induced pluripotent stem cell (iPS)
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Introduction
Cells, similar to embryonic stem cells, derived from differentiated skin cells (keratinocytes), 1st in mice, then in humans
Clinical significance
- used to treat sickle cell anemia in mice
- induced from fibroblasts obtained from a patient with ALS[4]
- induced from fibroblasts obtained from a child with childhood spinal muscular atrophy/SMN deletions & transformed into motor neurons[5]
- fibroblasts from patients with Alzheimer's disease (AD), familial AD & sporadic AD induced to form iPS, then processed into neurons; differences in Abeta40 secretion, GSK3B, phospho-tau noted (see molecular pathology of AD)[9]
Procedure
- 4 transcription factors (Yamanaka factors) induce fibroblasts to form induced-pluripotent stem cells in mice:
- using RNA rather than DNA for transfection improves efficiency & minimizes risk of tumors
Complications
- technique that requires introduction of genes into adult cells can induce tumors if they insert into the wrong place
- transfection with mRNA rather than DNA may minimize risk of inducing tumors[5]
- iPS cells often contain genetic modifications (e.g., point mutations, copy number variations) & epigenetic modifications that could render iPS cells cancerous or cause them to self-destruct after continued division[6]
- screening protocols may be necessary[6]
- more immunogenic & more likely than embryonic stem cells to induce rejection[7]
Comparative biology
- induced pluripotent stem cell-derived dopaminergic progenitors functioned as midbrain dopaminergic neurons in Macaca fascicularis treated with the neurotoxin MPTP
- the mature dopaminergic neurons extended dense neurites into the striatum
- an increase in spontaneous movement of the monkeys after transplantation observed
- no neoplasms noted within 2 years
Notes
- fibroblasts may be converted directly into neurons without 1st creating induced pleuripotent stem cells[8]
- depleting Mbd3 allows nearly 100% of cells to be transformed into pluripotent stem cells[10]
- brief exposure of differentiated adult mouse cells to an acidic environment transforms them into the equivalent of induced pluripotent stem cells
- the cells are called STAP cells
- STAP cells reproduce themselves indefinitely & can be transformed into any differentiated cell type[11]
- inability of others to reproduce results[11]
- claims of misconduct[11]
- initial reports on STAP cells retracted[11]
More general terms
Additional terms
References
- ↑ Takahashi K et al, Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007, Nov 20, 131:861 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18035408 <Internet> http://dximages.cell.com/images/images/cell/ieps/3661.pdf Yu J et al, Induced pluripotent stem cells derived from human somatic cells. Science 2007, Nov 20 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18029452 <Internet> http://dx.doi.org/10.1126/science.1151526
- ↑ Hanna J et al, Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 2007, Dec 6 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18063756 <Internet> http://dx.doi.org/10.1126/science.1152092
- ↑ Wernig M et al, Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci USA 2008, 105:5856 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18391196
- ↑ 4.0 4.1 Dimos JT et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 2008 Jul 31; [e-pub ahead of print] <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18669821 <Internet> http://dx.doi.org/10.1126/science.1158799
Park I-H et al. Disease-specific induced pluripotent stem cells. Cell 2008 Aug 7; [e-pub ahead of print] <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18691744 <Internet> http://dx.doi.org/10.1016/j.cell.2008.07.041 - ↑ 5.0 5.1 5.2 Warren L et al. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 2010 Sep 30 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20888316 Journal Watch, Massachessetts Medical Society, Nov 3, 2010 http://www.jwatch.org
- ↑ 6.0 6.1 6.2 Hussein SM et al. Copy number variation and selection during reprogramming to pluripotency. Nature 2011 Mar 3; 471:58. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21368824
Gore A et al. Somatic coding mutations in human induced pluripotent stem cells. Nature 2011 Mar 3; 471:63. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21368825
Lister R et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 2011 Mar 3; 471:68. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21289626
Pera MF. Stem cells: The dark side of induced pluripotency. Nature 2011 Mar 3; 471:46 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21368819 - ↑ 7.0 7.1 Zhao T et al. Immunogenicity of induced pluripotent stem cells. Nature 2011 May 13; 474:212. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21572395
Mummery C. Induced pluripotent stem cells - A cautionary note. N Engl J Med 2011 Jun 2; 364:2160. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21631331 - ↑ 8.0 8.1 Pang ZP et al. Induction of human neuronal cells by defined transcription factors. Nature 2011 Aug 11; 476:220 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21617644
Caiazzo M et al. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 2011 Aug 11; 476:224. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21725324
Yoo AS et al. MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 2011 Aug 11; 476:228 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21753754
Sendtner M. Bespoke cells for the human brain. Nature 2011 Aug 11; 476:158 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21833079 - ↑ 9.0 9.1 Israel MA et al. Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature 2012 Jan 25; PMID: https://www.ncbi.nlm.nih.gov/pubmed/22278060
- ↑ 10.0 10.1 Rais Y et al. Deterministic direct reprogramming of somatic cells to pluripotency. Nature 2013 Oct 3; 502:65. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24048479 <Internet> http://www.nature.com/nature/journal/v502/n7469/full/nature12587.html
Loh KM and Lim B.Stem cells: Close encounters with full potential. Nature 2013 Oct 3; 502:41 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24048472 <Internet> http://www.nature.com/nature/journal/v502/n7469/full/nature12561.html - ↑ 11.0 11.1 11.2 11.3 11.4 Obokata H et al. Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature 2014 Jan 30; 505:641 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24476887
Obokata H et al. Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature 2014 Jan 30; 505:676 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24476891
Cyranoski D Mismatch alleged in acid-bath stem-cell experiment. Cell lines linked to blockbuster papers came from different mouse strain to that claimed, study suggests. Nature. March 27, 2014 http://www.nature.com/news/mismatch-alleged-in-acid-bath-stem-cell-experiment-1.14946
Nature editorial STAP retracted. Two retractions highlight long-standing issues of trust and sloppiness that must be addressed. Nature, July 2, 2014 http://www.nature.com/news/stap-retracted-1.15488 - ↑ Kikuchi T, Morizane A, Doi D et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model. Nature 2017 Aug 31; 548:592. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28858313 <Internet> http://www.nature.com/nature/journal/v548/n7669/full/nature23664.html