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Can we reprogram senescent cells via antibody therapy?

Image credit: https://pixabay.com/it/illustrations/sistema-immunitario-difesa-infezione-1359197/

Antonio Carusillo
Antonio Carusillo Nov 11, 2020

[1]Blanchard, J., Xie, J., El-Mecharrafie, N. et al. Replacing reprogramming factors with antibodies selected from combinatorial antibody libraries. Nat Biotechnol 35, 960–968 (2017). https://doi.org/10.1038/nbt.3963

[2]Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors Takahashi, Kazutoshi et al. Cell, Volume 131, Issue 5, 861 - 872

[3]Wuputra, K., Ku, CC., Wu, DC. et al. Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells. J Exp Clin Cancer Res 39, 100 (2020). https://doi.org/10.1186/s13046-020-01584-0

[4]Riggs JW, Barrilleaux BL, Varlakhanova N, Bush KM, Chan V, Knoepfler PS. Induced pluripotency and oncogenic transformation are related processes. Stem Cells Dev. 2013 Jan 1;22(1):37-50. doi: 10.1089/scd.2012.0375. Epub 2012 Oct 26. PMID: 22998387; PMCID: PMC3528096.

[5]Functional antibody selection in ES cells Anna N. Melidoni, Michael R. Dyson, Sam Wormald, John McCafferty Proceedings of the National Academy of Sciences Oct 2013, 110 (44) 17802-17807; DOI: 10.1073/pnas.1312062110

Creative contributions

MicroRNA mediated cellular reprogramming - different contextual examples

Subash Chapagain
Subash Chapagain Nov 13, 2020

[1] Yoo, A. S., Staahl, B. T., Chen, L., and Crabtree, G. R. (2009). MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature 460, 642–646. doi: 10.1038/nature08139

[2]Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell. 2011 Apr 8;8(4):376-88. doi: 10.1016/j.stem.2011.03.001. Erratum in: Cell Stem Cell. 2012 Dec 7;11(6):853. PMID: 21474102; PMCID: PMC3090650.

[3]Yoo AS, Sun AX, Li L, et al. MicroRNA-mediated conversion of human fibroblasts to neurons. Nature. 2011;476(7359):228-231. Published 2011 Jul 13. doi:10.1038/nature10323

[4]Jayawardena TM, Egemnazarov B, Finch EA, Zhang L, Payne JA, Pandya K, Zhang Z, Rosenberg P, Mirotsou M, Dzau VJ. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res. 2012 May 25;110(11):1465-73. doi: 10.1161/CIRCRESAHA.112.269035.

BAM factors and direct neuronal reprogramming

Subash Chapagain
Subash Chapagain Nov 13, 2020

[1]Tsunemoto RK, Eade KT, Blanchard JW, Baldwin KK. Forward engineering neuronal diversity using direct reprogramming. The EMBO Journal. 2015 Jun;34(11):1445-1455. DOI: 10.15252/embj.201591402.

[2]Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010;463:1035–1041.

[3]Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Sudhof TC, Wernig M. Induction of human neuronal cells by defined transcription factors. Nature. 2011;476:220–223.

[4]Marro S, Pang ZP, Yang N, Tsai MC, Qu K, Chang HY, Sudhof TC, Wernig M. Direct lineage conversion of terminally differentiated hepatocytes to functional neurons. Cell Stem Cell. 2011;9:374–382

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General comments

Juran3 months ago
It sounds like a concrete experiment. Concerning the part of proving the activation/stimulus of senescent cells reprogramming, we could use cell cycle analysis using flow cytometry to see if cells entered the cell cycle. This, followed by transcriptomic data could be a more convincing proof of activation.