Human Peripheral Blood Mononucleocyte Derived Myeloid Committed Progenitor Cells Mitigate H-ARS by Exosomal Paracrine Signal
Abstract
:1. Introduction
2. Results
2.1. Transplantation of hMCP Cells Mitigates h-ARS and Improves Survival
2.2. hMCP Rescues HSCs and Induces Regenerative Potential against Radiation Injury
2.3. hMCPs Are Suitable for Allogenic Transplant
2.4. hMCP-Derived Paracrine Signals Are Enriched with Exosomal Proteins
2.5. hMCP-Derived sEVs Mitigates h-ARS
2.6. hMCP sEVs Promote Regenerative Response of HSCs
2.7. hMCP-Derived sEVs miRNAs-Associated Regenerative and Immune-Modulatory Process
3. Discussion
4. Materials and Methods
4.1. Human Myeloid-Committed Progenitor Cell (hMCP) Culture
4.2. Characterization of hMCP
4.3. Collection of hMCP-Conditioned Media
4.4. Isolation of Small Extracellular Vesicles (sEVs) from hMCP-Conditioned Media
4.5. Characterization of sEVs
4.6. sEVs Protein Estimation and Particle Count
4.7. Nanoparticle Tracking Analysis (NTA) of sEVs
4.8. Exosomal miRNA Analysis
4.9. T Cells Inhibition Assay
4.10. Mice
4.11. Irradiation
4.12. Assessment of Graft Vs Host Disease (GVHD)
4.13. Bone Marrow Cell Analysis
4.14. Histology of Bone Marrow
4.15. Ex Vivo Colony-Forming Unit (CFU) Assay
4.16. Proteomics Analysis of hMCP-Conditioned Media
4.17. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Identified miRNA | p-Value | Counts | Target Genes |
---|---|---|---|
Hematopoietic Stem Cell Proliferation | |||
hsa-miR-22-3p | 0.007 | 52 | CTC1, MECOM, WNT1 |
hsa-miR-148a-3p | 0.017 | 11 | WNT1, WNT10B, WNT2B |
hsa-miR-1246 | 0.029 | 2038 | CTC1, PIM1 |
hsa-miR-19b-3p | 0.012 | 69 | ARIH2, ATXN1L, CD34, EIF2AK2, MECOM, N4BP2L2, SFRP2, THPO, WNT1, WNT2B |
hsa-miR-495-3p | 0.033 | 11 | ACE, ARIH2, ATXN1L, CTC1, EIF2AK2, MECOM, N4BP2L2, NKAP, RUNX1, SFRP2, WNT2B |
hsa-miR-765 | 0.040 | 83 | ACE, ARIH2, ATXN1L, CD34, EIF2AK2, ETV6, NKAP, PIM1, RUNX1, WNT1, WNT10B, WNT2B |
hsa-miR-582-5p | 0.004 | 12 | ACE, ARIH2, ATXN1L, CTC1, EIF2AK2, MECOM, N4BP2L2, NKAP, PDCD2, PIM1, RUNX1, SFRP2, THPO, WNT1, WNT10B, WNT2B |
hsa-miR-1915-3p | 0.018 | 613 | ACE, ARIH2, ATXN1L, CD34, CTC1, EIF2AK2, ETV6, N4BP2L2, NKAP, PDCD2, PIM1, RUNX1, SFRP2, THPO, WNT1, WNT10B, WNT2B |
hsa-miR-570-3p | 0.031 | 11 | ARIH2, ATXN1L, CD34, CTC1, EIF2AK2, ETV6, MECOM, N4BP2L2, NKAP, PDCD2, PIM1, RUNX1, SFRP2, WNT1, WNT10B, WNT2B |
hsa-miR-148b-3p | 0.034 | 18 | ACE, ARIH2, ATXN1L, CTC1, EIF2AK2, ETV6, MECOM, N4BP2L2, PDCD2, RUNX1, THPO, WNT1, WNT10B, WNT2B |
hsa-miR-4516 | 0.046 | 2637 | ACE, ARIH2, ATXN1L, CD34, CTC1, EIF2AK2, ETV6, N4BP2L2, NKAP, PDCD2, PIM1, RUNX1, THPO, WNT1, WNT10B, WNT2B |
Hematopoietic Stem Cell Homeostasis | |||
hsa-miR-130a-3p | 0.044 | 13 | CCN3, NLE1, TCIRG1, UBAP2L |
Hematopoietic Cell Lineage | |||
hsa-miR-451a | 0.010 | 10 | IL6, IL6R |
hsa-miR-34a-5p | 0.013 | 16 | CD24, CD44, CSF1R, IL6R, ITGA6, ITGB3, KIT, TFRC, TNF |
hsa-miR-148b-3p | 0.022 | 18 | CSF1, ITGA5 |
hsa-miR-34a-5p | 0.031 | 16 | CD24, CD44, CSF1R, IL6R, KIT |
hsa-miR-451a | 0.035 | 10 | IL6, IL6R |
Hematopoietic Stem Cell Differentiation | |||
hsa-miR-223-3p | 0.007 | 46 | IL6, LMO2, STAT5A |
hsa-miR-146a-5p | 0.008 | 66 | CXCR4, FOS, IL6, NOTCH1 |
hsa-miR-184 | 0.020 | 24 | CSF1, NFATC2 |
hsa-miR-34a-5p | 0.028 | 16 | FOS, KCNH2, LEF1, MYB, NOTCH1 |
hsa-miR-223-3p | 0.041 | 46 | IL6, LMO2, STAT5A |
hsa-miR-155-5p | 0.044 | 268 | FLI1, FOS, IL6, MXI1, MYB, SPI1, THRB |
hsa-miR-34a-5p | 0.047 | 16 | FOS, ITGB3, KCNH2, LEF1, MYB, NOTCH1 |
Regulation of Hematopoietic Stem Cell Differentiation | |||
hsa-miR-615-3p | 0.048 | 13 | CBFB, CDK6, HSPA9, PSMB7, PSMD13, PSMD2, PSMD8, PSMF1, TCF3, YTHDF2 |
hsa-miR-105-5p | 0.018 | 17 | CDK6, MYB |
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Chugh, R.M.; Bhanja, P.; Olea, X.D.; Tao, F.; Schroeder, K.; Zitter, R.; Arora, T.; Pathak, H.; Kimler, B.F.; Godwin, A.K.; et al. Human Peripheral Blood Mononucleocyte Derived Myeloid Committed Progenitor Cells Mitigate H-ARS by Exosomal Paracrine Signal. Int. J. Mol. Sci. 2022, 23, 5498. https://doi.org/10.3390/ijms23105498
Chugh RM, Bhanja P, Olea XD, Tao F, Schroeder K, Zitter R, Arora T, Pathak H, Kimler BF, Godwin AK, et al. Human Peripheral Blood Mononucleocyte Derived Myeloid Committed Progenitor Cells Mitigate H-ARS by Exosomal Paracrine Signal. International Journal of Molecular Sciences. 2022; 23(10):5498. https://doi.org/10.3390/ijms23105498
Chicago/Turabian StyleChugh, Rishi Man, Payel Bhanja, Ximena Diaz Olea, Fang Tao, Kealan Schroeder, Ryan Zitter, Tanu Arora, Harsh Pathak, Bruce F. Kimler, Andrew K. Godwin, and et al. 2022. "Human Peripheral Blood Mononucleocyte Derived Myeloid Committed Progenitor Cells Mitigate H-ARS by Exosomal Paracrine Signal" International Journal of Molecular Sciences 23, no. 10: 5498. https://doi.org/10.3390/ijms23105498