Cardiac Regeneration pp 295-305 | Cite as
Generation and Manipulation of Exosomes
- 2 Citations
- 1.2k Downloads
Abstract
Exosomes are membrane-bound nano-vehicles shed by most eukaryotic cells. Exosomes contain specific proteins and RNAs from parent cells, and they play key signaling roles in cellular development, modulation, and tissue regeneration. Attempts to isolate and modify exosomes to increase their targeting efficiency to specific tissue are still in their infancy. Here, we describe generation of exosomes from biopsy, isolation of exosomes by centrifugal ultrafiltration method, and approaches for manipulation of cardiac homing exosomes by chemical engineering for the treatment of myocardial infarction.
Key words
Exosome generation Exosome manipulation Myocardial infarction Cardiac homing peptide Platelet membrane Intravenous injectionNotes
Acknowledgments
This work was supported by grants from the National Institutes of Health to Dr. Ke Cheng (R01 HL123920, HL137093, HL144002, and HL146153) and the American Heart Association (18TPA34230092 and 19EIA34660286).
References
- 1.Momen-Heravi F, Balaj L, Alian S, Mantel PY, Halleck AE, Trachtenberg AJ, Soria CE, Oquin S, Bonebreak CM, Saracoglu E, Skog J, Kuo WP (2013) Current methods for the isolation of extracellular vesicles. Biol Chem 394(10):1253–1262. https://doi.org/10.1515/hsz-2013-0141CrossRefPubMedPubMedCentralGoogle Scholar
- 2.Vandergriff A, Huang K, Shen DL, Hu SQ, Hensley MT, Caranasos TG, Qian L, Cheng K (2018) Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide. Theranostics 8(7):1869–1878. https://doi.org/10.7150/thno.20524CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Boing AN, van der Pol E, Grootemaat AE, Coumans FA, Sturk A, Nieuwland R (2014) Single-step isolation of extracellular vesicles by size-exclusion chromatography. J Extracell Ves 3. https://doi.org/10.3402/jev.v3.23430
- 4.Koliha N, Wiencek Y, Heider U, Jungst C, Kladt N, Krauthauser S, Johnston IC, Bosio A, Schauss A, Wild S (2016) A novel multiplex bead-based platform highlights the diversity of extracellular vesicles. J Extracell Ves 5:29975. https://doi.org/10.3402/jev.v5.29975CrossRefGoogle Scholar
- 5.Martins TS, Catita J, Rosa IM, Silva OABDE, Henriques AG (2018) Exosome isolation from distinct biofluids using precipitation and column-based approaches. PLos One 13(6):e0198820. https://doi.org/10.1371/journal.pone.0198820CrossRefGoogle Scholar
- 6.Qiao L, Hu SQ, Liu SY, Zhang H, Ma H, Huang K, Li ZH, Su T, Vandergrif A, Tang JN, Allen T, Dinh PU, Cores J, Yin Q, Li YJ, Cheng K (2019) microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential. J Clin Invest 129(6):2237–2250. https://doi.org/10.1172/Jci123135CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Kanki S, Jaalouk DE, Lee S, Yu AYC, Gannon J, Lee RT (2011) Identification of targeting peptides for ischemic myocardium by in vivo phage display. J Mol Cell Cardiol 50(5):841–848. https://doi.org/10.1016/j.yjmcc.2011.02.003CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Won YW, McGinn AN, Lee M, Bull DA, Kim SW (2013) Targeted gene delivery to ischemic myocardium by homing peptide-guided polymeric carrier. Mol Pharm 10(1):378–385. https://doi.org/10.1021/mp300500yCrossRefPubMedGoogle Scholar
- 9.Su T, Huang K, Ma H, Liang H, Dinh P-U, Chen J, Shen D, Allen TA, Qiao L, Li Z, Hu S, Cores J, Frame BN, Young AT, Yin Q, Liu J, Qian L, Caranasos TG, Brudno Y, Ligler FS, Cheng K (2019) Platelet-inspired nanocells for targeted heart repair after ischemia/reperfusion injury. Adv Funct Mater 29(4):1803567. https://doi.org/10.1002/adfm.201803567CrossRefPubMedGoogle Scholar
- 10.Li ZH, Hu SQ, Cheng K (2018) Platelets and their biomimetics for regenerative medicine and cancer therapies. J Mater Chem B 6(45):7354–7365. https://doi.org/10.1039/c8tb02301h
- 11.Junnan T, Teng S, Ke H, Phuong-Uyen D, Zegen W, Adam V, Michael TH, Jhon C, Tyler A, Taosheng L, Erin S, Emily M, Leonard JL, Laura R, Alex L, Ashley B, Thomas GC, Deliang S, George AS, Zhen G, Jinying Z, Ke C (2018) Targeted repair of heart injury by stem cells fused with platelet nanovesicles. Nature Biomedical Engineering 2(1):17–26Google Scholar
- 12.Zhenhua L, Deliang S, Shiqi H, Teng S, Ke H, Feiran L, Lei H, Ke C (2018) Pretargeting and Bioorthogonal Click Chemistry-Mediated Endogenous Stem Cell Homing for Heart Repair. ACS Nano 12(12):12193–12200Google Scholar
- 13.Zhenhua L, Shiqi H, Ke H, Teng S, Jhon C, Ke C (2020) Targeted anti–IL-1β platelet microparticles for cardiac detoxing and repair. Science Advances 6(6):eaay0589Google Scholar
- 14.Deliang S, Zhenhua L, Shiqi H, Ke H, Teng S, Hongxia L, Feiran L, Ke C (2019) Antibody-Armed Platelets for the Regenerative Targeting of Endogenous Stem Cells. Nano Letters 19(3):1883–1891Google Scholar
- 15.Michael TH, James de A, Bruce K, Kathryn M, Junnan T, Zegen W, Thomas GC, Jorge P, Tao-Sheng L, Ke C (2015) Cardiac regenerative potential of cardiosphere-derived cells from adult dog hearts. Journal of Cellular and Molecular Medicine 19(8):1805–1813Google Scholar