The Novel Tool of Cell Reprogramming for Applications in Molecular Medicine

Overview

Journal J Mol Med (Berl)

Specialty General Medicine

Date 2017 Jun 10

PMID 28597071

Citations 10

Authors

Moritz Mall

Marius Wernig

Affiliations

Soon will be listed here.

Abstract

Recent discoveries in the field of stem cell biology have enabled scientists to "reprogram" cells from one type to another. For example, it is now possible to place adult skin or blood cells in a dish and convert them into neurons, liver, or heart cells. It is also possible to literally "rejuvenate" adult cells by reprogramming them into embryonic-like stem cells, which in turn can be differentiated into every tissue and cell type of the human body. Our ability to reprogram cell types has four main implications for medicine: (1) scientists can now take skin or blood cells from patients and convert them to other cells to study disease processes. This disease modeling approach has the advantage over animal models because it is directly based on human patient cells. (2) Reprogramming could also be used as a "clinical trial in a dish" to evaluate the general efficacy and safety of newly developed drugs on human patient cells before they would be tested in animal models or people. (3) In addition, many drugs have deleterious side effects like heart arrhythmias in only a small and unpredictable subpopulation of patients. Reprogramming could facilitate precision medicine by testing the safety of already approved drugs first on reprogrammed patient cells in a personalized manner prior to administration. For example, drugs known to sometimes cause arrhythmias could be first tested on reprogrammed heart cells from individual patients. (4) Finally, reprogramming allows the generation of new tissues that could be grafted therapeutically to regenerate lost or damaged cells.

Citing Articles

Next-generation direct reprogramming.

Keshri R, Detraux D, Phal A, McCurdy C, Jhajharia S, Chan T Front Cell Dev Biol. 2024; 12:1343106.

PMID: 38371924 PMC: 10869521. DOI: 10.3389/fcell.2024.1343106.

Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine.

Dhanjal D, Singh R, Sharma V, Nepovimova E, Adam V, Kuca K Curr Med Chem. 2023; 31(13):1646-1690.

PMID: 37138422 DOI: 10.2174/0929867330666230503144619.

Combining Cell Fate Reprogramming and Protein Engineering to Study Transcription Factor Functions.

Adrian-Segarra J, Weigel B, Mall M Methods Mol Biol. 2021; 2352:227-236.

PMID: 34324190 DOI: 10.1007/978-1-0716-1601-7_15.

Human sensory neurons derived from pluripotent stem cells for disease modelling and personalized medicine.

Lampert A, Bennett D, McDermott L, Neureiter A, Eberhardt E, Winner B Neurobiol Pain. 2020; 8:100055.

PMID: 33364527 PMC: 7750732. DOI: 10.1016/j.ynpai.2020.100055.

Next-generation disease modeling with direct conversion: a new path to old neurons.

Traxler L, Edenhofer F, Mertens J FEBS Lett. 2019; 593(23):3316-3337.

PMID: 31715002 PMC: 6907729. DOI: 10.1002/1873-3468.13678.

References

Halder G, Callaerts P, Gehring W . Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science. 1995; 267(5205):1788-92. DOI: 10.1126/science.7892602. View

Esch E, Bahinski A, Huh D . Organs-on-chips at the frontiers of drug discovery. Nat Rev Drug Discov. 2015; 14(4):248-60. PMC: 4826389. DOI: 10.1038/nrd4539. View

Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton D . In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature. 2008; 455(7213):627-32. PMC: 9011918. DOI: 10.1038/nature07314. View

Cahan P, Li H, Morris S, Lummertz da Rocha E, Daley G, Collins J . CellNet: network biology applied to stem cell engineering. Cell. 2014; 158(4):903-915. PMC: 4233680. DOI: 10.1016/j.cell.2014.07.020. View

Blau H, Pavlath G, Hardeman E, Chiu C, Silberstein L, Webster S . Plasticity of the differentiated state. Science. 1985; 230(4727):758-66. DOI: 10.1126/science.2414846. View

Ueki Y, Wilken M, Cox K, Chipman L, Jorstad N, Sternhagen K . Transgenic expression of the proneural transcription factor Ascl1 in Müller glia stimulates retinal regeneration in young mice. Proc Natl Acad Sci U S A. 2015; 112(44):13717-22. PMC: 4640735. DOI: 10.1073/pnas.1510595112. View

Guo Z, Zhang L, Wu Z, Chen Y, Wang F, Chen G . In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer's disease model. Cell Stem Cell. 2013; 14(2):188-202. PMC: 3967760. DOI: 10.1016/j.stem.2013.12.001. View

Morris S, Cahan P, Li H, Zhao A, San Roman A, Shivdasani R . Dissecting engineered cell types and enhancing cell fate conversion via CellNet. Cell. 2014; 158(4):889-902. PMC: 4291075. DOI: 10.1016/j.cell.2014.07.021. View

Wapinski O, Vierbuchen T, Qu K, Lee Q, Chanda S, Fuentes D . Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons. Cell. 2013; 155(3):621-35. PMC: 3871197. DOI: 10.1016/j.cell.2013.09.028. View

10.

Di Tullio A, Manh T, Schubert A, Castellano G, Mansson R, Graf T . CCAAT/enhancer binding protein alpha (C/EBP(alpha))-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation. Proc Natl Acad Sci U S A. 2011; 108(41):17016-21. PMC: 3193237. DOI: 10.1073/pnas.1112169108. View

11.

Wilmut I, Schnieke A, McWhir J, Kind A, Campbell K . Viable offspring derived from fetal and adult mammalian cells. Nature. 1997; 385(6619):810-3. DOI: 10.1038/385810a0. View

12.

Heins N, Malatesta P, Cecconi F, Nakafuku M, Tucker K, Hack M . Glial cells generate neurons: the role of the transcription factor Pax6. Nat Neurosci. 2002; 5(4):308-15. DOI: 10.1038/nn828. View

13.

Chronis C, Fiziev P, Papp B, Butz S, Bonora G, Sabri S . Cooperative Binding of Transcription Factors Orchestrates Reprogramming. Cell. 2017; 168(3):442-459.e20. PMC: 5302508. DOI: 10.1016/j.cell.2016.12.016. View

14.

Gurdon J, Byrne J . The first half-century of nuclear transplantation. Proc Natl Acad Sci U S A. 2003; 100(14):8048-52. PMC: 166179. DOI: 10.1073/pnas.1337135100. View

15.

Ahlenius H, Chanda S, Webb A, Yousif I, Karmazin J, Prusiner S . FoxO3 regulates neuronal reprogramming of cells from postnatal and aging mice. Proc Natl Acad Sci U S A. 2016; 113(30):8514-9. PMC: 4968717. DOI: 10.1073/pnas.1607079113. View

16.

Takeuchi J, Bruneau B . Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature. 2009; 459(7247):708-11. PMC: 2728356. DOI: 10.1038/nature08039. View

17.

Cheloufi S, Elling U, Hopfgartner B, Jung Y, Murn J, Ninova M . The histone chaperone CAF-1 safeguards somatic cell identity. Nature. 2015; 528(7581):218-24. PMC: 4866648. DOI: 10.1038/nature15749. View

18.

Han D, Tapia N, Hermann A, Hemmer K, Hoing S, Arauzo-Bravo M . Direct reprogramming of fibroblasts into neural stem cells by defined factors. Cell Stem Cell. 2012; 10(4):465-72. DOI: 10.1016/j.stem.2012.02.021. View

19.

Torper O, Pfisterer U, Wolf D, Pereira M, Lau S, Jakobsson J . Generation of induced neurons via direct conversion in vivo. Proc Natl Acad Sci U S A. 2013; 110(17):7038-43. PMC: 3637783. DOI: 10.1073/pnas.1303829110. View

20.

Yamada M, Johannesson B, Sagi I, Burnett L, Kort D, Prosser R . Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells. Nature. 2014; 510(7506):533-6. DOI: 10.1038/nature13287. View