A systematic review of preclinical studies on the therapeutic potential of mesenchymal stromal cell-derived microvesicles.

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.

Impact of ethnicity on human umbilical cord blood banking: a systematic review.

BACKGROUND: How ethnicity impacts characteristics of umbilical cord blood collected by cord blood banks remains unclear. STUDY DESIGN AND METHODS: After a systematic search, we identified 11 studies for analysis that reported on various variables of collected cord blood units. RESULTS: Non-Caucasian ethnicity of the cord blood donor was associated with a higher risk of failing to meet banking criteria, lower cord blood volume, reduced total nucleated cell count, fewer CD34+ cells, and reduced colony-forming units. CONCLUSIONS: Non-Caucasian ethnicity is associated with reductions in hematopoietic measures of collected cord blood units. Public banking efforts will have to balance issues related to building ethnic diversity within the bank and maintaining the characteristics of banked units that remain desirable by transplant centers.