PMID- 35511336 OWN - NLM STAT- MEDLINE DCOM- 20220919 LR - 20220929 IS - 2212-5469 (Electronic) IS - 1738-2696 (Print) IS - 1738-2696 (Linking) VI - 19 IP - 5 DP - 2022 Oct TI - A Comprehensive Cancer-Associated MicroRNA Expression Profiling and Proteomic Analysis of Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes. PG - 1013-1031 LID - 10.1007/s13770-022-00450-8 [doi] AB - BACKGROUND: The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. METHODS: Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and culture expanded. Subsequently, exosomes were isolated from hUCMSC conditioned medium and characterized by DLS, electron microscopy. Western blot for exosome surface marker protein CD63 expression was performed. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. RESULTS: The tri-lineage differentiation potential, fibroblastic morphology, and strong expression of pluripotency genes indicated that isolated fibroblasts are MSCs. The isolated extracellular vesicles were 133.8 +/- 42.49 nm in diameter, monodispersed, and strongly expressed the exosome surface marker protein CD63. The miRNA expression profile and gene ontology (GO) depicted the differential expression patterns of high and less-expressed miRNAs that are crucial to be involved in the regulation of apoptosis. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. CONCLUSION: Primary human MSCs released miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs have a critical influence in regulating cell death and apoptosis of cancer cells. CI - (c) 2022. The Author(s). FAU - Jothimani, Ganesan AU - Jothimani G AD - Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, Tamil Nadu, 603 103, India. FAU - Pathak, Surajit AU - Pathak S AD - Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, Tamil Nadu, 603 103, India. FAU - Dutta, Suman AU - Dutta S AD - International Institute of Innovation and Technology, DH Block, Action Area 1D, Newtown, Kolkata, West Bengal, 700156, India. FAU - Duttaroy, Asim K AU - Duttaroy AK AUID- ORCID: 0000-0003-1619-3778 AD - Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway. a.k.duttaroy@medisin.uio.no. FAU - Banerjee, Antara AU - Banerjee A AUID- ORCID: 0000-0002-5519-6878 AD - Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, Tamil Nadu, 603 103, India. antarabanerjee@care.edu.in. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220505 PL - Korea (South) TA - Tissue Eng Regen Med JT - Tissue engineering and regenerative medicine JID - 101699923 RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 0 (MicroRNAs) SB - IM MH - Culture Media, Conditioned/pharmacology MH - Cytokines/metabolism MH - *Exosomes/metabolism MH - Humans MH - *Mesenchymal Stem Cells/metabolism MH - *MicroRNAs/genetics/metabolism MH - *Neoplasms/metabolism MH - Proteomics MH - Umbilical Cord PMC - PMC9478013 OTO - NOTNLM OT - Cancer OT - Exosomes OT - Gene ontology OT - Mesenchymal stem cells OT - Proteome OT - Stem cell therapeutics OT - miRNA COIS- The authors declare that they have no conflict of interest. EDAT- 2022/05/06 06:00 MHDA- 2022/09/20 06:00 PMCR- 2022/05/05 CRDT- 2022/05/05 11:59 PHST- 2021/12/27 00:00 [received] PHST- 2022/03/04 00:00 [accepted] PHST- 2022/02/23 00:00 [revised] PHST- 2022/05/06 06:00 [pubmed] PHST- 2022/09/20 06:00 [medline] PHST- 2022/05/05 11:59 [entrez] PHST- 2022/05/05 00:00 [pmc-release] AID - 10.1007/s13770-022-00450-8 [pii] AID - 450 [pii] AID - 10.1007/s13770-022-00450-8 [doi] PST - ppublish SO - Tissue Eng Regen Med. 2022 Oct;19(5):1013-1031. doi: 10.1007/s13770-022-00450-8. Epub 2022 May 5.