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Effect of Immunocompromising Therapy on In Vivo Cell Survival in Musculoskeletal Tissue Engineering

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Abstract

Replacing soft tissue after trauma or tumor surgery remains a major challenge in reconstructive surgery. A promising alternative is the possibility of using bioartificial musculoskeletal tissue created out of primary muscle cells. However, poor survival of transplanted cells and suboptimal matrix qualities limit the development of bioartificial tissues (BATs). Furthermore, granulocyte infiltration into BATs also appears to impair cell survival. Therefore, this study investigates how immunocompromising therapy affects the survival of transplanted myoblasts in a three-dimensional vascularized BAT. Myoblasts (4 × 106) were transfected with a luciferase-reporter sequence and then transplanted into an in vivo bioreactor placed within the abdominal wall of Wistar rats. Bioluminescence was used to monitor the myoblasts in vivo. The rats were either not treated (group 1, control) or subjected to immunocompromising therapy that involved daily administration of cyclosporine A (group 2), prednisolone (group 3), or both (group 4). Bioluminescence monitoring showed that luminescence signals on day 7 were significantly higher in all immunocompromised animals than those in the animals in the control group (group 2: p < 0.0001; group 3: p = 0.0073; group 4: p = 0.0053). Moreover, TUNEL analysis revealed that the apoptosis rate was significantly lower in the cyclosporine-A-treated group than that in the control group (p = 0.037). Our results indicate that cyclosporine A and prednisolone enhance the in vivo survival of transplanted myoblasts and thus they can be considered as a supportive medical treatment for increasing cell survival after cell transplantation in tissue engineering.

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Acknowledgments

The psPAX2 and pMD2.G plasmids were kindly provided by Didier Trono (LVG-Trono Lab, Lausanne, Switzerland), and the lentiviral vector pEMW-Luc was provided by Gan Shu Uin (Department of Surgery, NUS, Singapore). We thank Andrea Fritz and Martina Tappe for technical assistance and tissue embedding, processing, and staining.

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Authors and Affiliations

  1. Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Center, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany

    Sebastian E. Dunda, Laura K. Krings, Markus F. Ranker, Sabien G. van Neerven, Ahmet Bozkurt & Norbert Pallua

  2. Department of Anatomy, RWTH University Hospital, 52074, Aachen, Germany

    Christoph Wruck

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  1. Sebastian E. Dunda
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  2. Laura K. Krings
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Correspondence to Sebastian E. Dunda.

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Dunda, S.E., Krings, L.K., Ranker, M.F. et al. Effect of Immunocompromising Therapy on In Vivo Cell Survival in Musculoskeletal Tissue Engineering. J. Med. Biol. Eng. 35, 134–141 (2015). https://doi.org/10.1007/s40846-015-0017-8

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  • DOI: https://doi.org/10.1007/s40846-015-0017-8

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