using a large animal model for preclinical studies. Chang Gung Medical Journal, 29(3), 268-274.

Porcine heterotopic composite tissue allograft transplantation using a large animal model for preclinical studies. / Kuo, Yur Ren; Sacks, Justin Michael; Lee, W P Andrew; Wu, Wen Sheng; Kueh, Nai Siong; Yao, Sheng Fa; Chiang, Yuan Cheng.

In: Chang Gung Medical Journal, Vol. 29, No. 3, 05.2006, p. 268-274.

Research output: Contribution to journalArticle

Kuo, Yur Ren ; Sacks, Justin Michael ; Lee, W P Andrew ; Wu, Wen Sheng ; Kueh, Nai Siong ; Yao, Sheng Fa ; Chiang, Yuan Cheng. / Porcine heterotopic composite tissue allograft transplantation using a large animal model for preclinical studies. In: Chang Gung Medical Journal. 2006 ; Vol. 29, No. 3. pp. 268-274.
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