We assessed an injectable gelatin hydrogel containing epidermal growth factor (Gtn-EGF) as a therapy for intracerebral hemorrhage (ICH). ICH was induced in rats via collagenase injection into the striatum. Two weeks later, Gtn-EGF was injected into the cavitary lesion. The hydrogel filled ICH cavities without deforming brain tissue. Immunostaining demonstrated that neural precursor cells could migrate into the matrix, and some of these differentiated into neurons along with the appearance of astrocytes, oligodendrocytes, and endothelial cells. Sensorimotor tests suggested that Gtn-EGF improved neurological recovery. This study provides proof-of-principle that injectable biomaterials may be a translationally relevant approach for treating ICH.
#1Nicole J. Darling(UCLA: University of California, Los Angeles)H-Index: 6
#2Elias Sideris(UCLA: University of California, Los Angeles)H-Index: 5
Last. Tatiana Segura(UCLA: University of California, Los Angeles)H-Index: 41
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Author(s): Darling, Nicole J; Sideris, Elias; Hamada, Naomi; Carmichael, S Thomas; Segura, Tatiana | Abstract: Spatially patterned hydrogels are becoming increasingly popular in the field of regenerative medicine and tissue repair because of their ability to guide cell infiltration and migration. However, postfabrication technologies are usually required to spatially pattern a hydrogel, making these hydrogels difficult to translate into the clinic. Here, an injectable spatially patterned hydroge...
#1Lina R. Nih(UCLA: University of California, Los Angeles)H-Index: 11
#2Shiva Gojgini(UCLA: University of California, Los Angeles)H-Index: 5
Last. Tatiana Segura(UCLA: University of California, Los Angeles)H-Index: 41
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Stroke is the primary cause of disability due to the brain's limited ability to regenerate damaged tissue. After stroke, an increased inflammatory and immune response coupled with severely limited angiogenesis and neuronal growth results in a stroke cavity devoid of normal brain tissue. In the adult, therapeutic angiogenic materials have been used to repair ischaemic tissues through the formation of vascular networks. However, whether a therapeutic angiogenic material can regenerate brain tissue...
#1Lina R. Nih(UCLA: University of California, Los Angeles)H-Index: 11
#2Elias Sideris(UCLA: University of California, Los Angeles)H-Index: 5
Last. Tatiana Segura(UCLA: University of California, Los Angeles)H-Index: 41
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With the number of deaths due to stroke decreasing, more individuals are forced to live with crippling disability resulting from the stroke. To date, no therapeutics exist after the first 4.5 h after the stroke onset, aside from rest and physical therapy. Following stroke, a large influx of astrocytes and microglia releasing proinflammatory cytokines leads to dramatic inflammation and glial scar formation, affecting brain tissue's ability to repair itself. Pathological conditions, such as a stro...
#2Cynthia Nguyen(UCLA: University of California, Los Angeles)H-Index: 3
Last. S. Thomas Carmichael(UCLA: University of California, Los Angeles)H-Index: 48
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Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood–brain barrier and off-target effects. We tested a bioengineering approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel + BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate (Macaca fascicularis) and tracked with...
Preclinical studies have suggested that stem cell–based therapies possess the potential to improve stroke outcomes. Recently, the results of two early-stage clinical trials of stem cell therapy for chronic stroke have been published: the United Kingdom–based ReNeuron phase I clinical trial, called “Pilot Investigation of Stem Cells in Stroke” (PISCES, NCT01151124),1 and the United States–based SanBio phase I/IIa clinical trial, called “A Study of Modified Stem Cells in Stable Ischemic Stroke” (N...
Last. Tatiana Segura(UCLA: University of California, Los Angeles)H-Index: 41
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Stroke disability is the only major disease without an effective treatment. The substantial clinical burden of stroke in disabled survivors and the lack of a medical therapy that promotes recovery provide an opportunity to explore the use of biomaterials to promote brain repair after stroke. Hydrogels can be injected as a liquid and solidify in situ to form a gelatinous solid with similar mechanical properties to the brain. These biomaterials have been recently explored to generate pro-repair en...
Background and Purpose—Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes. Methods—Eighteen patients with stable, chronic stroke were enrolled in a 2-year, open-label, single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow–derived mesenchymal stem cells (SB623). Results—All patients in the safety population (N=18) experienced at least 1 treatment-emergent adverse event. Six patients experienc...
#1Paul Z. Elias(MIT: Massachusetts Institute of Technology)H-Index: 5
#2Myron Spector(Brigham and Women's Hospital)H-Index: 67
Injuries and diseases of the central nervous system (CNS) have the potential to cause permanent loss of brain parenchyma, with severe neurological consequences. Cavitary defects in the brain may afford the possibility of treatment with biomaterials that fill the lesion site while delivering therapeutic agents. This study examined the treatment of penetrating brain injury (PBI) in a rat model with collagen biomaterials and a soluble Nogo receptor (sNgR) molecule. sNgR was aimed at neutralizing my...
#1Jonathan Lam(UCLA: University of California, Los Angeles)H-Index: 7
#2William E. Lowry(UCLA: University of California, Los Angeles)H-Index: 33
Last. Tatiana Segura(UCLA: University of California, Los Angeles)H-Index: 41
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Stroke is the leading cause of adult disability with ~80% being ischemic. Stem cell transplantation has been shown to improve functional recovery. However, the overall survival and differentiation of these cells is still low. The infarct cavity is an ideal location for transplantation as it is directly adjacent to the highly plastic peri-infarct region. Direct transplantation of cells near the infarct cavity has resulted in low cell viability. Here we deliver neural progenitor cells derived from...
Last. John S. Forsythe(Monash University, Clayton campus)H-Index: 38
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Brain repair following disease and injury is very limited due to difficulties in recruiting and mobilizing stem cells towards the lesion. More importantly, there is a lack of structural and trophic support to maintain viability of the limited stem/progenitor cells present. This study investigates the effectiveness of an injectable gelatin-based hydrogel in attracting neural progenitor cells (NPCs) from the subventricular zone (SVZ) towards the implant. Glial cell-line-derived neurotrophic factor...
#1Guini Song(HUST: Huazhong University of Science and Technology)H-Index: 1
#2Min Zhao(HUST: Huazhong University of Science and Technology)H-Index: 1
Last. Yue He(HUST: Huazhong University of Science and Technology)
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Stroke has a high rate of morbidity and disability, which seriously endangers human health. In stroke, oxidative stress leads to further damage to the brain tissue. Therefore, treatment for oxidative stress is urgently needed. However, antioxidative drugs have demonstrated obvious protective effects in preclinical studies, but the clinical studies have not seen breakthroughs. Nanomaterials, with their characteristically small size, can be used to deliver drugs and have demonstrated excellent per...
Last. Adriano Aguzzi(UZH: University of Zurich)H-Index: 111
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Background and Purpose: The classic presentation of chronic (stage III) hemorrhagic stroke lesions is a fluid-filled cavity. In one of the most commonly used animal models of intracerebral hemorrha...
Although aging is a major risk factor for intracerebral hemorrhage (ICH), there are very few studies comparing ICH pathology between young and early middle-aged mice. In this study, 8-month old mice (early middle-aged mice) were compared against 2-month old mice (young mice) in neurological and histological changes after ICH induction, such as body weight, lesion volume, astrocytic responses, and motor and cognitive functions. At day 8 after ICH, there was no significant difference in lesion vol...
#1Pierre C. Dromel(MIT: Massachusetts Institute of Technology)H-Index: 1
#2Deepti Singh(MEE: Massachusetts Eye and Ear Infirmary)H-Index: 14
Last. Michael J. Young(MEE: Massachusetts Eye and Ear Infirmary)H-Index: 43
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Abstract Many progenitor and stem cell-based therapies in pre-clinical development and in clinical trial have failed to achieve desired outcomes, in part, due to: low cell viability; dispersion of cells from the injection site; and/or failure of the cells to differentiate and engraft into host tissue. These problems may be exacerbated by the elevated shear stress applied to the cells as they pass through a small-bore needle. Our supposition is that these issues can be mitigated by replacing the ...
Intracerebral hemorrhage (ICH) is a non-traumatic cerebrovascular disorder with very high morbidity and mortality and regarded as one of the deadliest stroke subtypes. Notably, there is no effective treatment for ICH. Despite an overall increase in preclinical studies, the pathophysiology of ICH is complex and remains enigmatic. To this end, ICH was induced in male CD-1 mice and the ipsilateral brain tissue was characterized in an unbiased manner using a combination of proteomics and bioinformat...