Review Article

Looking Into the Future of Cell-Based Therapy

Authors: M William Lensch, PhD, Jason A. West, BS

Abstract

Recent research points to the future of regenerative medicine. In the past year, a handful of research groups have demonstrated that mature, adult cells could be “reprogrammed” to a very primitive, embryonic state via the forced expression of four genes (Oct-3/4, c-Myc, Klf4, and Sox2). These induced pluripotent cells (or iPS) share features with embryonic stem (ES) cells and generate tissues from all three embryonic germ layers (ectoderm, mesoderm, and endoderm). iPS cells are also capable of the ultimate demonstration of developmental potency, ie, when injected into an early mouse embryo, they contribute to the formation of an entire mouse including its germline. While the reprogramming of human fibroblasts into iPS cells remains to be seen, it is nevertheless difficult to overstate the value that this new research contributes to the field of regenerative medicine and its academic relative developmental biology. Herein, we attempt to bring these monumental works into greater focus and comment on how they work to shape the future of cellular therapies.


Key Points


* Recent breakthroughs point the way to the future of patient-specific, stem cell-based therapies.


* This recent work is but the latest milestone in a field spanning well over 100 years.


* The interplay between the fields of developmental biology and regenerative medicine is summarized.

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References

1. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663–676.
 
2. Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature 2007;448:313–317.
 
3. Wernig M, Meissner A, Foreman R, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 2007;448:318–324.
 
4. Maherali N, Sridharan R, Xie W, et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 2007;1:55–70.
 
5. Lensch MW, Daley GQ. Scientific and clinical opportunities for modeling blood disorders with embryonic stem cells. Blood 2006;107:2605–2612.
 
6. Spemann H. Embryonic Development and Induction. New Haven, CT, Yale University Press, 1938.
 
7. Briggs R, King TJ. Transplantation of living nuclei from blastula cells into enucleated frogs' eggs. Proc Natl Acad Sci U S A 1952;38:455–463.
 
8. Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 1962;10:622–640.
 
9. Wilmut I, Schnieke AE, McWhir J, et al. Viable offspring derived from fetal and adult mammalian cells. Nature 1997;385:810–813.
 
10. Eggan K, Baldwin K, Tackett M, et al. Mice cloned from olfactory sensory neurons. Nature 2004;428:44–49.
 
11. Hochedlinger K, Jaenisch R. Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature 2002;415:1035–1038.
 
12. Gurdon JB, Byrne JA. The first half-century of nuclear transplantation. Proc Natl Acad Sci U S A 2003;100:8048–8052.
 
13. Reik W, Walter J. Genomic imprinting: parental influence on the genome. Nat Rev Genet 2001;2:21–32.
 
14. Hochedlinger K, Jaenisch R. Nuclear reprogramming and pluripotency. Nature 2006;441:1061–1067.
 
15. National Research Council. Scientific and Medical Aspects of Human Reproductive Cloning. National Academies Press, Washington, DC, 2002.
 
16. Tamashiro KL, Wakayama T, Akutsu H, et al. Cloned mice have an obese phenotype not transmitted to their offspring. Nat Med 2002;8:262–267.
 
17. Kyba M, Perlingeiro RC, Daley GQ. HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell 2002;109:29–37.
 
18. Rideout WM3rd, Hochedlinger K, Kyba M, Daley GQ, Jaenisch R. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell 2002;109:17–27.
 
19. Steinbrook R. Egg donation and human embryonic stem-cell research. N Engl J Med 2006;354:324–326.
 
20. Chambers I, Colby D, Robertson M, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 2003;113:643–655.
 
21. Mitsui K, Tokuzawa Y, Itoh H, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 2003;113:631–642.
 
22. Yamanaka S. Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell 2007;1:39–49.
 
23. Boyer LA, Lee TI, Cole MF, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 2005;122:947–956.
 
24. Boyer LA, Plath K, Zeitlinger J, et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 2006;441:349–353.
 
25. Lee TI, Jenner RG, Boyer LA, et al. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 2006;125:301–313.
 
26. Wang J, Rao S, Chu J, et al. A protein interaction network for pluripotency of embryonic stem cells. Nature 2006;444:364–368.
 
27. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861–872.
 
28. Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells. Science 2007 (advance online publication).