Efficacy of Transplant and Endogenous Precursor and Stem Cell Interventions on Stroke Recovery: A Critical Assessment

2012 ◽  
pp. 47-61
Author(s):  
Dale Corbett ◽  
Cindi Morshead ◽  
Molly Shoichet
Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Gourav Choudhury ◽  
Marcel Daadi

Ischemic stroke is the leading cause of upper extremity motor impairments. Well-characterized experimental stroke models for upper extremity motor impairment remain underdeveloped. Cortical representation of dexterous movements in nonhuman primates (NHP) is functionally and topographically similar to that in humans. We recently reported the characterization of an NHP model of focal ischemia reperfusion with a defined syndrome, impaired arm function and finger dexterity. In this study, we investigated the cellular changes in the neural stem cell compartment and glial cell populations in this NHP model. NHPs were subjected to transient cerebral ischemia by temporarily occluding the M3 segment of the left side middle cerebral artery (MCA). Motor and cognitive functions following the stroke were evaluated using the object retrieval task with barrier-detour. Postmortem analysis included magnetic resonance imaging (MRI) and immunohistopathology to map the infarct and characterize the neurogenic and gliogenic changes. The MCA occlusion produced significant loss of fine motor function characterized by impaired dexterity. Immunocytochemical analysis revealed significant increase of Sox2+ neural stem cells in the subventricular zone, and of GFAP+ astrocytes (P<0.0001) and Iba-1+ microglia (P<0.0001) in the infarct region. In addition, there was a 42% increase in doublecortin positive cells (P<0.0001) compared to non-ischemic hemisphere. This study describes the cellular composition of the endogenous changes in the neural stem cell compartment and in the stroke region. These data may help reveal the cellular identity mediating neural plasticity and the cellular mechanisms mediating behavioral deficits and post-stroke recovery.


2019 ◽  
Vol 29 (24) ◽  
pp. 1900603 ◽  
Author(s):  
Tianyuan Zhang ◽  
Fangyuan Li ◽  
Qianhao Xu ◽  
Qiyue Wang ◽  
Xinchi Jiang ◽  
...  

2019 ◽  
Vol 33 (2) ◽  
Author(s):  
Avigdor Leftin ◽  
Jens T. Rosenberg ◽  
Xuegang Yuan ◽  
Teng Ma ◽  
Samuel C. Grant ◽  
...  

2016 ◽  
Vol 36 (41) ◽  
pp. 10529-10544 ◽  
Author(s):  
M. Bacigaluppi ◽  
G. L. Russo ◽  
L. Peruzzotti-Jametti ◽  
S. Rossi ◽  
S. Sandrone ◽  
...  

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Kelly M Scheulin ◽  
Brian J Jurgielewicz ◽  
Monika Saini ◽  
Samantha E Spellicy ◽  
Elizabeth S Waters ◽  
...  

Despite the devastating global impact of ischemic stroke, there are few Food and Drug Administration (FDA) approved treatments, none of which are capable of regenerating or replacing infarcted brain tissue. Recently, our group demonstrated that induced pluripotent stem cell derived neural stem cells (iNSCs) are a regenerative and neuroprotective cell replacement therapy in an ischemic stroke porcine model that closely resembles human stroke pathophysiology. Historically, intracerebral stem cell transplantations have been largely guided by the injury site without taking individual neuroanatomical structures and their functions into consideration. Utilizing magnetic resonance imaging (MRI), the current study aims to identify key structures lesioned by a permanent middle cerebral artery occlusion (MCAO) that impact stroke recovery in a preclinical porcine model and determine an ideal transplantation location for future stroke iNSC transplant studies. A porcine MRI brain atlas was registered to identify stroke lesion location, and linear regressions between infarcted brain structures and functional data were completed to evaluate the predictive capacity of individual brain structure lesion on neurological outcome. MCAO resulted in prominent lesion volumes and decreased white matter integrity. Highly lesioned brain structures included the insular cortex, somatosensory cortices, visual cortices, temporal gyri, and putamen. MCAO severely impaired translational gait parameters, decreased voluntary movement in open field testing, and resulted in increased modified Rankin Scale (mRS) scoring. Linear regression analysis determined that lesions in the secondary visual cortex, claustrum, amygdala, and superior temporal gyrus were highly prognostic of overall gait and behavioral outcomes. This regression analysis approach identified neuroanatomical structures that were predictive of stroke outcome, and these structures may be key iNSC transplantation locations to facilitate optimal functional recovery.


2020 ◽  
Vol 21 (8) ◽  
pp. 781-791
Author(s):  
Samira Asgharzade ◽  
Andisheh Talaei ◽  
Tahereh Farkhondeh ◽  
Fatemeh Forouzanfar

Stroke is a serious, life-threatening condition demanding vigorous search for new therapies. Recent research has focused on stem cell-based therapies as a viable choice following ischemic stroke, based on studies displaying that stem cells transplanted to the brain not only survive but also cause functional recovery. Growth factors defined as polypeptides that regulate the growth and differentiation of many cell types. Many studies have demonstrated that combined use of growth factors may increase results by the stimulation of endogenous neurogenesis, anti-inflammatory, neuroprotection properties, and enhancement of stem cell survival rates and so may be more effective than a single stem cell therapy. This paper reviews and discusses the most promising new stroke recovery research, including combination treatment.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Solomon O. Ugoya ◽  
Jian Tu

Traumatic brain injury (TBI) is one of the leading causes of major disability and death worldwide. Neural stem cells (NSCs) have recently been shown to contribute to the cellular remodelling that occurs following TBI and attention has been drawn to the area of neural stem cell as possible therapy for TBI. The NSCs may play an important role in the treatment of TBI by replacing the damaged cells and eventual remyelination. This paper summarized a critical assessment of recent data and developed a view comprising of six points to possible quality translation of NSCs in TBI.


2010 ◽  
Vol 24 (7) ◽  
pp. 636-644 ◽  
Author(s):  
Jin Zhong ◽  
Albert Chan ◽  
Leeron Morad ◽  
Harley I. Kornblum ◽  
Guoping Fan ◽  
...  

Stroke is a leading cause of adult disability. Stem/progenitor cell transplantation improves recovery after stroke in rodent models. These studies have 2 main limitations to clinical translation. First, most of the cells in stem/progenitor transplants die after brain transplantation. Second, intraparenchymal approaches target transplants to normal brain adjacent to the stroke, which is the site of the most extensive natural recovery in humans. Transplantation may damage this tissue. The stroke cavity provides an ideal target for transplantation because it is a compartmentalized region of necrosis, can accept a high volume transplant without tissue damage, and lies directly adjacent to the most plastic brain area in stroke. However, direct transplantation into the stroke cavity has caused massive death in the transplant. To overcome these limitations, the authors tested stem/progenitor transplants within a specific biopolymer hydrogel matrix to create a favorable environment for transplantation into the infarct cavity after stroke, and they tested this in comparison to stem cell injection without hydrogel support. A biopolymer hydrogel composed of cross-linked hyaluronan and heparin sulfate significantly promoted the survival of 2 different neural progenitor cell lines in vitro in conditions of stress and in vivo into the infarct cavity. Quantitative analysis of the transplant and surrounding tissue indicates diminished inflammatory infiltration of the graft with the hydrogel transplant. This result indicates that altering the local environment in stem cell transplantation enhances survival and diminishes cell stress. Stem cell transplantation into the infarct cavity within a pro-survival hydrogel matrix may provide a translational therapy for stroke recovery.


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