A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord
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A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord. / Hoeber, Jan; Konig, Niclas; Trolle, Carl; Lekholm, Emilia; Zhou, Chunfang; Pankratova, Stanislava; Akesson, Elisabet; Fredriksson, Robert; Aldskogius, Hakan; Kozlova, Elena N.
In: Stem Cells and Development, Vol. 26, No. 14, 2017, p. 1065-1077.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord
AU - Hoeber, Jan
AU - Konig, Niclas
AU - Trolle, Carl
AU - Lekholm, Emilia
AU - Zhou, Chunfang
AU - Pankratova, Stanislava
AU - Akesson, Elisabet
AU - Fredriksson, Robert
AU - Aldskogius, Hakan
AU - Kozlova, Elena N.
PY - 2017
Y1 - 2017
N2 - Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (MesoMIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along “bridges” formed by migrating stem cells. Coimplantation of MesoMIM prevented stem cell migration, “bridges” were not formed, and sensory axons failed to enter the spinal cord. MesoMIM applied alone supported sensory axons ingrowth, but without affecting glial scar formation. In vitro, the presence of MesoMIM significantly impaired migration of hscNSPC without affecting their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular “bridges” in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient alternative way to induce sensory axon regeneration, and (3) a combinatorial approach of individually beneficial components is not necessarily additive, but can be counterproductive for axonal growth.
AB - Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (MesoMIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along “bridges” formed by migrating stem cells. Coimplantation of MesoMIM prevented stem cell migration, “bridges” were not formed, and sensory axons failed to enter the spinal cord. MesoMIM applied alone supported sensory axons ingrowth, but without affecting glial scar formation. In vitro, the presence of MesoMIM significantly impaired migration of hscNSPC without affecting their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular “bridges” in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient alternative way to induce sensory axon regeneration, and (3) a combinatorial approach of individually beneficial components is not necessarily additive, but can be counterproductive for axonal growth.
KW - spinal cord regeneration
KW - stem cell transplantation
KW - neural stem cells
KW - biomimetics
U2 - 10.1089/scd.2017.0019
DO - 10.1089/scd.2017.0019
M3 - Journal article
C2 - 28562227
VL - 26
SP - 1065
EP - 1077
JO - Stem Cells and Development
JF - Stem Cells and Development
SN - 1547-3287
IS - 14
ER -
ID: 182485830