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  3. Enhanced Therapeutic Effects of Mesenchymal Stem Cell-Derived Exosomes with an Injectable Hydrogel for Hindlimb Ischemia Treatment

Enhanced Therapeutic Effects of Mesenchymal Stem Cell-Derived Exosomes with an Injectable Hydrogel for Hindlimb Ischemia Treatment

  • ACS Appl Mater Interfaces. 2018 Sep 12;10(36):30081-30091. doi: 10.1021/acsami.8b08449.
Kaiyue Zhang,  Xiangnan Zhao,  Xiaoniao Chen,  Yongzhen Wei,  Wei Du,  Yuebing Wang,  Linan Liu 1,  Weian Zhao 1,  Zhibo Han 2 3,  Deling Kong,  Qiang Zhao,  Zhikun Guo 4,  Zhongchao Han 2,  Na Liu,  Fengxia Ma 3,  Zongjin Li
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, Department of Biomedical Engineering, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center & Edwards Lifesciences Center for Advanced Cardiovascular Technology, and Department of Biological Chemistry , University of California , Irvine 92697 , United States.
  • 2 Beijing Engineering Laboratory of Perinatal Stem Cells , Beijing Institute of Health and Stem Cells, Health & Biotech Co. , Beijing 100176 , China.
  • 3 State Key Lab of Experimental Hematology , Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020 , China.
  • 4 Henan Key Laboratory of Medical Tissue Regeneration , Xinxiang Medical University , Xinxiang 453003 , China.
PMID: 30118197 DOI: 10.1021/acsami.8b08449
Abstract

Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for cell-free treatment of various diseases. However, maintaining the retention and stability of exosomes over time in vivo after transplantation is a major challenge in the clinical application of MSC-derived exosomes. Here, we investigated if human placenta-derived MSC-derived exosomes incorporated with chitosan hydrogel could boost the retention and stability of exosomes and further enhance their therapeutic effects. Our results demonstrated that chitosan hydrogel notably increased the stability of proteins and MicroRNAs in exosomes, as well as augmented the retention of exosomes in vivo as confirmed by Gaussia luciferase imaging. In addition, we assessed endothelium-protective and proangiogenesis abilities of hydrogel-incorporated exosomes in vitro. Meanwhile, we evaluated the therapeutic function of hydrogel-incorporated exosomes in a murine model of hindlimb ischemia. Our data demonstrated that chitosan hydrogel could enhance the retention and stability of exosomes and further augment the therapeutic effects for hindlimb ischemia as revealed by firefly luciferase imaging of angiogenesis. The strategy used in this study may facilitate the development of easy and effective approaches for assessing and enhancing the therapeutic effects of stem cell-derived exosomes.

Keywords

cell-free therapy; chitosan hydrogel; exosomes; hindlimb ischemia; mesenchymal stem cell; molecular imaging.

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