Stroke repair with cell transplantation: neuronal cells, neuroprogenitor cells, and stem cells

Kondziolka, Douglas; Wechsler, Lawrence R.

doi:10.3171/foc/2008/24/3-4/e12

Cited by 28 publications

(13 citation statements)

References 33 publications

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“…Cells were implanted via stereotaxic-guided injection into the basal ganglia of stroke patients. Postrecovery functional/neurological assessments demonstrated trending improvements but were statistical insignificant [208]. …”

Section: Suppression Of Epha4 Activationmentioning

confidence: 83%

Models of CNS injury in the nonhuman primate: A new era for treatment strategies

Teo

Rosenfeld²,

Bourne

2012

Translational Neuroscience

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Central nervous system (CNS) injuries affect all levels of society indiscriminately, resulting in functional and behavioral deficits with devastating impacts on life expectancies, physical and emotional wellbeing. Considerable literature exists describing the pathophysiology of CNS injuries as well as the cellular and molecular factors that inhibit regrowth and regeneration of damaged connections. Based on these data, numerous therapeutic strategies targeting the various factors of repair inhibition have been proposed and on-going assessment has demonstrated some promising results in the laboratory environ. However, several of these treatment strategies have subsequently been taken into clinical trials but demonstrated little to no improvement in patient outcomes. As a result, options for clinical interventions following CNS injuries remain limited and effective restorative treatment strategies do not as yet exist. This review discusses some of the current animal models, with focus on nonhuman primates, which are currently being modeled in the laboratory for the study of CNS injuries. Last, we review the current understanding of the mechanisms underlying repair/regrowth inhibition and the current trends in experimental treatment strategies that are being assessed for potential translation to clinical applications.

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Section: Suppression Of Epha4 Activationmentioning

confidence: 83%

Models of CNS injury in the nonhuman primate: A new era for treatment strategies

Teo

Rosenfeld²,

Bourne

2012

Translational Neuroscience

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“…The potential of tissue regenerative therapy based on stem cell transplantation has been demonstrated for a number of ailments including heart disease [4], neurodegenerative disorders such as Parkinson’s disease [32] and Alzheimer’s dementia [21], ophthalmologic disorders [16], and diabetes [26] among others [7, 17, 19]. It is known that factors such as SDF-1/CXCR4 [22] and BMP receptor type IA [33] govern stem cell migration, adhesion and engraftment; however, the in vivo integration of the transplanted stem cells into host parenchyma has been difficult to assess because they cannot be distinguished based on their morphological properties.…”

Section: Introductionmentioning

confidence: 99%

Targeting aldehyde dehydrogenase: a potential approach for cell labeling

Vaidyanathan

Song

Affleck

et al. 2009

Nuclear Medicine and Biology

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Introduction-To advance the science and clinical application of stem cell therapy, the availability of a highly sensitive, quantitative, and translational method for tracking stem cells would be invaluable. Because hematopoetic stem cells express high levels of the cytosolic enzyme aldehyde dehydrogenase-1A1 (ALDH1), we sought to develop an agent that is specific to ALDH1 and thus to cells expressing the enzyme. Such an agent might be also helpful in identifying tumors that are resistant to cyclophosphomide chemotherapy because ALDH1 is known to be responsible for this resistance. Results-The average radiochemical yields for the synthesis [ 125 I]FMIC and [ 125 I]DEIBA were 70 ± 5% and 47 ± 14%, respectively. ALDH1 converted both compounds to respective acids suggesting their suitability as ALDH1 imaging agents. Although ability of ALDH1 within the cells to oxidize one of these substrates was shown, specific uptake in ALDH-expressing tumor cells could not be demonstrated. Methods-WeConclusion-To pursue this approach for ALDH1 imaging, radiolabeled aldehydes need to be designed such that, in addition to being good substrates for ALDH1, the cognate products should be sufficiently polar so as to be retained within the cells.

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“…The adult mammalian hippocampus is a resident to neural progenitor cells, and experimental brain injuries, such as ischemia, in rodents have been shown to promote endogenous neurogenesis in the dentate gyrus, DG) and CA1 region (Gage et al 1998; Nakatoma et al, 2002). Neurogenesis has been implicated as a robust endogenous repair mechanism, and equally a potential target for cell therapy (Guzman et al, 2008; Hara et al, 2008; Hess and Borlongan, 2008; Kondziolka and Wechsler, 2008; Kondziolka et al, 2000; Kondziolka et al, 2005), as well as neuroprotective and neurorestorative drugs, thereby soliciting investigations into this cell survival pathway as a strategy for treating ischemic injury.…”

Section: Introductionmentioning

confidence: 99%

Anomaly in aortic arch alters pathological outcome of transient global ischemia in Rhesus macaques

et al. 2009

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We investigated a non-human primate (NHP) transient global ischemia (TGI) model which was induced by clipping the arteries originating from the aortic arch. Previously we demonstrated that our TGI model in adult Rhesus macaques (Macaca mulatta) results in marked neuronal cell loss in the hippocampal region, specifically the cornu Ammonis (CA1) region. However, we observed varying degrees of hippocampal cell loss among animals. Here, we report for the first time an anomaly of the aortic arch in some Rhesus macaques that appears as a key surgical factor in ensuring the success of the TGI model in this particular NHP. Eleven adult Rhesus macaques underwent the TGI surgery, which involved 10-15-minute clipping of both innominate and subclavian arteries. Animals were allowed to survive between 1 day and 28 days after TGI. Because of our experience and knowledge that Japanese macaques exhibited only innominate and subclavian arteries arising from the aortic arch, macroscopic visualization of these two arteries alone in the Rhesus macaques initially assured us that clipping both arteries was sufficient to produce TGI. During the course of one TGI operation, however, we detected 3 arterial branches arising from the aortic arch, which prompted us to subsequently search for 3 branches in succeeding TGI surgeries. In addition, we performed postmortem examination of the heart to confirm the number of arterial branches in the aortic arch. Finally, in order to reveal the pathological effect of the aortic arch anomaly, we compared the hippocampal cell loss between animals found to have 3 arterial branches but had all or only two branches clipped during TGI operation. Post-mortem examination revealed eight NHPs had the typical two arterial aortic branches, but three NHPs displayed an extra arterial aortic branch, indicating that about 30% of Rhesus macaques had 3 arterial branches arising from the aorta. Histological analyses using Nissl staining showed that in NHPs with the aortic arch anomaly clipping only two of three arterial branches led to a partial cell loss and minimal alteration in number of cell layers in the hippocampal region *Address correspondence to: Department of Neurosurgery, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612; cborlong@health.usf.edu; Tel: 813-974-1377; Fax: 813-974-1364. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. when compared with clipping all three branches, with the hippocampal cell death in the latter resembling the pathological outcome achieved by clipping the two arterial branches in NHPs disp...

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Stroke repair with cell transplantation: neuronal cells, neuroprogenitor cells, and stem cells

Cited by 28 publications

References 33 publications

Models of CNS injury in the nonhuman primate: A new era for treatment strategies

Models of CNS injury in the nonhuman primate: A new era for treatment strategies

Targeting aldehyde dehydrogenase: a potential approach for cell labeling

Anomaly in aortic arch alters pathological outcome of transient global ischemia in Rhesus macaques

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