Abstract
Neurotrophins and the transplantation of bone marrow-derived stromal cells (MSCs) are both candidate therapies targeting experimental and clinical spinal cord injury (SCI). While some studies have suggested the ability of MSCs to transdifferentiate into neural cells, other SCI studies have proposed anti-inflammatory and other mechanisms underlying established beneficial effects. We grafted rat MSCs genetically modified to express MNTS1, a multineurotrophin that binds TrkA, TrkB and TrkC, and p75NTR receptors or MSC-MNTS1p75<sup>-</sup> that binds mainly to the Trk receptors. Seven days after contusive SCI, PBS-only, GFP-MSC, MSC-MNTS1/GFP, or MSC-MNTS1/p75<sup>-</sup>/GFP was delivered into the injury epicenter. All transplanted groups showed reduced inflammation and cystic cavity size compared to control SCI rats. Interestingly, transplantation of the MSC-MNTS1 and MSC-MNTS1/p75<sup>-</sup>, but not the naïve MSCs, enhanced axonal growth and significantly prevented cutaneous hypersensitivity after SCI. Moreover, transplantation of MSC-MNTS1/p75<sup>-</sup> promoted angiogenesis and modified glial scar formation. These findings suggest that MSCs transduced with a multineurotrophin are effective in promoting cell growth and improving sensory function after SCI. These novel data also provide insight into the neurotrophin-receptor-dependent mechanisms through which cellular transplantation leads to functional improvement after experimental SCI.
| Original language | English (US) |
|---|---|
| Title of host publication | Neuroprotection and Regeneration of the Spinal Cord |
| Publisher | Springer Japan |
| Pages | 255-268 |
| Number of pages | 14 |
| Volume | 9784431545026 |
| ISBN (Print) | 9784431545026, 4431545018, 9784431545019 |
| DOIs | |
| State | Published - Nov 1 2013 |
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Keywords
- Axonal regeneration
- Multineurotrophin
- Rat bone marrow stromal cells
- Spinal cord injury
- Transplantation
ASJC Scopus subject areas
- Medicine(all)
Cite this
The effects of mesenchymal stem cell-transduced multineurotrophin to improve function following spinal cord injury. / Kumagai, Gentaro; Dalton Dietrich, W.
Neuroprotection and Regeneration of the Spinal Cord. Vol. 9784431545026 Springer Japan, 2013. p. 255-268.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - The effects of mesenchymal stem cell-transduced multineurotrophin to improve function following spinal cord injury
AU - Kumagai, Gentaro
AU - Dalton Dietrich, W.
PY - 2013/11/1
Y1 - 2013/11/1
N2 - Neurotrophins and the transplantation of bone marrow-derived stromal cells (MSCs) are both candidate therapies targeting experimental and clinical spinal cord injury (SCI). While some studies have suggested the ability of MSCs to transdifferentiate into neural cells, other SCI studies have proposed anti-inflammatory and other mechanisms underlying established beneficial effects. We grafted rat MSCs genetically modified to express MNTS1, a multineurotrophin that binds TrkA, TrkB and TrkC, and p75NTR receptors or MSC-MNTS1p75- that binds mainly to the Trk receptors. Seven days after contusive SCI, PBS-only, GFP-MSC, MSC-MNTS1/GFP, or MSC-MNTS1/p75-/GFP was delivered into the injury epicenter. All transplanted groups showed reduced inflammation and cystic cavity size compared to control SCI rats. Interestingly, transplantation of the MSC-MNTS1 and MSC-MNTS1/p75-, but not the naïve MSCs, enhanced axonal growth and significantly prevented cutaneous hypersensitivity after SCI. Moreover, transplantation of MSC-MNTS1/p75- promoted angiogenesis and modified glial scar formation. These findings suggest that MSCs transduced with a multineurotrophin are effective in promoting cell growth and improving sensory function after SCI. These novel data also provide insight into the neurotrophin-receptor-dependent mechanisms through which cellular transplantation leads to functional improvement after experimental SCI.
AB - Neurotrophins and the transplantation of bone marrow-derived stromal cells (MSCs) are both candidate therapies targeting experimental and clinical spinal cord injury (SCI). While some studies have suggested the ability of MSCs to transdifferentiate into neural cells, other SCI studies have proposed anti-inflammatory and other mechanisms underlying established beneficial effects. We grafted rat MSCs genetically modified to express MNTS1, a multineurotrophin that binds TrkA, TrkB and TrkC, and p75NTR receptors or MSC-MNTS1p75- that binds mainly to the Trk receptors. Seven days after contusive SCI, PBS-only, GFP-MSC, MSC-MNTS1/GFP, or MSC-MNTS1/p75-/GFP was delivered into the injury epicenter. All transplanted groups showed reduced inflammation and cystic cavity size compared to control SCI rats. Interestingly, transplantation of the MSC-MNTS1 and MSC-MNTS1/p75-, but not the naïve MSCs, enhanced axonal growth and significantly prevented cutaneous hypersensitivity after SCI. Moreover, transplantation of MSC-MNTS1/p75- promoted angiogenesis and modified glial scar formation. These findings suggest that MSCs transduced with a multineurotrophin are effective in promoting cell growth and improving sensory function after SCI. These novel data also provide insight into the neurotrophin-receptor-dependent mechanisms through which cellular transplantation leads to functional improvement after experimental SCI.
KW - Axonal regeneration
KW - Multineurotrophin
KW - Rat bone marrow stromal cells
KW - Spinal cord injury
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=84930701377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930701377&partnerID=8YFLogxK
U2 - 10.1007/978-4-431-54502-6_21
DO - 10.1007/978-4-431-54502-6_21
M3 - Chapter
AN - SCOPUS:84930701377
SN - 9784431545026
SN - 4431545018
SN - 9784431545019
VL - 9784431545026
SP - 255
EP - 268
BT - Neuroprotection and Regeneration of the Spinal Cord
PB - Springer Japan
ER -