Stem Cell Research

Traumatic injuries lead to significant morbidity and mortality, particularly among children, adolescents, and young adults.  More specifically, traumatic brain injury (TBI) contributes to half of all trauma-related deaths and frequent, devastating prolonged morbidity, imposing a huge economic impact on individuals and society.  There is no current treatment to reverse the cellular destruction associated with TBI.  Cellular therapy is a burgeoning field of experimental treatment that has shown promise in the management of many diseases, including TBI.  The overarching objective of our clinical, translational, and basic science program is to explore the therapeutic potential of cellular therapy for traumatic brain injury.

We use a controlled cortical impact (CCI) injury rat model of TBI.  After cellular injection, the rats are tested for improvements in motor and cognitive function.  Cellular changes in the rat brain are then identified through magnetic resonance imaging and immunohistochemistry.  We have the ability to isolate and characterize various stem and progenitor cell populations, including rat mononuclear cells (rMNC), rat mesenchymal stem cells (rMSC), rat hematopoietic stem cells (rHSC), and rat multipotent adult progenitor cells (rMAPC).  In addition, we collaborate with other labs to obtain rat neural stem cells (rNSC) and human mesenchymal stem cells (hMSC).

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Subacute rNSC therapy for TBI

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Rat Mesenchymal Stem Cells
Detailed Immunophenotype characterization

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I.V. MSC Therapy for TBI

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Proinflammatory state
Examination of the acute, local proinflammatory state after TBI

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MSC’s from GFP+transgenic rodents
Investigation of the limitations of isolation and expansion

We have numerous specific areas of ongoing investigation.  Overall, we hope to gain insight into the therapeutic potential of the various stem cell populations mentioned above.  In addition, we hope to better characterize the optimal route(s) of administration, as well as optimal cell number.  More specifically, given the increasing evidence that cellular death continues over a significant period of time, we are studying delayed cellular therapies for TBI.  Most traumatically injured patients suffer concomitant injuries, so we will study the differential migration of cells to various organs in a “poly-trauma” model (combining TBI with hemorrhagic shock, pulmonary contusion, etc).  In order to increase our understanding of processes at the cellular level, we will continue to better characterize our cells through flow cytometry and immunocytology.  We also study the microenvironment interactions between transplanted and native cells, including co-culture work and incubation of cells with TBI extract.

– Charles S. Cox Jr. MD