TY - JOUR
T1 - Microcomputed analysis of nerve angioarchitecture after combined stem cell delivery and surgical angiogenesis to nerve allograft
AU - Saffari, T. M.
AU - Mathot, F.
AU - Thaler, R.
AU - van Wijnen, A. J.
AU - Bishop, A. T.
AU - Shin, A. Y.
N1 - Funding Information:
“Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number R01 NS102360. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”
Funding Information:
The authors would like to thank Jim Postier (Rochester, MN) for the artwork of Figure 1 and Andrew J. Vercnocke for his help with the ERODE/DILATE program. This work was supported in part by the Mayo Clinic X-ray Imaging Core.
Funding Information:
The authors would like to thank Jim Postier (Rochester, MN) for the artwork of Figure 1 and Andrew J. Vercnocke for his help with the ERODE/DILATE program. This work was supported in part by the Mayo Clinic X-ray Imaging Core. NIH grant No.: R01NS102360. Mayo Clinic Institutional Animal Care and Use Committee (IACUC A3348-18). Tiam Mana Saffari: contributed to the conception, execution of the experiments, collection, analysis and interpretation of the data and drafting the manuscript for submission. Femke Mathot: contributed to the conception, interpretation of the data, and drafting the manuscript for submission. Roman Thaler: contributed to the execution of experiments as well as editing the manuscript. Andre J. van Wijnen: contributed to the interpretation of data as well as editing the manuscript. Allen T. Bishop: contributed to the interpretation of data as well as editing the manuscript. Alexander Y. Shin: contributed to the conception and interpretation of data, the acquisition of funding, and editing the manuscript. ?Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number R01 NS102360. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.?
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/8
Y1 - 2021/8
N2 - Introduction: A detailed three-dimensional (3D) evaluation of microvasculature is evolving to be a powerful tool, providing mechanistic understanding of angiomodulating strategies. The aim of this study was to evaluate the microvascular architecture of nerve allografts after combined stem cell delivery and surgical angiogenesis in a rat sciatic nerve defect model. Materials and Methods: In 25 Lewis rats, sciatic nerve gaps were repaired with (i) autografts, (ii) allografts, (iii) allografts wrapped in a pedicled superficial inferior epigastric artery fascia (SIEF) flap to provide surgical angiogenesis, combined with (iv) undifferentiated mesenchymal stem cells (MSC) and (v) MSCs differentiated into Schwann cell-like cells. At two weeks, vascular volume was measured using microcomputed tomography, and percentage and volume of vessels at different diameters were evaluated and compared with controls. Results: The vascular volume was significantly greatest in allografts treated with undifferentiated MSCs and surgical angiogenesis combined as compared to all experimental groups (P<0.01 as compared to autografts, P<0.0001 to allografts, and P<0.05 to SIEF and SIEF combined with differentiated MSCs, respectively). Volume and diameters of vessel segments in nerve allografts were enhanced by surgical angiogenesis. These distributions were further improved when surgical angiogenesis was combined with stem cells, with greatest increase found when combined with undifferentiated MSCs. Conclusions: The interaction between vascularity and stem cells remains complex, however, this study provides some insight into its synergistic mechanisms. The combination of surgical angiogenesis with undifferentiated MSCs specifically, results in the greatest increase in revascularization, size of vessels, and stimulation of vessels to reach the middle longitudinal third of the nerve allograft.
AB - Introduction: A detailed three-dimensional (3D) evaluation of microvasculature is evolving to be a powerful tool, providing mechanistic understanding of angiomodulating strategies. The aim of this study was to evaluate the microvascular architecture of nerve allografts after combined stem cell delivery and surgical angiogenesis in a rat sciatic nerve defect model. Materials and Methods: In 25 Lewis rats, sciatic nerve gaps were repaired with (i) autografts, (ii) allografts, (iii) allografts wrapped in a pedicled superficial inferior epigastric artery fascia (SIEF) flap to provide surgical angiogenesis, combined with (iv) undifferentiated mesenchymal stem cells (MSC) and (v) MSCs differentiated into Schwann cell-like cells. At two weeks, vascular volume was measured using microcomputed tomography, and percentage and volume of vessels at different diameters were evaluated and compared with controls. Results: The vascular volume was significantly greatest in allografts treated with undifferentiated MSCs and surgical angiogenesis combined as compared to all experimental groups (P<0.01 as compared to autografts, P<0.0001 to allografts, and P<0.05 to SIEF and SIEF combined with differentiated MSCs, respectively). Volume and diameters of vessel segments in nerve allografts were enhanced by surgical angiogenesis. These distributions were further improved when surgical angiogenesis was combined with stem cells, with greatest increase found when combined with undifferentiated MSCs. Conclusions: The interaction between vascularity and stem cells remains complex, however, this study provides some insight into its synergistic mechanisms. The combination of surgical angiogenesis with undifferentiated MSCs specifically, results in the greatest increase in revascularization, size of vessels, and stimulation of vessels to reach the middle longitudinal third of the nerve allograft.
KW - Differentiation
KW - Nerve revascularization
KW - Peripheral nerve repair
KW - Processed nerve allograft
KW - Stem cells
KW - Surgical angiogenesis
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U2 - 10.1016/j.bjps.2020.12.039
DO - 10.1016/j.bjps.2020.12.039
M3 - Article
C2 - 33436338
AN - SCOPUS:85099209060
SN - 1748-6815
VL - 74
SP - 1919
EP - 1930
JO - Journal of Plastic, Reconstructive and Aesthetic Surgery
JF - Journal of Plastic, Reconstructive and Aesthetic Surgery
IS - 8
ER -