Orthotopic Transplantation of Achilles Tendon Allograft in Rats: With or without Incorporation of Autologous Mesenchymal Stem Cells

Michael Aynardi, Talal Zahoor, Reed Mitchell, Jeffrey Loube, Tyler Feltham, Lumanti Manandhar, Sharada Paudel, Lew Schon, Zijun Zhang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at −80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully appreciate the functional benefits of MSCs.

Original languageEnglish (US)
Pages (from-to)245-255
Number of pages11
JournalCell Transplantation
Volume27
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

Achilles Tendon
Tendons
Stem cells
Mesenchymal Stromal Cells
Allografts
Rats
Transplantation
Animals
Extremities
Gait
Tissue
Histology
Growth Differentiation Factor 5
Cell Tracking
Collagen
Surgery
Calcaneus
Muscle
Collagen Type III
Subcutaneous Fat

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

Cite this

Aynardi, Michael ; Zahoor, Talal ; Mitchell, Reed ; Loube, Jeffrey ; Feltham, Tyler ; Manandhar, Lumanti ; Paudel, Sharada ; Schon, Lew ; Zhang, Zijun. / Orthotopic Transplantation of Achilles Tendon Allograft in Rats : With or without Incorporation of Autologous Mesenchymal Stem Cells. In: Cell Transplantation. 2018 ; Vol. 27, No. 2. pp. 245-255.
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abstract = "The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at −80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully appreciate the functional benefits of MSCs.",
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Aynardi, M, Zahoor, T, Mitchell, R, Loube, J, Feltham, T, Manandhar, L, Paudel, S, Schon, L & Zhang, Z 2018, 'Orthotopic Transplantation of Achilles Tendon Allograft in Rats: With or without Incorporation of Autologous Mesenchymal Stem Cells', Cell Transplantation, vol. 27, no. 2, pp. 245-255. https://doi.org/10.1177/0963689717745891

Orthotopic Transplantation of Achilles Tendon Allograft in Rats : With or without Incorporation of Autologous Mesenchymal Stem Cells. / Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun.

In: Cell Transplantation, Vol. 27, No. 2, 01.02.2018, p. 245-255.

Research output: Contribution to journalArticle

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AU - Loube, Jeffrey

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AU - Schon, Lew

AU - Zhang, Zijun

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