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.

Scientific Reports
|September 10, 2016
PubMed

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.