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Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair.

Grulova I, Slovinska L, Blaško J, Devaux S, Wisztorski M, Salzet M, Fournier I, Kryukov O, Cohen S, Cizkova D - Sci Rep (2015)

Bottom Line: In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion.Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed.Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG+GFs), compared to SCI animals without biomaterial treatment.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurobiology, Center of Excellence for Brain Research, Department of Regenerative Medicine and Stem Cell Therapy, Slovak Academy of Sciences, Soltesovej 4-6, 040 01 Kosice, Slovakia.

ABSTRACT
Spinal cord injury (SCI) has been implicated in neural cell loss and consequently functional motor and sensory impairment. In this study, we propose an alginate-based neurobridge enriched with/without trophic growth factors (GFs) that can be utilized as a therapeutic approach for spinal cord repair. The bioavailability of key GFs, such as Epidermal Growth factor (EGF) and basic Fibroblast Growth Factor (bFGF) released from injected alginate biomaterial to the central lesion site significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons (choline acetyltransferase positive motoneurons) and sensory fibres. In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion. Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed. Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG+GFs), compared to SCI animals without biomaterial treatment.

No MeSH data available.


Related in: MedlinePlus

Distribution of synaptophysin positive vesicles (red) in the area of ChAT positive motoneurons (green) of the ventral horns.The density of vesicles after ALG+GFs treatment (C) is increased compared to both sham (A) and ALG without GFs group (B). (D) Quantification has revealed statistical significance only between ALG+GFs group and other experimental groups (SHAM, SCI+SAL, SCI+ALG). (**P < 0.01, ***P < 0.001). Scale bar = 50 μm.
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f7: Distribution of synaptophysin positive vesicles (red) in the area of ChAT positive motoneurons (green) of the ventral horns.The density of vesicles after ALG+GFs treatment (C) is increased compared to both sham (A) and ALG without GFs group (B). (D) Quantification has revealed statistical significance only between ALG+GFs group and other experimental groups (SHAM, SCI+SAL, SCI+ALG). (**P < 0.01, ***P < 0.001). Scale bar = 50 μm.

Mentions: In the spinal cord of Sham and both SCI-SAL and SCI-ALG groups of treated rats, synaptophysin immunoreactivity (SYN+IR) appeared as numerous diffusely distributed fine dots along the surface of motor neurons and their proximal dendrites, and delineated their polygonal contours (Fig. 7A,B). However, after ALG+GFs treatment, the density of SYN+ vesicles around remaining CHAT+ motor neurons of the anterior horns strikingly increased when compared to all experimental groups (Fig. 7C,D). The immunoreactive profiles appeared as coarse granules of different size that were also distributed on motor neuron surface. Quantitative analysis of SYN+ vesicle expressed as % of SYN+ positive vesicles within identical fields of anterior horns in all experimental groups confirmed significant increase in ALG+GFs treated group, particularly caudally to the epicentre of injury (Fig. 7D). Interestingly, we did not see any differences in the density of SYN+ positive vesicles within segments above the lesion site (data not shown).


Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair.

Grulova I, Slovinska L, Blaško J, Devaux S, Wisztorski M, Salzet M, Fournier I, Kryukov O, Cohen S, Cizkova D - Sci Rep (2015)

Distribution of synaptophysin positive vesicles (red) in the area of ChAT positive motoneurons (green) of the ventral horns.The density of vesicles after ALG+GFs treatment (C) is increased compared to both sham (A) and ALG without GFs group (B). (D) Quantification has revealed statistical significance only between ALG+GFs group and other experimental groups (SHAM, SCI+SAL, SCI+ALG). (**P < 0.01, ***P < 0.001). Scale bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562265&req=5

f7: Distribution of synaptophysin positive vesicles (red) in the area of ChAT positive motoneurons (green) of the ventral horns.The density of vesicles after ALG+GFs treatment (C) is increased compared to both sham (A) and ALG without GFs group (B). (D) Quantification has revealed statistical significance only between ALG+GFs group and other experimental groups (SHAM, SCI+SAL, SCI+ALG). (**P < 0.01, ***P < 0.001). Scale bar = 50 μm.
Mentions: In the spinal cord of Sham and both SCI-SAL and SCI-ALG groups of treated rats, synaptophysin immunoreactivity (SYN+IR) appeared as numerous diffusely distributed fine dots along the surface of motor neurons and their proximal dendrites, and delineated their polygonal contours (Fig. 7A,B). However, after ALG+GFs treatment, the density of SYN+ vesicles around remaining CHAT+ motor neurons of the anterior horns strikingly increased when compared to all experimental groups (Fig. 7C,D). The immunoreactive profiles appeared as coarse granules of different size that were also distributed on motor neuron surface. Quantitative analysis of SYN+ vesicle expressed as % of SYN+ positive vesicles within identical fields of anterior horns in all experimental groups confirmed significant increase in ALG+GFs treated group, particularly caudally to the epicentre of injury (Fig. 7D). Interestingly, we did not see any differences in the density of SYN+ positive vesicles within segments above the lesion site (data not shown).

Bottom Line: In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion.Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed.Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG+GFs), compared to SCI animals without biomaterial treatment.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurobiology, Center of Excellence for Brain Research, Department of Regenerative Medicine and Stem Cell Therapy, Slovak Academy of Sciences, Soltesovej 4-6, 040 01 Kosice, Slovakia.

ABSTRACT
Spinal cord injury (SCI) has been implicated in neural cell loss and consequently functional motor and sensory impairment. In this study, we propose an alginate-based neurobridge enriched with/without trophic growth factors (GFs) that can be utilized as a therapeutic approach for spinal cord repair. The bioavailability of key GFs, such as Epidermal Growth factor (EGF) and basic Fibroblast Growth Factor (bFGF) released from injected alginate biomaterial to the central lesion site significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons (choline acetyltransferase positive motoneurons) and sensory fibres. In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion. Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed. Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG+GFs), compared to SCI animals without biomaterial treatment.

No MeSH data available.


Related in: MedlinePlus