Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis

Venugopal, Chaitra and Christopher, Shamir and Senthilkumar, Sivapriya and Babu, Janitri Venkatachala and Sonu, Peedikayil Kurien and Nishtha, Kusum Jain and Rai, Kiranmai S and Shobha, K and Dhanushkodi, Anandh (2017) Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis. Current Gene Therapy, 17 (5). pp. 379-390.

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Abstract

Background: Neurodegenerative diseases comprise a group of disorders for which no treatment is available till date. Stem cell based therapy offers great hope and promise. However, stem cell transplantation is associated with certain disadvantages like poor targeted migration, engraftment and survival of the transplanted cells.Material & Method: Exosomes, a type of extracellular membrane vesicle released by all cell types including stem cells, offer an alternative to stem cell transplantation. Exosome carry a wide array of biomolecules and are implicated in exhibiting substantial benefits in the repair/regeneration of the injured tissue. Thus, exosomes offer an alternative therapeutic approach as a substitute of cell transplantation. In order to utilize exosomes for therapeutic purpose, it is essential to evaluate the appropriate passage number and the dosage to avoid possible cytotoxic effects. Here, we isolated exosomes from different passages of rat bone marrow mesenchymal stem cells (BM-MSC) and analysed the neuroprotective potential of BM-MSC exosomes in an in vitro model of excitotoxicity.Result: Our results demonstrated that the exosomes isolated from early passage of rat BM-MSC exhibited more efficient neuroprotective potential as opposed to later passages derived exosomes. Furthermore, the neuroprotective efficacy of exosome is dosage dependent. i.e. the lower dosage of exosomes was found to be neuroprotective, whereas higher dosage of exosomes (from later passages) was found to be detrimental to neurons. The early passage derived exosomes protected neurons through anti-apoptotic, anti-necrotic and anti-oxidant mechanisms.Conclusion: Our study suggests that adult stem cells derived exosomes could be a potential therapeutic agent to confer neuroprotection in neurodegenerative diseases like Alzheimer's disease

Item Type: Article
Uncontrolled Keywords: Hippocampus; Bone marrow; Mesenchymal; Exosomes; Neurodegeneration; Neuroprotection
Subjects: Medicine > MMMC Manipal > Physiology
Regenerative Medicine > MIRM Bangalore
Depositing User: KMC Library
Date Deposited: 14 Mar 2018 10:32
Last Modified: 14 Mar 2018 10:32
URI: http://eprints.manipal.edu/id/eprint/150775

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