title: Safety evaluation of exosomes derived from human umbilical cord mesenchymal stromal cell.
abstract: OBJECTIVE
  Mounting evidence shows that non-cell-based transplantation of exosomes derived from mesenchymal stromal cells (MSCs) has more potential protective and reparative effects than MSCs have. However, whether it is safe to transplant MSC exosomes into tissues is still not clear. In this study, we evaluated the safety of transplantation of exosomes derived from human umbilical cord MSCs (hucMSC exosomes).
  
  
  METHODS
  hucMSC exosomes were incubated with the cardiac blood from a healthy rabbit, and hemolysis was observed. For analysis of vascular and muscle stimulation, pyrogen, systemic anaphylaxis and hematology indexes, hucMSC exosomes were given to rabbits, guinea pigs and rats. The histological changes in the vascular and muscle sites of injection in rabbits were analyzed by hematoxylin and eosin staining. Allergy symptoms in guinea pigs and rectal temperature of rabbits were observed and recorded. To study safety in vivo, hucMSC exosomes were infused intravenously into rats with acute myocardial infarction. Rats' weight was measured and tail vein blood was collected to evaluate liver and renal function.
  
  
  RESULTS
  hucMSC exosomes had a protective effect on weight loss and had no adverse effects on liver or renal function. Other detections, such as hemolysis, vascular and muscle stimulation, systemic anaphylaxis, pyrogen and hematology indexes, also showed that hucMSC exosomes were applicable.
  
  
  CONCLUSIONS
  hucMSC exosomes are well tolerated in animal models. This study provides evidence for the safety of intravenous infusion in future clinical therapy.
authors: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
authors: Li
authors: L
authors: Sun
authors: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
authors: Rongman
authors: R
authors: Xu
authors: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
authors: Xiaoxian
authors: X
authors: Sun
authors: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
authors: Yuping
authors: Y
authors: Duan
authors: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
authors: Yiwen
authors: Y
authors: Han
authors: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
authors: Yuanyuan
authors: Y
authors: Zhao
authors: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
authors: Hui
authors: H
authors: Qian
authors: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China; The Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu, China. Electronic address: zhuwei@ujs.edu.cn.
authors: Wei
authors: W
authors: Zhu
authors: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China; The Affiliated Hospital, Jiangsu University, Zhenjiang, Jiangsu, China. Electronic address: icls@ujs.edu.cn.
authors: Wenrong
authors: W
authors: Xu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D055354:Exosomes / Q000637:transplantation*; D005260:Female; D006168:Guinea Pigs; D006461:Hemolysis; D006801:Humans; D008099:Liver / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000648:ultrastructure*; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014470:Umbilical Cord / Q000166:cytology*
keywords: exosomes; human umbilical cord; mesenchymal stromal cell; safety