Decellularized brain matrix enhances macrophage polarization and functional improvements in rat spinal cord injury

Hong, Jongbae; Seo, Yoojin; Davaa, Ganchimeg; Kim, Hae Won; Kim, Soo Hyun; Hyun, Jung Keun

doi:10.1016/j.actbio.2019.11.012

Cited by 93 publications

(86 citation statements)

References 58 publications

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“…For CNS repair, ECM hydrogels derived from porcine brain, spinal cord, or urinary bladder has been evaluated in in vitro as well as in vivo studies ( Crapo et al, 2014 ; Hong et al, 2020 ). We demonstrated that ECM hydrogels derived from decellularized porcine spinal cord and urinary bladder tissues filled the lesion, had an effect on the immune response, and created a stimulatory substrate for in vivo neural tissue repair after SCI.…”

Section: Biomaterials In Combination With Mscs In Sci Treatmentmentioning

confidence: 99%

Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis

Syková

Cizkova

Kubinová

2021

Front. Cell Dev. Biol.

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Preclinical and clinical studies with various stem cells, their secretomes, and extracellular vesicles (EVs) indicate their use as a promising strategy for the treatment of various diseases and tissue defects, including neurodegenerative diseases such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). Autologous and allogenic mesenchymal stem cells (MSCs) are so far the best candidates for use in regenerative medicine. Here we review the effects of the implantation of MSCs (progenitors of mesodermal origin) in animal models of SCI and ALS and in clinical studies. MSCs possess multilineage differentiation potential and are easily expandable in vitro. These cells, obtained from bone marrow (BM), adipose tissue, Wharton jelly, or even other tissues, have immunomodulatory and paracrine potential, releasing a number of cytokines and factors which inhibit the proliferation of T cells, B cells, and natural killer cells and modify dendritic cell activity. They are hypoimmunogenic, migrate toward lesion sites, induce better regeneration, preserve perineuronal nets, and stimulate neural plasticity. There is a wide use of MSC systemic application or MSCs seeded on scaffolds and tissue bridges made from various synthetic and natural biomaterials, including human decellularized extracellular matrix (ECM) or nanofibers. The positive effects of MSC implantation have been recorded in animals with SCI lesions and ALS. Moreover, promising effects of autologous as well as allogenic MSCs for the treatment of SCI and ALS were demonstrated in recent clinical studies.

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Section: Biomaterials In Combination With Mscs In Sci Treatmentmentioning

confidence: 99%

Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis

Syková

Cizkova

Kubinová

2021

Front. Cell Dev. Biol.

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“…All rats walked on a metal runway (2.5 cm between grids) from left to right three times, and their movements were captured with a digital camcorder. The score was calculated as follows: ladder score (%) = erroneous steps of hind limb/total steps of hind limb × 100 [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the effects of differences in silicone hardness on rat model of lumbar spinal stenosis

et al. 2021

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Lumbar spinal stenosis (LSS), one of the most commonly reported spinal disorders, can cause loss of sensation and dyskinesia. In currently used animal models of LSS, the spinal cord is covered entirely with a silicone sheet, or block-shaped silicone is inserted directly into the spinal canal after laminectomy. However, the effects of differences between these implant materials have not been studied. We assessed the degree of damage and locomotor function of an LSS model in Sprague-Dawley rats using silicone blocks of varying hardness (70, 80, and 90 kPa) implanted at the L4 level. In sham rats, the spinal cord remained intact; in LSS rats, the spinal cord was increasingly compressed by the mechanical pressure of the silicone blocks as hardness increased. Inflammatory cells were not evident in sham rats, but numerous inflammatory cells were observed around the implanted silicone block in LSS rats. CD68+ cell quantification revealed increases in the inflammatory response in a hardness-dependent manner in LSS rats. Compared with those in sham rats, proinflammatory cytokine levels were significantly elevated in a hardness-dependent manner, and locomotor function was significantly decreased, in LSS rats. Overall, this study showed that hardness could be used as an index to control the severity of nerve injury induced by silicone implants.

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“…Two independent observers analyzed the motion of the hindlimbs for 4 minutes in an open field (cylindrical acrylic box; 90 cm diameter, 15 cm height) and the average value was used as the representative score. The ladder walking test was performed to assess the balancing ability of the rats [20]. All rats walked on the metal runway (2.5 cm between grids) from left to right three times and their movements were captured with a digital camcorder.…”

Section: Functional Assessmentsmentioning

confidence: 99%

IL-1β promotes disc degeneration and inflammation through direct injection of intervertebral disc in a rat lumbar disc herniation model

et al. 2021

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BACKGROUND CONTEXT: Lumbar intervertebral disk herniation (LDH) is a common disease that causes low back pain, radiating leg pain, and sensory impairment. Preclinical studies rely heavily upon standardized animal models of human diseases to predict clinical treatment efficacy and to identify and investigate potential adverse events in human subjects. The current method for making the LDH model involves harvesting the nucleus pulposus (NP) from autologous coccygeal disks and applying to the lumbar nerve roots just proximal to the corresponding dorsal root ganglion. However, this surgical method generates a model that exhibits very different characteristics of disk herniation than that observed in human. PURPOSE: To produce a rat LDH model that better resembles disk herniation in humans and a standardized and uniform LDH model using Interleukin-1 beta (IL-1b). STUDY DESIGN: Experimental rat LDH model. METHODS: We exposed the L5−6 disk dorsolaterally on the right side through hemi-laminectomy without nerve compression. Herniation was initiated by puncturing the exposed disk with a 30-gauge needle at a depth of 4 mm. Interleukin-1 beta (IL-1b) was injected simultaneously to heighten the pathological processes of disk degeneration, including inflammatory responses, matrix destruction, and herniation of the NP. We performed histological staining to assess morphological changes, immunohistochemistry to analyze inflammation-and pain-related expression within and around the puncture site of the L5−6 disk, and real-time polymerase chain reaction to examine expression of markers for degenerative processes. In addition, we performed locomotor tests on the rats. RESULTS: We found that the IL-1b groups showed that the border between the annulus fibrosis and nucleus pulposus was severely interrupted compared to that of the control (puncture only) group. And, the injection of IL-1b leads to accelerated disk degeneration and inflammation in a more consistent manner in LDH model. Functional deficit was consistently induced by puncturing and injection of IL-1b in the exposed disk. CONCLUSIONS: The method proposed here can be used as an index to control the severity of disk degeneration and inflammation through the injected IL-1b concentration concurrent with surgically induced herniation. CLINICAL SIGNIFICANCE: Our proposed model may facilitate research in drug development to evaluate the efficacy of potential therapeutic agents for disk herniation and neuropathic pain and may also be used for nonclinical studies to more accurately assess the effectiveness of various treatment strategies according to the severity of disk degeneration.

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Decellularized brain matrix enhances macrophage polarization and functional improvements in rat spinal cord injury

Cited by 93 publications

References 58 publications

Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis

Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis

Evaluation of the effects of differences in silicone hardness on rat model of lumbar spinal stenosis

IL-1β promotes disc degeneration and inflammation through direct injection of intervertebral disc in a rat lumbar disc herniation model

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