Hanyang Med Rev.  2015 Nov;35(4):190-195. 10.7599/hmr.2015.35.4.190.

Induced Pluripotent Stem Cells: Next Generation Stem Cells to Clinical Applications

Affiliations
  • 1Department of Surgery, Hanyang University College of Medicine, Seoul, Korea.
  • 2Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Science, Seoul, Korea. sblee@kirams.re.kr

Abstract

Induced pluripotent stem cells (iPSC) are specially manipulated cells from somatic cells by the introduction of four factors that are reprogrammed. The properties of iPSC are similar to embryonic stem cells (ESC) characteristic of self-renewal and pluripotency. The technology of reprogramming somatic cells to iPSC enables the generation of patient-specific cells that can be used as powerful tools for drug screening, in vitro models for human disease and autologous transplantation. The iPSC technology provides a priceless resource for regenerative medicine but there are still changing obstacles over the safety of iPSC in avoiding induction of tumorigenicity and maintaining high purity of re-differentiated cells from iPSC to produce more functional cells for cell therapy. A variety of methods to overcome the limitation of iPSC application applied in the clinical setting have been developed. In this review, we summarize the recent progress in iPSC generation and differentiation techniques to facilitate clinical application of iPSC with future potential in regenerative medicine.

Keyword

Induced Pluripotent Stem Cells (iPSC); Cellular Reprogramming; Regenerative Medicine

MeSH Terms

Autografts
Cell- and Tissue-Based Therapy
Drug Evaluation, Preclinical
Embryonic Stem Cells
Humans
Induced Pluripotent Stem Cells*
Regenerative Medicine
Stem Cells*
Transplantation, Autologous

Figure

  • Fig. 1 Mophology and expression of hESC-specific surface antigen on human fibroblast transduced with cre-excisable reprogramming factors during the course of reprogramming. Transduced fibroblasts with cre-excisable polycistronic lentivirus containing reprogramming four factors (klf4, oct4, sox2, and c-myc) were cultured for indicated days on mouse embryonic fibroblast (MEF) in hESC medium. Picture shows the morphology (left) and livestaining of Tra 1-81 (right), surface marker of pluripotent stem cells on transduced fibroblasts during culture. Medium was changed daily. MEF used as feeder cells. Bars indicate 100 µm. hESC, human embryonic stem cells.

  • Fig. 2 Expression of hESC surface antigens and pluripotent markers in integration free-hiPSC derived from human fibroblast. iPSC coloies were picked up and sub-cultured. (A) Images of sub-cultured iPS and livestaining of surface antigen (SSEA4 and Tra1-60). Bars indicate 100 µm. (B) Immunostaining of pluripotent markers of hiPSC at passage 6. Bars indicate 100 µm. hESC, human embryonic stem cells; hiPSC, human induced pluripotent stem cells; iPSC, induced pluripotent stem cells; SSEA4, stage specific embryonic antigen 4.


Cited by  1 articles

New Horizons in Stem Cell Research
Dongho Choi
Hanyang Med Rev. 2015;35(4):187-189.    doi: 10.7599/hmr.2015.35.4.187.


Reference

1. Keating A. Mesenchymal stromal cells: new directions. Cell Stem Cell. 2012; 10:709–716.
Article
2. Svendsen CN. Back to the future: how human induced pluripotent stem cells will transform regenerative medicine. Hum Mol Genet. 2013; 22:R32–R38.
Article
3. Chen KG, Mallon BS, McKay RD, Robey PG. Human pluripotent stem cell culture: considerations for maintenance, expansion, and therapeutics. Cell Stem Cell. 2014; 14:13–26.
Article
4. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126:663–676.
Article
5. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007; 131:861–872.
Article
6. Wakayama S, Jakt ML, Suzuki M, Araki R, Hikichi T, Kishigami S, et al. Equivalency of nuclear transfer-derived embryonic stem cells to those derived from fertilized mouse blastocysts. Stem Cells. 2006; 24:2023–2033.
Article
7. Brambrink T, Hochedlinger K, Bell G, Jaenisch R. ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable. Proc Natl Acad Sci U S A. 2006; 103:933–938.
Article
8. Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, et al. Transgenic bovine chimeric offspring produced from somatic cell-derived stem-like cells. Nat Biotechnol. 1998; 16:642–646.
Article
9. Wakayama T, Tabar V, Rodriguez I, Perry AC, Studer L, Mombaerts P. Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science. 2001; 292:740–743.
Article
10. Rajamohan D, Matsa E, Kalra S, Crutchley J, Patel A, George V, et al. Current status of drug screening and disease modelling in human pluripotent stem cells. Bioessays. 2013; 35:281–298.
Article
11. Halevy T, Urbach A. Comparing ESC and iPSC-Based Models for Human Genetic Disorders. J Clin Med. 2014; 3:1146–1162.
Article
12. Ben-David U, Gan QF, Golan-Lev T, Arora P, Yanuka O, Oren YS, et al. Selective elimination of human pluripotent stem cells by an oleate synthesis inhibitor discovered in a high-throughput screen. Cell Stem Cell. 2013; 12:167–179.
Article
13. Lee MO, Moon SH, Jeong HC, Yi JY, Lee TH, Shim SH, et al. Inhibition of pluripotent stem cell-derived teratoma formation by small molecules. Proc Natl Acad Sci U S A. 2013; 110:E3281–E3290.
Article
14. Sasai Y. Next-generation regenerative medicine: organogenesis from stem cells in 3D culture. Cell Stem Cell. 2013; 12:520–530.
Article
15. Ranga A, Gjorevski N, Lutolf MP. Drug discovery through stem cell-based organoid models. Adv Drug Deliv Rev. 2014; 69-70:19–28.
Article
16. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007; 318:1917–1920.
Article
17. Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2008; 26:101–106.
Article
18. Malik N, Rao MS. A review of the methods for human iPSC derivation. Methods Mol Biol. 2013; 997:23–33.
Article
19. Higuchi A, Ling QD, Kumar SS, Munusamy MA, Alarfaj AA, Chang Y, et al. Generation of pluripotent stem cells without the use of genetic material. Lab Invest. 2015; 95:26–42.
Article
20. Stadtfeld M, Hochedlinger K. Induced pluripotency: history, mechanisms, and applications. Genes Dev. 2010; 24:2239–2263.
Article
21. Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, et al. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell. 2009; 136:964–977.
Article
22. Sommer CA, Sommer AG, Longmire TA, Christodoulou C, Thomas DD, Gostissa M, et al. Excision of reprogramming transgenes improves the differentiation potential of iPS cells generated with a single excisable vector. Stem Cells. 2010; 28:64–74.
Article
23. Zhou W, Freed CR. Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells. 2009; 27:2667–2674.
Article
24. Nishimura K, Sano M, Ohtaka M, Furuta B, Umemura Y, Nakajima Y, et al. Development ofdefective and persistent Sendai virus vector: a unique gene delivery/expression system ideal for cell reprogramming. J Biol Chem. 2011; 286:4760–4771.
25. Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, et al. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell. 2009; 4:381–384.
Article
26. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, et al. Highly efficient reprogrammingto pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell. 2010; 7:618–630.
Article
27. Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, et al. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell. 2011; 8:376–388.
Article
28. Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, et al. Human induced pluripotentstem cells free of vector and transgene sequences. Science. 2009; 324:797–801.
Article
29. Orkin SH, Hochedlinger K. Chromatin connections to pluripotency and cellular reprogramming. Cell. 2011; 145:835–850.
Article
30. Liang G, Zhang Y. Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective. Cell Res. 2013; 23:49–69.
Article
31. Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol. 2008; 26:795–797.
Article
32. Huangfu D, Osafune K, Maehr R, Guo W, Eijkelenboom A, Chen S, et al. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol. 2008; 26:1269–1275.
Article
33. Mali P, Chou BK, Yen J, Ye Z, Zou J, Dowey S, et al. Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes. Stem Cells. 2010; 28:713–720.
Article
34. Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science. 2013; 341:651–654.
Article
35. Lowry WE, Richter L, Yachechko R, Pyle AD, Tchieu J, Sridharan R, et al. Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci U S A. 2008; 105:2883–2888.
Article
36. Lee SB, Seo D, Choi D, Park KY, Holczbauer A, Marquardt JU, et al. Contribution of hepatic lineage stage-specific donor memory to the differential potential of induced mouse pluripotent stem cells. Stem Cells. 2012; 30:997–1007.
Article
37. Acimovic I, Vilotic A, Pesl M, Lacampagne A, Dvorak P, Rotrekl V, et al. Human pluripotent stem cell-derived cardiomyocytes as research and therapeutic tools. BioMed Res Int. 2014; 2014:512831.
Article
38. Kim EM, Manzar G, Zavazava N. Human iPS cell-derived hematopoietic progenitor cells induce T-cell anergy in in vitro-generated alloreactive CD8(+) T cells. Blood. 2013; 121:5167–5175.
Article
39. Schondorf DC, Aureli M, McAllister FE, Hindley CJ, Mayer F, Schmid B, et al. iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic defects and impaired calcium homeostasis. Nat Commun. 2014; 5:4028.
Article
40. Sun C, Wilson GS, Fan JG, Qiao L. Potential applications of induced pluripotent stem cells (iPSCs) in hepatology research. Curr Stem Cell Res Ther. 2015; 10:208–215.
Article
41. Ye Z, Chou BK, Cheng L. Promise and challenges of human iPSC-based hematologic disease modeling and treatment. Int J Hematol. 2012; 95:601–609.
Article
42. Moledina F, Clarke G, Oskooei A, Onishi K, Gunther A, Zandstra PW. Predictive microfluidic control of regulatory ligand trajectories in individual pluripotent cells. Proc Natl Acad Sci U S A. 2012; 109:3264–3269.
Article
43. Lock LT, Tzanakakis ES. Expansion and differentiation of human embryonic stem cells to endoderm progeny in a microcarrier stirred-suspension culture. Tissue Eng Part A. 2009; 15:2051–2063.
Article
44. DeQuach JA, Mezzano V, Miglani A, Lange S, Keller GM, Sheikh F, et al. Simple and high yielding method for preparing tissue specific extracellular matrix coatings for cell culture. PLoS One. 2010; 5:e13039.
Article
45. Eiraku M, Takata N, Ishibashi H, Kawada M, Sakakura E, Okuda S, et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature. 2011; 472:51–56.
Article
46. Efthymiou A, Shaltouki A, Steiner JP, Jha B, Heman-Ackah SM, Swistowski A, et al. Functional screening assays with neurons generated from pluripotent stem cell-derived neural stem cells. J Biomol Screen. 2014; 19:32–43.
Article
47. Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature. 2011; 470:105–109.
Article
48. Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 2013; 499:481–484.
Article
49. Willenbring H, Soto-Gutierrez A. Transplantable liver organoids made from only three ingredients. Cell Stem Cell. 2013; 13:139–140.
Article
Full Text Links
  • HMR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr