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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

Heat Map of proteins from control, lesion, R1 (rostral segment adjacent to central lesion) at 7 and 10 days (7D and 10D), and C1 (caudal segment adjacent to central lesion) at 7 and 10 days.Green-subexpression, red-overexpression. (a) Protein cluster overexpressed at 7 days compared to 10 days. (b) Protein cluster overexpressed in C1 at 7 days compared to R1 at 7D. (c) Protein cluster subexpressed in R1 at 7D compared to C1 at 7D. (d) Protein cluster subexpressed in C1 at 7D compared to R1 at 7D. (e) Protein cluster overexpressed in R1 at 7D compared to C1 at 7D. (f) Protein cluster subexpressed at 10D compared to 7D. (g) Protein cluster overexpressed at 10D in C1.
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f1: Heat Map of proteins from control, lesion, R1 (rostral segment adjacent to central lesion) at 7 and 10 days (7D and 10D), and C1 (caudal segment adjacent to central lesion) at 7 and 10 days.Green-subexpression, red-overexpression. (a) Protein cluster overexpressed at 7 days compared to 10 days. (b) Protein cluster overexpressed in C1 at 7 days compared to R1 at 7D. (c) Protein cluster subexpressed in R1 at 7D compared to C1 at 7D. (d) Protein cluster subexpressed in C1 at 7D compared to R1 at 7D. (e) Protein cluster overexpressed in R1 at 7D compared to C1 at 7D. (f) Protein cluster subexpressed at 10D compared to 7D. (g) Protein cluster overexpressed at 10D in C1.

Mentions: Spinal cord tissues, the rostral, lesion and caudal segments, were collected at 7 and 10 days after lesion and were subjected to tissue microproteomic, MaxQuant proteins analyses followed by Perseus allowed to statistically validate the identification and performed clustering. Figure 1 clearly shows that the control tissue is on a separate branch from lesion, rostral and caudal segments. The time course study reflected that 7 and 10 days are separated from each other. Comparison of the data obtained at 7 days between rostral and caudal segments clearly shows a common cluster of over-expressed groups of proteins (Fig. 1a) and four different clusters between the rostral and caudal of over- or sub-expressed protein groups (Fig. 1b–e). Proteins overexpressed at 7 days (Fig. 1a) are sub-expressed at 10 days (Fig. 1f). Only a cluster of proteins is differentially overexpressed at the caudal level (Fig. 1g). Specific proteins overexpressed in lesion, rostral and caudal segments are presented in Table 1. Radixin, Neural cell adhesion molecule, COP9 signalosome complex (CSN); Cofilin 2; AP-2, dynamin-like, Rab-7a, GST_P are specific proteins that are overexpressed only in caudal regions at 7 and 10 days. In rostral segment 7 and 10 days after SCI, amphiphysin, hydroxyacyl glutathione hydrolase, inositol monophosphatase, Neurofilament heavy polypeptide, Glycogen phosphorylase, Superoxide dismutase [Cu-Zn], phosphoglycerate mutase 1, septin 8, microtubule-associated protein 1A, CD59 glycoprotein, LETM1 and EF-hand domain-containing protein 1, Elongation factor Tu, Succinate dehydrogenase [ubiquinone] flavoprotein subunit, Vesicle-associated membrane protein-associated protein B are the ones specifically overexpressed.


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)

Heat Map of proteins from control, lesion, R1 (rostral segment adjacent to central lesion) at 7 and 10 days (7D and 10D), and C1 (caudal segment adjacent to central lesion) at 7 and 10 days.Green-subexpression, red-overexpression. (a) Protein cluster overexpressed at 7 days compared to 10 days. (b) Protein cluster overexpressed in C1 at 7 days compared to R1 at 7D. (c) Protein cluster subexpressed in R1 at 7D compared to C1 at 7D. (d) Protein cluster subexpressed in C1 at 7D compared to R1 at 7D. (e) Protein cluster overexpressed in R1 at 7D compared to C1 at 7D. (f) Protein cluster subexpressed at 10D compared to 7D. (g) Protein cluster overexpressed at 10D in C1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4562265&req=5

f1: Heat Map of proteins from control, lesion, R1 (rostral segment adjacent to central lesion) at 7 and 10 days (7D and 10D), and C1 (caudal segment adjacent to central lesion) at 7 and 10 days.Green-subexpression, red-overexpression. (a) Protein cluster overexpressed at 7 days compared to 10 days. (b) Protein cluster overexpressed in C1 at 7 days compared to R1 at 7D. (c) Protein cluster subexpressed in R1 at 7D compared to C1 at 7D. (d) Protein cluster subexpressed in C1 at 7D compared to R1 at 7D. (e) Protein cluster overexpressed in R1 at 7D compared to C1 at 7D. (f) Protein cluster subexpressed at 10D compared to 7D. (g) Protein cluster overexpressed at 10D in C1.
Mentions: Spinal cord tissues, the rostral, lesion and caudal segments, were collected at 7 and 10 days after lesion and were subjected to tissue microproteomic, MaxQuant proteins analyses followed by Perseus allowed to statistically validate the identification and performed clustering. Figure 1 clearly shows that the control tissue is on a separate branch from lesion, rostral and caudal segments. The time course study reflected that 7 and 10 days are separated from each other. Comparison of the data obtained at 7 days between rostral and caudal segments clearly shows a common cluster of over-expressed groups of proteins (Fig. 1a) and four different clusters between the rostral and caudal of over- or sub-expressed protein groups (Fig. 1b–e). Proteins overexpressed at 7 days (Fig. 1a) are sub-expressed at 10 days (Fig. 1f). Only a cluster of proteins is differentially overexpressed at the caudal level (Fig. 1g). Specific proteins overexpressed in lesion, rostral and caudal segments are presented in Table 1. Radixin, Neural cell adhesion molecule, COP9 signalosome complex (CSN); Cofilin 2; AP-2, dynamin-like, Rab-7a, GST_P are specific proteins that are overexpressed only in caudal regions at 7 and 10 days. In rostral segment 7 and 10 days after SCI, amphiphysin, hydroxyacyl glutathione hydrolase, inositol monophosphatase, Neurofilament heavy polypeptide, Glycogen phosphorylase, Superoxide dismutase [Cu-Zn], phosphoglycerate mutase 1, septin 8, microtubule-associated protein 1A, CD59 glycoprotein, LETM1 and EF-hand domain-containing protein 1, Elongation factor Tu, Succinate dehydrogenase [ubiquinone] flavoprotein subunit, Vesicle-associated membrane protein-associated protein B are the ones specifically overexpressed.

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