Stem Cell Reviews and Reports

, Volume 11, Issue 1, pp 150–160

A Systematic Review of Preclinical Studies on the Therapeutic Potential of Mesenchymal Stromal Cell-Derived Microvesicles

  • Celine Akyurekli
  • Yevgeniya Le
  • Richard B. Richardson
  • Dean Fergusson
  • Jason Tay
  • David S. Allan
Article

DOI: 10.1007/s12015-014-9545-9

Cite this article as:
Akyurekli, C., Le, Y., Richardson, R.B. et al. Stem Cell Rev and Rep (2015) 11: 150. doi:10.1007/s12015-014-9545-9

Abstract

Background

The therapeutic potential of mesenchymal stromal cells (MSCs) may be largely mediated by paracrine factors contained in microvesicles (MV) released from intracellular endosomes. A systematic review of controlled interventional animal studies was performed to identify models of organ injury where clinical translation of MSC-derived microvesicle therapy appears most promising as regenerative therapy.

Methods

A total of 190 published articles were identified in our systematic search of electronic databases (MEDLINE, EMBASE, PUBMED). After screening for eligibility, a total of 17 controlled studies testing MSC-derived MVs as therapeutic interventions in animal models of disease underwent comprehensive review, quality assessment, and data extraction.

Results

Thirteen studies addressed the regenerative potential following organ injury. Six studies were included on acute kidney injury, 4 on myocardial infarction and reperfusion injury, 1 on hind limb ischemia, 1 on liver injury, and 1 on hypoxic lung injury. Four studies addressed immunological effects of MSC-derived MVs on inhibiting tumor growth. Twelve studies (71 %) provided explicit information regarding the number of animals allocated to treatment or control groups. Five studies (29 %) randomly assigned animals to treatment or control groups and only 1 study (6 %) reported on blinding. Therapeutic intervention involved isolation of exosomes (40–100 nm) in eight studies, while nine studies tested unfractionated microvesicles (<1,000 nm). In studies of tissue regeneration, all 13 reported that treatment with MSC-derived MVs improved at least one major/clinical parameter associated with organ dysfunction. Three of 4 studies evaluating the inhibition of tumor growth reported benefit.

Conclusions

In preclinical studies, the use of MSC-derived MVs is strongly associated with improved organ function following injury and may be useful for inhibiting tumor growth. Improved preclinical study quality in terms of treatment allocation reporting, randomization and blinding will accelerate needed progress towards clinical trials that should assess feasibility and safety of this therapeutic approach in humans.

Keywords

Mesenchymal stromal cellsMicrovesiclesExosomesPreclinicalAnimal modelsSystematic review

Copyright information

© Crown Copyright as represented by: Atomic Energy of Canada Limited 2014

Authors and Affiliations

  • Celine Akyurekli
    • 1
  • Yevgeniya Le
    • 1
    • 4
  • Richard B. Richardson
    • 4
  • Dean Fergusson
    • 2
  • Jason Tay
    • 2
    • 3
  • David S. Allan
    • 1
    • 3
    • 5
  1. 1.Regenerative Medicine ProgramOttawa Hospital Research InstituteOttawaCanada
  2. 2.Clinical Epidemiology ProgramOttawa Hospital Research InstituteOttawaCanada
  3. 3.Department of Medicine, HematologyUniversity of OttawaOttawaCanada
  4. 4.Atomic Energy of Canada LimitedOttawaCanada
  5. 5.Ottawa Hospital Research InstituteOttawaCanada