Ozan Luay Abbas1, Orhan Özatik1, Zeynep Burçin Gönen1, Atacan Emre Koçman1, Ilknur Dağ1, Fikriye Yasemin Özatik1, Dilek Bahar1, Ahmet Musmul1. 1. From the Faculty of Medicine, Department of Plastic, Reconstructive, and Aesthetic Surgery, Ahi Evran University; the Faculty of Medicine, Department of Histology and Embryology, Dumlupinar University; Gen Kök Genome and Stem Cell Center, Erciyes University; the Faculty of Medicine, Department of Plastic, Reconstructive, and Aesthetic Surgery, the Central Research Laboratory Research and Application Center, and the Faculty of Medicine, Department of Biostatistics, Osmangazi University; and the Faculty of Medicine, Department of Pharmacology, Dumlupinar University.
Abstract
BACKGROUND: Successful limb replantation must be based not only on the viability of the amputated part but also on satisfactory long-term functional recovery. Once the vascular, skeletal, and soft-tissue problems have been taken care of, nerve recovery becomes the ultimate limiting factor. Unfortunately, nerve regeneration after limb replantation is impaired by several consequences. The authors tested the hypothesis that bone marrow mesenchymal stem cells could improve nerve regeneration outcomes in an experimental model of limb replantation. METHODS: Twenty rats underwent replantation after total hindlimb amputation. Animals were subdivided into two groups: a replanted but nontreated control group and a replanted and bone marrow mesenchymal stem cell-transplanted group. Three months after surgery, nerve regeneration was assessed using functional, electrophysiologic, histomorphologic, and immunohistochemical analyses. RESULTS: Bone marrow mesenchymal stem cell-treated animals showed significantly better sciatic functional index levels and higher compound muscle action potential amplitudes in comparison with the controls. Histomorphometric analysis revealed that the number of regenerating axons was approximately two-fold greater in the treated nerves. In addition, the mean g-ratio of these axons was within the optimal range. Immunohistochemical assessment revealed that expression of S-100 and myelin basic protein in the treated nerves was significantly higher than in controls. Correspondingly, the expression levels of anti-protein gene product 9.5 and vesicular acetylcholine transporter in motor endplates were also significantly higher. Finally, muscles in the bone marrow mesenchymal stem cell-transplanted group showed significantly larger average fiber areas. CONCLUSION: The authors' findings demonstrate that it is possible to improve the degree of nerve regeneration after limb replantation by bone marrow mesenchymal stem cell transplantation.
BACKGROUND: Successful limb replantation must be based not only on the viability of the amputated part but also on satisfactory long-term functional recovery. Once the vascular, skeletal, and soft-tissue problems have been taken care of, nerve recovery becomes the ultimate limiting factor. Unfortunately, nerve regeneration after limb replantation is impaired by several consequences. The authors tested the hypothesis that bone marrow mesenchymal stem cells could improve nerve regeneration outcomes in an experimental model of limb replantation. METHODS: Twenty rats underwent replantation after total hindlimb amputation. Animals were subdivided into two groups: a replanted but nontreated control group and a replanted and bone marrow mesenchymal stem cell-transplanted group. Three months after surgery, nerve regeneration was assessed using functional, electrophysiologic, histomorphologic, and immunohistochemical analyses. RESULTS: Bone marrow mesenchymal stem cell-treated animals showed significantly better sciatic functional index levels and higher compound muscle action potential amplitudes in comparison with the controls. Histomorphometric analysis revealed that the number of regenerating axons was approximately two-fold greater in the treated nerves. In addition, the mean g-ratio of these axons was within the optimal range. Immunohistochemical assessment revealed that expression of S-100 and myelin basic protein in the treated nerves was significantly higher than in controls. Correspondingly, the expression levels of anti-protein gene product 9.5 and vesicular acetylcholine transporter in motor endplates were also significantly higher. Finally, muscles in the bone marrow mesenchymal stem cell-transplanted group showed significantly larger average fiber areas. CONCLUSION: The authors' findings demonstrate that it is possible to improve the degree of nerve regeneration after limb replantation by bone marrow mesenchymal stem cell transplantation.
Authors: Elisabeth Simader; Lucian Beer; Maria Laggner; Vera Vorstandlechner; Alfred Gugerell; Michael Erb; Polina Kalinina; Dragan Copic; Doris Moser; Andreas Spittler; Erwin Tschachler; Hendrik Jan Ankersmit; Michael Mildner Journal: Cell Death Dis Date: 2019-09-30 Impact factor: 8.469