MSC-Exos Promote Healing of MHs

Summary

Purpose: To assess the safety and efficacy of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) for promoting healing of large and refractory macular holes (MHs). Hypothesis: MSC and MSC-Exo therapy may promote functional and anatomic recovery from MH. MSC-Exo therapy may be a useful and safe method for improving visual outcomes of surgery for refractory MHs.

Timeline

Start

2017-03-01

Primary completion

2018-05-30

Completion

2021-12-30

Publications

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• Results Zhang L, Zheng H, Shao H, Nian H, Zhang Y, Bai L, Su C, Liu X, Dong L, Li X, Zhang X. Long-term therapeutic effects of mesenchymal stem cells compared to dexamethasone on recurrent experimental autoimmune uveitis of rats. Invest Ophthalmol Vis Sci. 2014 Aug 14;55(9):5561-71. doi: 10.1167/iovs.14-14788.
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• Results Machalinska A, Kawa M, Pius-Sadowska E, Stepniewski J, Nowak W, Roginska D, Kaczynska K, Baumert B, Wiszniewska B, Jozkowicz A, Dulak J, Machalinski B. Long-term neuroprotective effects of NT-4-engineered mesenchymal stem cells injected intravitreally in a mouse model of acute retinal injury. Invest Ophthalmol Vis Sci. 2013 Dec 23;54(13):8292-305. doi: 10.1167/iovs.13-12221.
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• Results Doeppner TR, Herz J, Gorgens A, Schlechter J, Ludwig AK, Radtke S, de Miroschedji K, Horn PA, Giebel B, Hermann DM. Extracellular Vesicles Improve Post-Stroke Neuroregeneration and Prevent Postischemic Immunosuppression. Stem Cells Transl Med. 2015 Oct;4(10):1131-43. doi: 10.5966/sctm.2015-0078. Epub 2015 Sep 3.
• Results Xin H, Li Y, Liu Z, Wang X, Shang X, Cui Y, Zhang ZG, Chopp M. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells. 2013 Dec;31(12):2737-46. doi: 10.1002/stem.1409.
• Results Katakowski M, Buller B, Zheng X, Lu Y, Rogers T, Osobamiro O, Shu W, Jiang F, Chopp M. Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett. 2013 Jul 10;335(1):201-4. doi: 10.1016/j.canlet.2013.02.019. Epub 2013 Feb 16.
• Results Xin H, Li Y, Buller B, Katakowski M, Zhang Y, Wang X, Shang X, Zhang ZG, Chopp M. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells. 2012 Jul;30(7):1556-64. doi: 10.1002/stem.1129.
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• Results Singh MS, Balmer J, Barnard AR, Aslam SA, Moralli D, Green CM, Barnea-Cramer A, Duncan I, MacLaren RE. Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion. Nat Commun. 2016 Nov 30;7:13537. doi: 10.1038/ncomms13537.
• Results Pearson RA, Gonzalez-Cordero A, West EL, Ribeiro JR, Aghaizu N, Goh D, Sampson RD, Georgiadis A, Waldron PV, Duran Y, Naeem A, Kloc M, Cristante E, Kruczek K, Warre-Cornish K, Sowden JC, Smith AJ, Ali RR. Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors. Nat Commun. 2016 Oct 4;7:13029. doi: 10.1038/ncomms13029.
• Results Yeo RW, Lai RC, Zhang B, Tan SS, Yin Y, Teh BJ, Lim SK. Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Adv Drug Deliv Rev. 2013 Mar;65(3):336-41. doi: 10.1016/j.addr.2012.07.001. Epub 2012 Jul 7.
• Results Bai L, Shao H, Wang H, Zhang Z, Su C, Dong L, Yu B, Chen X, Li X, Zhang X. Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Autoimmune Uveitis. Sci Rep. 2017 Jun 28;7(1):4323. doi: 10.1038/s41598-017-04559-y.
• Results Hillenkamp J, Kraus J, Framme C, Jackson TL, Roider J, Gabel VP, Sachs HG. Retreatment of full-thickness macular hole: predictive value of optical coherence tomography. Br J Ophthalmol. 2007 Nov;91(11):1445-9. doi: 10.1136/bjo.2007.115642. Epub 2007 May 2.
• Results Xin H, Li Y, Chopp M. Exosomes/miRNAs as mediating cell-based therapy of stroke. Front Cell Neurosci. 2014 Nov 10;8:377. doi: 10.3389/fncel.2014.00377. eCollection 2014.

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