Dead Mesenchymal Stem Cells for Radiation Lung Injury

Summary

The aim of this single center, single arm and prospective study is to explore the safety and efficacy of hDMSCs in the treatment of radiation pneumonitis.

Timeline

Start

2023-09-10

Primary completion

2024-09-10

Completion

2024-09-30

Publications

• Background Alfouzan AF. Radiation therapy in head and neck cancer. Saudi Med J. 2021 Mar;42(3):247-254. doi: 10.15537/smj.2021.42.3.20210660.
• Background Bracci S, Valeriani M, Agolli L, De Sanctis V, Maurizi Enrici R, Osti MF. Renin-Angiotensin System Inhibitors Might Help to Reduce the Development of Symptomatic Radiation Pneumonitis After Stereotactic Body Radiotherapy for Lung Cancer. Clin Lung Cancer. 2016 May;17(3):189-97. doi: 10.1016/j.cllc.2015.08.007. Epub 2015 Aug 29.
• Background Giuranno L, Ient J, De Ruysscher D, Vooijs MA. Radiation-Induced Lung Injury (RILI). Front Oncol. 2019 Sep 6;9:877. doi: 10.3389/fonc.2019.00877. eCollection 2019.
• Background Chun SG, Hu C, Choy H, Komaki RU, Timmerman RD, Schild SE, Bogart JA, Dobelbower MC, Bosch W, Galvin JM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Raben A, Augspurger ME, MacRae RM, Paulus R, Bradley JD. Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial. J Clin Oncol. 2017 Jan;35(1):56-62. doi: 10.1200/JCO.2016.69.1378. Epub 2016 Oct 31.
• Background Madan R, Benson R, Sharma DN, Julka PK, Rath GK. Radiation induced heart disease: Pathogenesis, management and review literature. J Egypt Natl Canc Inst. 2015 Dec;27(4):187-93. doi: 10.1016/j.jnci.2015.07.005. Epub 2015 Aug 18.
• Background Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, Schellenberg D, Ahmad B, Senthi S, Swaminath A, Kopek N, Liu M, Moore K, Currie S, Schlijper R, Bauman GS, Laba J, Qu XM, Warner A, Senan S. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol. 2020 Sep 1;38(25):2830-2838. doi: 10.1200/JCO.20.00818. Epub 2020 Jun 2.
• Background Jain V, Berman AT. Radiation Pneumonitis: Old Problem, New Tricks. Cancers (Basel). 2018 Jul 3;10(7):222. doi: 10.3390/cancers10070222.
• Background Maria OM, Maria AM, Ybarra N, Jeyaseelan K, Lee S, Perez J, Shalaby MY, Lehnert S, Faria S, Serban M, Seuntjens J, El Naqa I. Mesenchymal Stem Cells Adopt Lung Cell Phenotype in Normal and Radiation-induced Lung Injury Conditions. Appl Immunohistochem Mol Morphol. 2016 Apr;24(4):283-95. doi: 10.1097/PAI.0000000000000180.
• Background Perez JR, Ybarra N, Chagnon F, Serban M, Lee S, Seuntjens J, Lesur O, El Naqa I. Tracking of Mesenchymal Stem Cells with Fluorescence Endomicroscopy Imaging in Radiotherapy-Induced Lung Injury. Sci Rep. 2017 Jan 19;7:40748. doi: 10.1038/srep40748.
• Background Lee KC, Lin HC, Huang YH, Hung SC. Allo-transplantation of mesenchymal stem cells attenuates hepatic injury through IL1Ra dependent macrophage switch in a mouse model of liver disease. J Hepatol. 2015 Dec;63(6):1405-12. doi: 10.1016/j.jhep.2015.07.035. Epub 2015 Aug 11.
• Background Islam D, Huang Y, Fanelli V, Delsedime L, Wu S, Khang J, Han B, Grassi A, Li M, Xu Y, Luo A, Wu J, Liu X, McKillop M, Medin J, Qiu H, Zhong N, Liu M, Laffey J, Li Y, Zhang H. Identification and Modulation of Microenvironment Is Crucial for Effective Mesenchymal Stromal Cell Therapy in Acute Lung Injury. Am J Respir Crit Care Med. 2019 May 15;199(10):1214-1224. doi: 10.1164/rccm.201802-0356OC.
• Background Duan X, Lu L, Wang Y, Zhang F, Mao J, Cao M, Lin B, Zhang X, Shuai X, Shen J. The long-term fate of mesenchymal stem cells labeled with magnetic resonance imaging-visible polymersomes in cerebral ischemia. Int J Nanomedicine. 2017 Sep 8;12:6705-6719. doi: 10.2147/IJN.S146742. eCollection 2017.
• Background Bruder SP, Jaiswal N, Ricalton NS, Mosca JD, Kraus KH, Kadiyala S. Mesenchymal stem cells in osteobiology and applied bone regeneration. Clin Orthop Relat Res. 1998 Oct;(355 Suppl):S247-56. doi: 10.1097/00003086-199810001-00025.
• Background Zhou Y, Yamamoto Y, Xiao Z, Ochiya T. The Immunomodulatory Functions of Mesenchymal Stromal/Stem Cells Mediated via Paracrine Activity. J Clin Med. 2019 Jul 12;8(7):1025. doi: 10.3390/jcm8071025.
• Background Song N, Scholtemeijer M, Shah K. Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential. Trends Pharmacol Sci. 2020 Sep;41(9):653-664. doi: 10.1016/j.tips.2020.06.009. Epub 2020 Jul 22.
• Background Li L, Chen X, Wang WE, Zeng C. How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart? Stem Cells Int. 2016;2016:9682757. doi: 10.1155/2016/9682757. Epub 2015 Nov 22.
• Background Sun T, Gao F, Li X, Cai Y, Bai M, Li F, Du L. A combination of ultrasound-targeted microbubble destruction with transplantation of bone marrow mesenchymal stem cells promotes recovery of acute liver injury. Stem Cell Res Ther. 2018 Dec 29;9(1):356. doi: 10.1186/s13287-018-1098-4.
• Background Ramalho BDS, Almeida FM, Sales CM, de Lima S, Martinez AMB. Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice. Neural Regen Res. 2018 Jun;13(6):1046-1053. doi: 10.4103/1673-5374.233448.
• Background He X, Hong W, Yang J, Lei H, Lu T, He C, Bi Z, Pan X, Liu Y, Dai L, Wang W, Huang C, Deng H, Wei X. Spontaneous apoptosis of cells in therapeutic stem cell preparation exert immunomodulatory effects through release of phosphatidylserine. Signal Transduct Target Ther. 2021 Jul 14;6(1):270. doi: 10.1038/s41392-021-00688-z.
• Background Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest. 1998 Feb 15;101(4):890-8. doi: 10.1172/JCI1112.
• Background Ipseiz N, Uderhardt S, Scholtysek C, Steffen M, Schabbauer G, Bozec A, Schett G, Kronke G. The nuclear receptor Nr4a1 mediates anti-inflammatory effects of apoptotic cells. J Immunol. 2014 May 15;192(10):4852-8. doi: 10.4049/jimmunol.1303377. Epub 2014 Apr 16.
• Background Chang CL, Leu S, Sung HC, Zhen YY, Cho CL, Chen A, Tsai TH, Chung SY, Chai HT, Sun CK, Yen CH, Yip HK. Impact of apoptotic adipose-derived mesenchymal stem cells on attenuating organ damage and reducing mortality in rat sepsis syndrome induced by cecal puncture and ligation. J Transl Med. 2012 Dec 7;10:244. doi: 10.1186/1479-5876-10-244.
• Background Sung PH, Chang CL, Tsai TH, Chang LT, Leu S, Chen YL, Yang CC, Chua S, Yeh KH, Chai HT, Chang HW, Chen HH, Yip HK. Apoptotic adipose-derived mesenchymal stem cell therapy protects against lung and kidney injury in sepsis syndrome caused by cecal ligation puncture in rats. Stem Cell Res Ther. 2013;4(6):155. doi: 10.1186/scrt385.
• Background Chen HH, Lin KC, Wallace CG, Chen YT, Yang CC, Leu S, Chen YC, Sun CK, Tsai TH, Chen YL, Chung SY, Chang CL, Yip HK. Additional benefit of combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cell against sepsis-induced kidney injury. J Pineal Res. 2014 Aug;57(1):16-32. doi: 10.1111/jpi.12140. Epub 2014 May 15.
• Background Yip HK, Chang YC, Wallace CG, Chang LT, Tsai TH, Chen YL, Chang HW, Leu S, Zhen YY, Tsai CY, Yeh KH, Sun CK, Yen CH. Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemia-reperfusion injury. J Pineal Res. 2013 Mar;54(2):207-21. doi: 10.1111/jpi.12020. Epub 2012 Oct 30.

Drugs

Indications