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Preconditioned Bone Marrow Derived Mesenchymal Stem Cells Reverse Ischemia Induced Neuronal Degeneration

Author(s)
Aisha Ishaque Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan:
Asmat Salim Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan:
Rida -e- Maria Qazi Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan:
Irfan Khan Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan:
Shabana U. Simjee Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan:
Durriyyah Sharifah Hasan Adli University of Malaya, Kuala Lumpur, Malaysia
Abstract
Pathologies of central nervous system are often associated with neuronal damage that worsen gradually and associated with loss of neuronal function. Regenerative medicine is an emerging field of biomedical science that exploits mesenchymal stem cells (MSCs) to regenerate the cells of neuronal lineage and treat neurodegenerative disorders effectively. To further improve regenerative capabilities of MSCs, preconditioning can be performed which improves their homing, survival, and migratory features. Current study deals with preconditioning of bone marrow MSCs using bioactive molecule (Alpha pinene; AP) for their differentiation towards neuronal lineage and to evaluate their regenerative potential in a rat model of cerebral ischemia. Rats were divided into normal control, diseased control, and normal and treated MSC transplanted groups. Ischemia was induced in adult rats by carotid artery ligation. Normal and treated MSCs were administered in their respective groups and brain tissues were harvested after one week of cell transplantation and assessed at histochemical, histopathological, and transcriptional levels. Histochemical analysis indicated the infarcted brain regions in diseased control compared to normal control group, whereas transplanted groups showed marked reduction in the infarcted area as compared to diseased group. Transcriptional profile of diseased control showed marked upregulation of HIF-1a and inflammatory mediators compared to normal control, while both transplanted groups showed reduced expression of these mediators. Histological analysis indicated neuronal damage, vascular edema, vacuolation, and distortion in the tissue architecture compared to normal control, whereas these damages were found to be reduced and reversed in the transplanted groups. The overall findings of the study demonstratres that bone marrow MSCs hold immense potential in their native as well as in preconditioned state to reverse neuronal damage induced in response to ischemic injury. Therefore, the current study provides a promising therapeutic approach against CNS anomalies due to neuronal loss.
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Published Journal: Abstract Book on 9th Annual Neuroscience Conference (ANC-23) August 12-13, 2023 , Volume: 0, Issue: 0, Year: 2023

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