TY - JOUR
T1 - Typical and atypical properties of peripheral nerve allografts enable novel strategies to repair segmental-loss injuries
AU - Bittner, George D.
AU - Bushman, Jared S.
AU - Ghergherehchi, Cameron L.
AU - Roballo, Kelly C.S.
AU - Shores, Jaimie T.
AU - Smith, Tyler A.
N1 - Funding Information:
This work was supported by grants from the Lone Star Paralysis Foundation and NIH R01NS081063 to GDB and Department of Defense award W81XWH-19-2-0054 to GDB and JTS. This work was also supported by University of Wyoming Startup funds, United States Department of Defense grant W81XWH-17-1-0402, the University of Wyoming Sensory Biology COBRE under National Institutes of Health (NIH) award number 5P20GM121310-02, the National Institute of General Medical Sciences of the NIH under Award Number P20GM103432 to JSB. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US Department of Defense, NIH, Johns Hopkins University, The University of Texas, or the University of Wyoming.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - We review data showing that peripheral nerve injuries (PNIs) that involve the loss of a nerve segment are the most common type of traumatic injury to nervous systems. Segmental-loss PNIs have a poor prognosis compared to other injuries, especially when one or more mixed motor/sensory nerves are involved and are typically the major source of disability associated with extremities that have sustained other injuries. Relatively little progress has been made, since the treatment of segmental loss PNIs with cable autografts that are currently the gold standard for repair has slow and incomplete (often non-existent) functional recovery. Viable peripheral nerve allografts (PNAs) to repair segmental-loss PNIs have not been experimentally or clinically useful due to their immunological rejection, Wallerian degeneration (WD) of anucleate donor graft and distal host axons, and slow regeneration of host axons, leading to delayed re-innervation and producing atrophy or degeneration of distal target tissues. However, two significant advances have recently been made using viable PNAs to repair segmental-loss PNIs: (1) hydrogel release of Treg cells that reduce the immunological response and (2) PEG-fusion of donor PNAs that reduce the immune response, reduce and/or suppress much WD, immediately restore axonal conduction across the donor graft and re-innervate many target tissues, and restore much voluntary behavioral functions within weeks, sometimes to levels approaching that of uninjured nerves. We review the rather sparse cellular/biochemical data for rejection of conventional PNAs and their acceptance following Treg hydrogel and PEG-fusion of PNAs, as well as cellular and systemic data for their acceptance and remarkable behavioral recovery in the absence of tissue matching or immune suppression. We also review typical and atypical characteristics of PNAs compared with other types of tissue or organ allografts, problems and potential solutions for PNA use and storage, clinical implications and commercial availability of PNAs, and future possibilities for PNAs to repair segmental-loss PNIs.
AB - We review data showing that peripheral nerve injuries (PNIs) that involve the loss of a nerve segment are the most common type of traumatic injury to nervous systems. Segmental-loss PNIs have a poor prognosis compared to other injuries, especially when one or more mixed motor/sensory nerves are involved and are typically the major source of disability associated with extremities that have sustained other injuries. Relatively little progress has been made, since the treatment of segmental loss PNIs with cable autografts that are currently the gold standard for repair has slow and incomplete (often non-existent) functional recovery. Viable peripheral nerve allografts (PNAs) to repair segmental-loss PNIs have not been experimentally or clinically useful due to their immunological rejection, Wallerian degeneration (WD) of anucleate donor graft and distal host axons, and slow regeneration of host axons, leading to delayed re-innervation and producing atrophy or degeneration of distal target tissues. However, two significant advances have recently been made using viable PNAs to repair segmental-loss PNIs: (1) hydrogel release of Treg cells that reduce the immunological response and (2) PEG-fusion of donor PNAs that reduce the immune response, reduce and/or suppress much WD, immediately restore axonal conduction across the donor graft and re-innervate many target tissues, and restore much voluntary behavioral functions within weeks, sometimes to levels approaching that of uninjured nerves. We review the rather sparse cellular/biochemical data for rejection of conventional PNAs and their acceptance following Treg hydrogel and PEG-fusion of PNAs, as well as cellular and systemic data for their acceptance and remarkable behavioral recovery in the absence of tissue matching or immune suppression. We also review typical and atypical characteristics of PNAs compared with other types of tissue or organ allografts, problems and potential solutions for PNA use and storage, clinical implications and commercial availability of PNAs, and future possibilities for PNAs to repair segmental-loss PNIs.
KW - Immunosuppression
KW - Peripheral nerve allografts
KW - Polyethylene glycol (PEG)
KW - T cells
KW - Wallerian degeneration
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U2 - 10.1186/s12974-022-02395-0
DO - 10.1186/s12974-022-02395-0
M3 - Review article
C2 - 35227261
AN - SCOPUS:85125621597
SN - 1742-2094
VL - 19
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
IS - 1
M1 - 60
ER -