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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

Baseline expression of GFAP-positive astrocytes with the characteristic round nuclei and slender, long processes distributed throughout both white and gray matter was revealed in Sham animals 49D post-injury.SCI and vehicle/saline treatment induced increase in GFAP immunohistochemical staining associated with cellular transformation; swollen hypertrophic appearance and short, dick processes indicating activated phenotype. Similarly alginate slightly increased the GFAP density but positive cells were without hypertrophic appearance. Scale bars = 100 μm (A), 50 μm (B).
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f13: Baseline expression of GFAP-positive astrocytes with the characteristic round nuclei and slender, long processes distributed throughout both white and gray matter was revealed in Sham animals 49D post-injury.SCI and vehicle/saline treatment induced increase in GFAP immunohistochemical staining associated with cellular transformation; swollen hypertrophic appearance and short, dick processes indicating activated phenotype. Similarly alginate slightly increased the GFAP density but positive cells were without hypertrophic appearance. Scale bars = 100 μm (A), 50 μm (B).

Mentions: Baseline expression of GFAP-positive astrocytes with the characteristic round small soma and slender, long processes were seen in Sham spinal cord distributed throughout white and grey matter (Ros/11 ± 1.8, Ros-Centre/10.81 ± 1.41, Centre-Caud/10.81 ± 1.41, Caud/12.6 ± 1.6) (Fig. 13). The significant response of astrocytes that resulted in increased density and change of cellular morphology was observed following SCI and saline delivery (***P < 0.001, **P < 0.01, *P < 0.05). Astrocytes assumed increased GFAP staining with subsequent cellular transformation into swollen hypertrophic appearance and short, thick processes indicating activated phenotype (Fig. 13). Similarly, alginate biomaterial treatment alone or with affinity-bound bFGF/EGF induced appearance of activated astrocytes, but with poorer ramification as seen after saline delivery (Fig. 13). The densitometry analysis revealed differences between the individual parts of 1.6 cm sections (Ros, Ros/Central, Central/Caudal, Caudal) of spinal cord. The highest positivity of GFAP was measured within Centro-Caudal site in all experimental groups (SCI+ALG+GFs: Ros/11 ± 1.8, Ros-Centre/10.81 ± 1.41, Centre-caud/10.81 ± 1.41, Caud/12.6 ± 1.6; SCI+ALG: Ros/14.9 ± 4.1, Ros-Centre/13.4 ± 3.6, Centre-Caud/16 ± 3.5, Caud/13.8 ± 3.1; SCI+SAL: Ros/17.9 ± 2.2, Ros-Centre/18 ± 3.7, Centre-Caud/21.5 ± 3.9, Caud/21.4 ± 1.6) (Supplementary Figure 6). The quantification of GFAP immunoreactivity on transverse sections from rostral and caudal segments of spinal cord also confirmed an increase in immunoreactivity caudally to the lesion site especially after saline delivery (Rostrally: 14.8 ± 4.2/SCI+ALG+GFs, 14.9 ± 4.9/SCI+ALG,18.11 ± 1.6/SCI+SAL, 13.6 ± 1.6/Sham; Caudally: 16.3 ± 3/SCI+ALG+GFs, 15.3 ± 3.4/SCI+ALG, 17.6 ± 2.4/SCI+SAL, 13.2 ± 0.5/Sham). Differences in GFAP density between experimental groups in rostro-caudal segments were without observed significant differences (Supplementary Figure 6).


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)

Baseline expression of GFAP-positive astrocytes with the characteristic round nuclei and slender, long processes distributed throughout both white and gray matter was revealed in Sham animals 49D post-injury.SCI and vehicle/saline treatment induced increase in GFAP immunohistochemical staining associated with cellular transformation; swollen hypertrophic appearance and short, dick processes indicating activated phenotype. Similarly alginate slightly increased the GFAP density but positive cells were without hypertrophic appearance. Scale bars = 100 μm (A), 50 μm (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f13: Baseline expression of GFAP-positive astrocytes with the characteristic round nuclei and slender, long processes distributed throughout both white and gray matter was revealed in Sham animals 49D post-injury.SCI and vehicle/saline treatment induced increase in GFAP immunohistochemical staining associated with cellular transformation; swollen hypertrophic appearance and short, dick processes indicating activated phenotype. Similarly alginate slightly increased the GFAP density but positive cells were without hypertrophic appearance. Scale bars = 100 μm (A), 50 μm (B).
Mentions: Baseline expression of GFAP-positive astrocytes with the characteristic round small soma and slender, long processes were seen in Sham spinal cord distributed throughout white and grey matter (Ros/11 ± 1.8, Ros-Centre/10.81 ± 1.41, Centre-Caud/10.81 ± 1.41, Caud/12.6 ± 1.6) (Fig. 13). The significant response of astrocytes that resulted in increased density and change of cellular morphology was observed following SCI and saline delivery (***P < 0.001, **P < 0.01, *P < 0.05). Astrocytes assumed increased GFAP staining with subsequent cellular transformation into swollen hypertrophic appearance and short, thick processes indicating activated phenotype (Fig. 13). Similarly, alginate biomaterial treatment alone or with affinity-bound bFGF/EGF induced appearance of activated astrocytes, but with poorer ramification as seen after saline delivery (Fig. 13). The densitometry analysis revealed differences between the individual parts of 1.6 cm sections (Ros, Ros/Central, Central/Caudal, Caudal) of spinal cord. The highest positivity of GFAP was measured within Centro-Caudal site in all experimental groups (SCI+ALG+GFs: Ros/11 ± 1.8, Ros-Centre/10.81 ± 1.41, Centre-caud/10.81 ± 1.41, Caud/12.6 ± 1.6; SCI+ALG: Ros/14.9 ± 4.1, Ros-Centre/13.4 ± 3.6, Centre-Caud/16 ± 3.5, Caud/13.8 ± 3.1; SCI+SAL: Ros/17.9 ± 2.2, Ros-Centre/18 ± 3.7, Centre-Caud/21.5 ± 3.9, Caud/21.4 ± 1.6) (Supplementary Figure 6). The quantification of GFAP immunoreactivity on transverse sections from rostral and caudal segments of spinal cord also confirmed an increase in immunoreactivity caudally to the lesion site especially after saline delivery (Rostrally: 14.8 ± 4.2/SCI+ALG+GFs, 14.9 ± 4.9/SCI+ALG,18.11 ± 1.6/SCI+SAL, 13.6 ± 1.6/Sham; Caudally: 16.3 ± 3/SCI+ALG+GFs, 15.3 ± 3.4/SCI+ALG, 17.6 ± 2.4/SCI+SAL, 13.2 ± 0.5/Sham). Differences in GFAP density between experimental groups in rostro-caudal segments were without observed significant differences (Supplementary Figure 6).

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