Abstract
Improved therapeutic assessment of experimental traumatic brain injury (TBI), using mesenchymal stem cells (MSCs), would immensely benefit its therapeutic management. Neurometabolite patterns at injury site, measured with proton magnetic resonance spectroscopy (1H‐MRS) after MSCs transplantation, may serve as a bio‐indicator of the recovery mechanism. This study used in vivo magnetic resonance imaging and 1H‐MRS to evaluate the therapeutic prospects of implanted MSCs at injury site in experimental mice longitudinally up to 21 days. Negative tissue contrast and cytotoxic edema formation were observed in susceptibility‐based contrast (T2*) and an apparent diffusion coefficient map, respectively. Lesion site showed decreased N‐acetylaspartate, total choline, myo‐inositol, total creatine, glutamate‐glutamine complex, and taurine neurometabolic concentrations by 1H‐MRS investigation. There was a considerable decrease in locomotor activity, depression index, and cognitive index after TBI. It may, therefore, be inferred that MSC transplantation prompted recovery by decreasing negative signals and edema, restoring metabolites to baseline concentrations, and enhancing behavioral activity. Overall findings support the potential of MSC transplantation for the enhancement of endogenous neuroprotective responses, which may provide future clinical applications for translating laboratory research into therapeutic clinical advances. Stem Cells Translational Medicine 2017;6:316–329
Highlights
Traumatic brain injury (TBI) is a major universal cause of a broad range of physical, cognitive, behavioral, and emotional disabilities, depending on the type, severity, and location of injury [1]
Immunocytochemistry results showed that the surface antigens of the isolated stem cells tested positive for mesenchymal cells (Sca-1 and CD90.2) and negative for hematopoietic lineages (CD34 and CD45), and they showed low expression for macrophages (CD-11b) antigen (Fig. 2A–2E)
Cellular morphology exhibited a change after culturing in osteoinductive medium and adipogenic medium (Fig. 2F, 2G)
Summary
Traumatic brain injury (TBI) is a major universal cause of a broad range of physical, cognitive, behavioral, and emotional disabilities, depending on the type, severity, and location of injury [1]. There has been no development of clinical therapeutics to effectively interrupt secondary brain injury [4], which occurs progressively in the period following the initial trauma. Stem cell transplantation offers promising therapeutic potential for various tissue injuries [5]. Mesenchymal stem cells (MSCs) are multipotent in nature and have the capacity to differentiate themselves into various mesodermal tissue lineages depending on the microenvironment and signaling processes [9]. In addition to their immune regulatory behavior, their paracrine mechanisms involving the release of trophic and immunomodulatory factors [10] would determine the manner in which MSCs are used. Cell-based treatment of acute TBI is clinically realistic and could facilitate the smooth progress of functional improvement [8, 13]
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