Login Register Cart 0
General Review Article

Partial Reprogramming As An Emerging Strategy for Safe Induced Cell Generation and Rejuvenation

Author(s): Marianne Lehmann, Martina Canatelli-Mallat, Priscila Chiavellini, Gloria M. Cónsole, Maria D. Gallardo and Rodolfo G. Goya*

Volume 19, Issue 4, 2019

Page: [248 - 254] Pages: 7

DOI: 10.2174/1566523219666190902154511

Price: $65

Abstract

Background: Conventional cell reprogramming involves converting a somatic cell line into induced pluripotent stem cells (iPSC), which subsequently can be re-differentiated to specific somatic cell types. Alternatively, partial cell reprogramming converts somatic cells into other somatic cell types by transient expression of pluripotency genes thus generating intermediates that retain their original cell identity, but are responsive to appropriate cocktails of specific differentiation factors. Additionally, biological rejuvenation by partial cell reprogramming is an emerging avenue of research.

Objective: Here, we will briefly review the emerging information pointing to partial reprogramming as a suitable strategy to achieve cell reprogramming and rejuvenation, bypassing cell dedifferentiation.

Methods: In this context, regulatable pluripotency gene expression systems are the most widely used at present to implement partial cell reprogramming. For instance, we have constructed a regulatable bidirectional adenovector expressing Green Fluorescent Protein and oct4, sox2, klf4 and c-myc genes (known as the Yamanaka genes or OSKM).

Results: Partial cell reprogramming has been used to reprogram fibroblasts to cardiomyocytes, neural progenitors and neural stem cells. Rejuvenation by cyclic partial reprogramming has been achieved both in vivo and in cell culture using transgenic mice and cells expressing the OSKM genes, respectively, controlled by a regulatable promoter.

Conclusion: Partial reprogramming emerges as a powerful tool for the genesis of iPSC-free induced somatic cells of therapeutic value and for the implementation of in vitro and in vivo rejuvenation keeping cell type identity unchanged.

Keywords: Partial reprogramming, pluripotency, cell identity, rejuvenation, iPSC, somatic cells.

« Previous Next »
Graphical Abstract

[1]
Gurdon JB. From nuclear transfer to nuclear reprogramming: The reversal of cell differentiation. Annu Rev Cell Dev Biol 2006; 22: 1-22.
[http://dx.doi.org/10.1146/annurev.cellbio.22.090805.140144] [PMID: 16704337]
[2]
Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 1962; 10: 622-40.
[PMID: 13951335]
[3]
Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Nature 1997; 385(6619): 810-3.
[http://dx.doi.org/10.1038/385810a0] [PMID: 9039911]
[4]
Hochedlinger K, Jaenisch R. Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature 2002; 415(6875): 1035-8.
[http://dx.doi.org/10.1038/nature718] [PMID: 11875572]
[5]
Meng L, Ely JJ, Stouffer RL, Wolf DP. Rhesus monkeys produced by nuclear transfer. Biol Reprod 1997; 57(2): 454-9.
[http://dx.doi.org/10.1095/biolreprod57.2.454] [PMID: 9241063]
[6]
Grisham J. Pigs cloned for first time. Nat Biotechnol 2000; 18(4): 365-7.
[http://dx.doi.org/10.1038/74335] [PMID: 10748477]
[7]
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663-76.
[http://dx.doi.org/10.1016/j.cell.2006.07.024] [PMID: 16904174]
[8]
López-León M, Outeiro TF, Goya RG. Cell reprogramming: Therapeutic potential and the promise of rejuvenation for the aging brain. Ageing Res Rev 2017; 40: 168-81.
[http://dx.doi.org/10.1016/j.arr.2017.09.002] [PMID: 28903069]
[9]
López-León M, Goya RG. The emerging view of aging as a reversible epigenetic process. Gerontology 2017; 63(5): 426-31.
[http://dx.doi.org/10.1159/000477209] [PMID: 28538216]
[10]
Okano H, Nakamura M, Yoshida K, et al. Steps toward safe cell therapy using induced pluripotent stem cells. Circ Res 2013; 112(3): 523-33.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.256149] [PMID: 23371901]
[11]
Miura K, Okada Y, Aoi T, et al. Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol 2009; 27(8): 743-5.
[http://dx.doi.org/10.1038/nbt.1554] [PMID: 19590502]
[12]
Kim J, Ambasudhan R, Ding S. Direct lineage reprogramming to neural cells. Curr Opin Neurobiol 2012; 22(5): 778-84.
[http://dx.doi.org/10.1016/j.conb.2012.05.001] [PMID: 22652035]
[13]
Kim SM, Flaßkamp H, Hermann A, et al. Direct conversion of mouse fibroblasts into induced neural stem cells. Nat Protoc 2014; 9(4): 871-81.
[http://dx.doi.org/10.1038/nprot.2014.056] [PMID: 24651499]
[14]
Kim J, Efe JA, Zhu S, et al. Direct reprogramming of mouse fibroblasts to neural progenitors. Proc Natl Acad Sci USA 2011; 108(19): 7838-43.
[http://dx.doi.org/10.1073/pnas.1103113108] [PMID: 21521790]
[15]
Efe JA, Hilcove S, Kim J, et al. Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat Cell Biol 2011; 13(3): 215-22.
[http://dx.doi.org/10.1038/ncb2164] [PMID: 21278734]
[16]
Ma T, Xie M, Laurent T, Ding S. Progress in the reprogramming of somatic cells. Circ Res 2013; 112(3): 562-74.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.249235] [PMID: 23371904]
[17]
Stadtfeld M, Maherali N, Breault DT, Hochedlinger K. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2008; 2(3): 230-40.
[http://dx.doi.org/10.1016/j.stem.2008.02.001] [PMID: 18371448]
[18]
Brambrink T, Foreman R, Welstead GG, et al. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell 2008; 2(2): 151-9.
[http://dx.doi.org/10.1016/j.stem.2008.01.004] [PMID: 18371436]
[19]
Hanna J, Saha K, Pando B, et al. Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 2009; 462(7273): 595-601.
[http://dx.doi.org/10.1038/nature08592] [PMID: 19898493]
[20]
Artyomov MN, Meissner A, Chakraborty AK. A model for genetic and epigenetic regulatory networks identifies rare pathways for transcription factor induced pluripotency. PLOS Comput Biol 2010; 6(5)e1000785
[http://dx.doi.org/10.1371/journal.pcbi.1000785] [PMID: 20485562]
[21]
Guo L, Karoubi G, Duchesneau P, et al. Generation of induced progenitor-like cells from mature epithelial cells using interrupted reprogramming. Stem Cell Reports 2017; 9(6): 1780-95.
[http://dx.doi.org/10.1016/j.stemcr.2017.10.022] [PMID: 29198829]
[22]
Maza I, Caspi I, Zviran A, et al. Transient acquisition of pluripotency during somatic cell transdifferentiation with iPSC reprogramming factors. Nat Biotechnol 2015; 33(7): 769-74.
[http://dx.doi.org/10.1038/nbt.3270] [PMID: 26098448]
[23]
Bar-Nur O, Verheul C, Sommer AG, et al. Lineage conversion induced by pluripotency factors involves transient passage through an iPSC stage. Nat Biotechnol 2015; 33(7): 761-8.
[http://dx.doi.org/10.1038/nbt.3247] [PMID: 26098450]
[24]
Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 1987; 51(6): 987-1000.
[http://dx.doi.org/10.1016/0092-8674(87)90585-X] [PMID: 3690668]
[25]
Ieda M, Fu JD, Delgado-Olguin P, et al. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 2010; 142(3): 375-86.
[http://dx.doi.org/10.1016/j.cell.2010.07.002] [PMID: 20691899]
[26]
Sancho-Martinez I, Baek SH, Izpisua BJC. Lineage conversion methodologies meet the reprogramming toolbox. Nat Cell Biol 2012; 14(9): 892-9.
[http://dx.doi.org/10.1038/ncb2567] [PMID: 22945254]
[27]
Mertens J, Paquola ACM, Ku M, et al. Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell 2015; 17(6): 705-18.
[http://dx.doi.org/10.1016/j.stem.2015.09.001] [PMID: 26456686]
[28]
Abad M, Mosteiro L, Pantoja C, et al. Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature 2013; 502(7471): 340-5.
[http://dx.doi.org/10.1038/nature12586] [PMID: 24025773]
[29]
Ohnishi K, Semi K, Yamamoto T, et al. Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation. Cell 2014; 156(4): 663-77.
[http://dx.doi.org/10.1016/j.cell.2014.01.005] [PMID: 24529372]
[30]
Ocampo A, Reddy P, Martinez-Redondo P, et al. In vivo amelioration of age- associated hallmarks by partial reprogramming. Cell 2016; 167(7): 1719-33.e12.
[http://dx.doi.org/10.1016/j.cell.2016.11.052] [PMID: 27984723]
[31]
de Lázaro I, Cossu G, Kostarelos K. Transient transcription factor (OSKM) expression is key towards clinical translation of in vivo cell reprogramming. EMBO Mol Med 2017; 9(6): 733-6.
[http://dx.doi.org/10.15252/emmm.201707650] [PMID: 28455313]
[32]
Olova N, Simpson DJ, Marioni RE, Chandra T. Partial reprogramming induces a steady decline in epigenetic age before loss of somatic identity. Aging Cell 2019; 18(1)e12877
[http://dx.doi.org/10.1111/acel.12877] [PMID: 30450724]
[33]
Tamanini S, Comi GP, Corti S. In vivo transient and partial cell reprogramming to pluripotency as a therapeutic tool for neurodegenerative diseases. Mol Neurobiol 2018; 55(8): 6850-62.
[http://dx.doi.org/10.1007/s12035-018-0888-0] [PMID: 29353456]
[34]
Göbel C, Goetzke R, Eggermann T, Wagner W. Interrupted reprogramming into induced pluripotent stem cells does not rejuvenate human mesenchymal stromal cells. Sci Rep 2018; 8(1): 11676.
[http://dx.doi.org/10.1038/s41598-018-30069-6] [PMID: 30076334]
[35]
Lu Y, Krishnan A, Brommer B, et al. Reversal of ageing- and injury-induced vision loss by Tet-dependent; epigenetic reprogramming. Available from:https://www.biorxiv.org/content/10.1101/710210v1
[http://dx.doi.org/10.1101/710210]
[36]
Zhou W, Freed CR. Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells 2009; 27(11): 2667-74.
[http://dx.doi.org/10.1002/stem.201] [PMID: 19697349]
[37]
Oka K, Chan L. Helper-dependent adenoviral vectors. Curr Protoc Mol Biol 2005; Chapter 16: 16.24.
[38]
Lehmann M, Canatelli-Mallat M, Chiavellini P, et al. Regulatable adenovector harboring the GFP and Yamanaka genes for implementing regenerative medicine in the brain. Gene Ther (in press)
[http://dx.doi.org/10.1038/s41434-019-0063-x] [PMID: 30770896]
[39]
Lu KH, Hopper BR, Vargo TM, Yen SS. Chronological changes in sex steroid, gonadotropin and prolactin secretions in aging female rats displaying different reproductive states. Biol Reprod 1979; 21(1): 193-203.
[http://dx.doi.org/10.1095/biolreprod21.1.193] [PMID: 573635]
[40]
Goya RG, Lu JKH, Meites J. Gonadal function in aging rats and its relation to pituitary and mammary pathology. Mech Ageing Dev 1990; 56(1): 77-88.
[http://dx.doi.org/10.1016/0047-6374(90)90116-W] [PMID: 2259256]
[41]
Sánchez HL, Silva LB, Portiansky EL, Goya RG, Zuccolilli GO. Impact of very old age on hypothalamic dopaminergic neurons in the female rat: A morphometric study. J Comp Neurol 2003; 458(4): 319-25.
[http://dx.doi.org/10.1002/cne.10564] [PMID: 12619067]
[42]
Sarkar DK, Gottschall PE, Meites J. Damage to hypothalamic dopaminergic neurons is associated with development of prolactin-secreting pituitary tumors. Science 1982; 218(4573): 684-6.
[http://dx.doi.org/10.1126/science.7134966] [PMID: 7134966]
[43]
Hereñú CB, Cristina C, Rimoldi OJ, et al. Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction. Gene Ther 2007; 14(3): 237-45.
[http://dx.doi.org/10.1038/sj.gt.3302870] [PMID: 16988717]
[44]
Schwerdt JI, López-León M, Console GM, et al. Rejuvenating effect of long-term IGF-I gene therapy in the hypothalamus of aged rats with dopaminergic dysfunction. Rejuvenation Res 2018; 21: 102-8.
[http://dx.doi.org/10.1089/rej.2017.1935] [PMID: 28673122]
[45]
Morel GR, Sosa YE, Bellini MJ, et al. Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats. Neuroscience 2010; 167(3): 946-53.
[http://dx.doi.org/10.1016/j.neuroscience.2010.02.053] [PMID: 20219648]
[46]
Schwerdt JI, Goya GF, Calatayud MP, Hereñú CB, Reggiani PC, Goya RG. Magnetic field-assisted gene delivery: Achievements and therapeutic potential. Curr Gene Ther 2012; 12(2): 116-26.
[http://dx.doi.org/10.2174/156652312800099616] [PMID: 22348552]
[47]
Smolders S, Kessels S, Smolders SM, et al. Magnetofection is superior to other chemical transfection methods in a microglial cell line. J Neurosci Methods 2018; 293: 169-73.
[http://dx.doi.org/10.1016/j.jneumeth.2017.09.017] [PMID: 28970164]
[48]
Venero JL, Burguillos MA. Magnetofection as a new tool to study microglia biology. Neural Regen Res 2019; 14(5): 767-8.
[http://dx.doi.org/10.4103/1673-5374.249221] [PMID: 30688259]
[49]
Czugala M, Mykhaylyk O, Böhler P, et al. Efficient and safe gene delivery to human corneal endothelium using magnetic nanoparticles. Nanomedicine (Lond) 2016; 11(14): 1787-800.
[http://dx.doi.org/10.2217/nnm-2016-0144] [PMID: 27388974]
[50]
Pereyra AS, Mykhaylyk O, Lockhart EF, et al. Magnetofection enhances adenoviral vector-based gene delivery in skeletal muscle cells. J Nanomed Nanotechnol 2016; 7(2): 1-11.
[PMID: 27274908]

Rights & Permissions Print Cite
Article Metrics
51
8
© 2024 Bentham Science Publishers | Privacy Policy