TY - JOUR
T1 - Activation of Intrinsic Growth State Enhances Host Axonal Regeneration into Neural Progenitor Cell Grafts
AU - Kumamaru, Hiromi
AU - Lu, Paul
AU - Rosenzweig, Ephron S.
AU - Tuszynski, Mark H.
N1 - Funding Information:
We thank L. Graham, E. Staufenberg, and J. Weber for technical assistance; T. Müller and C. Birchmeier, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany, for providing TLX3 antibody. Human 566RSC-UBQT NPCs were a gift from NeuralStem. Supported by the Veterans Administration Gordon Mansfield Spinal Cord Injury Consortium IP50RX001045 (to M.H.T.); the NIH (NS042291, NS104442, and EB014986, to M.H.T.); the Craig H. Neilsen Foundation (to H.K. and P.L.); the Japan Society for the Promotion of Science (to H.K.); the Bernard and Anne Spitzer Charitable Trust (to M.H.T.); the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to M.H.T.); and the California National Primate Research Center funded by the NIH (NCRR P51 OD011107-56).
Funding Information:
We thank L. Graham, E. Staufenberg, and J. Weber for technical assistance; T. Müller and C. Birchmeier, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany, for providing TLX3 antibody. Human 566RSC-UBQT NPCs were a gift from NeuralStem. Supported by the Veterans Administration Gordon Mansfield Spinal Cord Injury Consortium IP50RX001045 (to M.H.T.); the NIH ( NS042291 , NS104442 , and EB014986 , to M.H.T.); the Craig H. Neilsen Foundation (to H.K. and P.L.); the Japan Society for the Promotion of Science (to H.K.); the Bernard and Anne Spitzer Charitable Trust (to M.H.T.); the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to M.H.T.); and the California National Primate Research Center funded by the NIH (NCRR P51 OD011107-56 ).
Publisher Copyright:
© 2018 The Author(s)
PY - 2018/10/9
Y1 - 2018/10/9
N2 - Axonal regeneration after spinal cord injury (SCI) can be enhanced by activation of the intrinsic neuronal growth state and, separately, by placement of growth-enabling neural progenitor cell (NPC) grafts into lesion sites. Indeed, NPC grafts support regeneration of all host axonal projections innervating the normal spinal cord. However, some host axons regenerate only short distances into grafts. We examined whether activation of the growth state of the host injured neuron would elicit greater regeneration into NPC grafts. Rats received NPC grafts into SCI lesions in combination with peripheral “conditioning” lesions. Six weeks later, conditioned host sensory axons exhibited a significant, 9.6-fold increase in regeneration into the lesion/graft site compared with unconditioned axons. Regeneration was further enhanced 1.6-fold by enriching NPC grafts with phenotypically appropriate sensory neuronal targets. Thus, activation of the intrinsic host neuronal growth state and manipulation of the graft environment enhance axonal regeneration after SCI. Kumamaru and colleagues demonstrate that activation of intrinsic growth state robustly enhances host sensory axonal regeneration into neural stem cell grafts. Regeneration of lesioned host sensory axons was further enhanced by enriching neural stem cell grafts with phenotypically appropriate sensory neuron targets.
AB - Axonal regeneration after spinal cord injury (SCI) can be enhanced by activation of the intrinsic neuronal growth state and, separately, by placement of growth-enabling neural progenitor cell (NPC) grafts into lesion sites. Indeed, NPC grafts support regeneration of all host axonal projections innervating the normal spinal cord. However, some host axons regenerate only short distances into grafts. We examined whether activation of the growth state of the host injured neuron would elicit greater regeneration into NPC grafts. Rats received NPC grafts into SCI lesions in combination with peripheral “conditioning” lesions. Six weeks later, conditioned host sensory axons exhibited a significant, 9.6-fold increase in regeneration into the lesion/graft site compared with unconditioned axons. Regeneration was further enhanced 1.6-fold by enriching NPC grafts with phenotypically appropriate sensory neuronal targets. Thus, activation of the intrinsic host neuronal growth state and manipulation of the graft environment enhance axonal regeneration after SCI. Kumamaru and colleagues demonstrate that activation of intrinsic growth state robustly enhances host sensory axonal regeneration into neural stem cell grafts. Regeneration of lesioned host sensory axons was further enhanced by enriching neural stem cell grafts with phenotypically appropriate sensory neuron targets.
UR - http://www.scopus.com/inward/record.url?scp=85054751072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054751072&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2018.08.009
DO - 10.1016/j.stemcr.2018.08.009
M3 - Article
C2 - 30197116
AN - SCOPUS:85054751072
VL - 11
SP - 861
EP - 868
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 4
ER -