CONTACT US: Contact info
|
Citation |
Mishra SK, Rana P, Khushu S, Gangenahalli G. Stem Cells Transl. Med. 2016; ePub(ePub): ePub. |
|
Affiliation |
Division of Stem Cell and Gene Therapy Research, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Timarpur, Delhi, India skhushu@yahoo.com gugdutta@rediffmail.com. |
|
Copyright |
(Copyright © 2016, AlphaMed Press) |
|
DOI |
|
PMID |
27502517 |
|
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. SIGNIFICANCE: Traumatic brain injury (TBI) is a unique kind of injury and its treatment is a complex clinical issue. An insult to brain directly affects the gene expression profile for protein synthesis and eventually affects metabolic levels. This study provided a detailed description of the effects after homing of stem cells to the lesion area by administering fluorescent-labeled mesenchymal stem cells (MSCs) and then performing analysis using fluorescent microscopy and serial in vivo proton magnetic resonance spectroscopy using a 7.0 Tesla magnetic resonance imaging (MRI) scanner. After injury, the affected profile of neurometabolites at an injury site, and the neurometabolite profile's subsequent restoration to normal levels detected in the study after stem cell transplantation, revealed a pattern. It was proposed that this likely was a recovery signature (bio-indicator) of TBI after stem cell therapy. This study was the first to report on the patterned recovery of altered neurometabolites after transplantation of MSCs in a TBI mice model, which possibly occurred as a regenerative response. Behavioral studies conducted simultaneously have also been well-correlated with MRI findings. Language: en |