Microvesicles from brain-extract-treated mesenchymal stem cells improve neurological functions in a rat model of
Ji Yong Lee1, Eiru Kim2, Seong-Mi Choi1
1Institute for BioMedical Convergence, Catholic Kwandong University-International St. Mary's Hospital, Incheon 22711, Republic of Korea.
Abstract:
Transplantation of mesenchymal stem cells (MSCs) was reported to improve functional outcomes in a rat model of ischemic stroke, and subsequent studies suggest that MSC-derived microvesicles (MVs) can replace the beneficial effects of MSCs. Here, we evaluated three different MSC-derived MVs, including MVs from untreated MSCs (MSC-MVs), MVs from MSCs treated with normal rat brain extract (NBE-MSC-MVs), and MVs from MSCs treated with stroke-injured rat brain extract (SBE-MSC-MVs), and tested their effects on ischemic brain injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. NBE-MSC-MVs and SBE-MSC-MVs had significantly greater efficacy than MSC-MVs for ameliorating ischemic brain injury with improved functional recovery. We found similar profiles of key signalling proteins in NBE-MSC-MVs and SBE-MSC-MVs, which account for their similar therapeutic efficacies. Immunohistochemical analyses suggest that brain-extract-treated MSC-MVs reduce inflammation, enhance angiogenesis, and increase endogenous neurogenesis in the rat brain. We performed mass spectrometry proteomic analyses and found that the total proteomes of brain-extract-treated MSC-MVs are highly enriched for known vesicular proteins. Notably, MSC-MV proteins upregulated by brain extracts tend to be modular for tissue repair pathways. We suggest that MSC-MV proteins stimulated by the brain microenvironment are paracrine effectors that enhance MSC therapy for stroke injury.
Insights
Mesenchymal stem cell-derived microvesicles (MVs) enhanced by brain extracts show improved therapeutic effects for ischemic stroke. These MVs promote tissue repair, reduce inflammation, and boost neurogenesis in rat models.
Area of Science:
- Regenerative Medicine
- Neuroscience
- Biotechnology
Background:
- Mesenchymal stem cells (MSCs) show therapeutic potential for ischemic stroke.
- MSC-derived microvesicles (MVs) may offer similar benefits to MSC transplantation.
- Optimizing MSC-MV composition could enhance stroke treatment efficacy.
Purpose of the Study:
- To evaluate the therapeutic effects of MSC-MVs treated with normal (NBE) and stroke-injured (SBE) rat brain extracts on ischemic stroke.
- To compare the efficacy of NBE-MSC-MVs and SBE-MSC-MVs against standard MSC-MVs.
- To elucidate the molecular mechanisms underlying the enhanced therapeutic effects of brain-extract-treated MSC-MVs.
Main Methods:
- Induction of permanent middle cerebral artery occlusion (pMCAO) in a rat model of ischemic stroke.
- Preparation and characterization of three types of MSC-MVs: MSC-MVs, NBE-MSC-MVs, and SBE-MSC-MVs.
- Assessment of functional recovery, immunohistochemical analysis, and mass spectrometry proteomic analysis.
Main Results:
- NBE-MSC-MVs and SBE-MSC-MVs demonstrated significantly greater efficacy in ameliorating ischemic brain injury and improving functional recovery compared to MSC-MVs.
- Similar signaling protein profiles were observed in NBE-MSC-MVs and SBE-MSC-MVs, correlating with their comparable therapeutic efficacies.
- Brain-extract-treated MSC-MVs were found to reduce inflammation, enhance angiogenesis, and promote endogenous neurogenesis in the injured brain.
Conclusions:
- MSC-MVs treated with brain extracts exhibit superior therapeutic potential for ischemic stroke compared to untreated MSC-MVs.
- The enhanced efficacy is attributed to specific protein enrichments in MVs, particularly those involved in tissue repair pathways.
- MSC-MV proteins stimulated by the brain microenvironment act as paracrine effectors, augmenting MSC therapy for stroke injury.
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