My long-term goal is to improve the recovery of stroke patients through basic and translational research of biological therapies like neural cell grafting. Because my background is in clinical research, my goal for the K08 award is to get the intensive basic science training and mentored research I need to build an R01-funded independent basic science lab that will lead to later translational studies of these exciting potential treatments. Research project: Post-stroke disability is a major public health problem. Intracerebral grafting of human neural progenitor cells is a promising potential therapy to improve recovery after stroke. Translating this treatment from the laboratory to clinical trials is challenged by the unfavorable environment for graft cell survival caused by structural disruption of brain tissue. Numerous materials termed scaffolds are available to provide structural support for graft cells, but few comparison data are available for selection.
In Aim 1, we will test the hypothesis that scaffolds with different molecular compositions may affect the survival or neural differentiation of human induced pluripotent cells in vitro. This data will allow better scaffold selection for subsequent grafting studies. Infarcted host tissue responses, including inflammation, astrocytosis, and angiogenesis, may also affect the fate of graft cells and scaffolds. Additionally, these graft-scaffold-host interactions may vary depending on the distance from the infarct.
In Aim 2, we will test the hypothesis that graft cells, scaffolds, and hst tissue respond to each other in spatially-dynamic ways that are important for graft and tissue outcomes in a rat lacunar stroke model. The therapeutic potential of graft-host neuronal synapses reconnecting an infarcted neural pathway may also be influenced by the grafting location relative to the damaged tract. A small, targeted infarct of the somatosensory thalamocortical tract, which occurs with the human stroke type termed thalamic lacune, provides an ideal model system to evaluate the effects of graft placements on tract reconnection.
In Aim 3, we will test the hypothesis that graft location will influence functional recovery of a rat mode of thalamic lacunar stroke through graft-host connectivity. Career development plan: My primary mentor will be stem cell neuroscientist Su-Chun Zhang, who will oversee the stem cell and neuroscience aspects of my research as well as my overall career development. I will also have one co-mentor each to focus specifically on the stroke science, the K08 physician-scientist aspects of my training, and my overall career development and training in the responsible conduct of research. I will supplement hands-on basic science training from mentors and consultants with coursework and extramural lab internships from leaders in the fields of cell therapy and brain injury recovery.

Public Health Relevance

The majority of stroke victims develop disability, which is a major public health problem with few effective treatments. I propose to study the use of gelling materials called scaffolds to support immature nervous system cells when they are transplanted into brain tissue injured by stroke, and to find the best way to place these cells and scaffolds in the brain to allow us to repair the damage caused by stroke. The knowledge gained by these studies may lead to new treatments to improve recovery for disabled stroke survivors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS079622-03
Application #
8847813
Study Section
NST-2 Subcommittee (NST)
Program Officer
Bosetti, Francesca
Project Start
2013-06-01
Project End
2016-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
3
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Neurology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Janik, Erika L; Jensen, Matthew B (2016) Every Man his own Electric Physician: T. Gale and the History of Do-It-Yourself Neurology. J Neurol Res Ther 1:17-22
Jensen, Matthew B; Jager, Lindsey D; Cohen, Laura K et al. (2016) Effects of neural differentiation maturity status of human induced pluripotent stem cells prior to grafting in a subcortical ischemic stroke model. Neurol Psychiatry Brain Res 22:178-182
Jensen, Matthew B; Janik, Erika L; Waclawik, Andrew J (2016) The Early Use of Blinding in Therapeutic Clinical Research of Neurological Disorders. J Neurol Res Ther 1:4-16
Jager, Lindsey D; Canda, Claire-Marie A; Hall, Crystal A et al. (2016) Effect of enzymatic and mechanical methods of dissociation on neural progenitor cells derived from induced pluripotent stem cells. Adv Med Sci 61:78-84
Heilingoetter, Cassandra L; Jensen, Matthew B (2016) Histological methods for ex vivo axon tracing: A systematic review. Neurol Res 38:561-9
Chang, Timothy S; Jensen, Matthew B (2015) Hemodilution for acute ischemic stroke. Stroke 46:e4-e5
Cohen, Laura K; Jensen, Matthew B (2015) Scaffolds for Intracerebral Grafting of Neural Progenitor Cells After Cerebral Infarction: A Systematic Review. Arch Neurosci 2:e25364
Chang, Timothy S; Jensen, Matthew B (2014) Haemodilution for acute ischaemic stroke. Cochrane Database Syst Rev :CD000103
Russek, Natanya S; Jensen, Matthew B (2014) Histological quantification of brain tissue inflammatory cell infiltration after focal cerebral infarction: a systematic review. Int J Neurosci 124:160-5
Mumtaz, Sehreen; Jensen, Matthew B (2014) Facial neuropathy with imaging enhancement of the facial nerve: a case report. Future Neurol 9:571-576

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