Induced pluripotent stem cell explained

Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka and Kazutoshi Takahashi in Kyoto, Japan, who together showed in 2006 that the introduction of four specific genes (named Myc, Oct3/4, Sox2 and Klf4), collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells.[1] Shinya Yamanaka was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent."[2]

Pluripotent stem cells hold promise in the field of regenerative medicine.[3] Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.

The most well-known type of pluripotent stem cell is the embryonic stem cell. However, since the generation of embryonic stem cells involves destruction (or at least manipulation)[4] of the pre-implantation stage embryo, there has been much controversy surrounding their use. Patient-matched embryonic stem cell lines can now be derived using somatic cell nuclear transfer (SCNT).

Since iPSCs can be derived directly from adult tissues, they not only bypass the need for embryos, but can be made in a patient-matched manner, which means that each individual could have their own pluripotent stem cell line. These unlimited supplies of autologous cells could be used to generate transplants without the risk of immune rejection. While the iPSC technology has not yet advanced to a stage where therapeutic transplants have been deemed safe, iPSCs are readily being used in personalized drug discovery efforts and understanding the patient-specific basis of disease.[5]

Yamanaka named iPSCs with a lower case "i" due to the popularity of the iPod and other products.[6] [7] [8] [9]

In his Nobel seminar, Yamanaka cited the earlier seminal work of Harold Weintraub on the role of myoblast determination protein 1 (MyoD) in reprogramming cell fate to a muscle lineage as an important precursor to the discovery of iPSCs.[10]

Production

See also: Reprogramming.

iPSCs are typically derived by introducing products of specific sets of pluripotency-associated genes, or "reprogramming factors", into a given cell type. The original set of reprogramming factors (also dubbed Yamanaka factors) are the transcription factors Oct4 (Pou5f1), Sox2, Klf4 and cMyc. While this combination is most conventional in producing iPSCs, each of the factors can be functionally replaced by related transcription factors, miRNAs, small molecules, or even non-related genes such as lineage specifiers.[11] It is also clear that pro-mitotic factors such as C-MYC/L-MYC or repression of cell cycle checkpoints, such as p53, are conduits to creating a compliant cellular state for iPSC reprogramming.[12]

iPSC derivation is typically a slow and inefficient process, taking one–two weeks for mouse cells and three–four weeks for human cells, with efficiencies around 0.01–0.1%. However, considerable advances have been made in improving the efficiency and the time it takes to obtain iPSCs. Upon introduction of reprogramming factors, cells begin to form colonies that resemble pluripotent stem cells, which can be isolated based on their morphology, conditions that select for their growth, or through expression of surface markers or reporter genes.

First generation (mouse)

Induced pluripotent stem cells were first generated by Shinya Yamanaka and Kazutoshi Takahashi at Kyoto University, Japan, in 2006.[1] They hypothesized that genes important to embryonic stem cell (ESC) function might be able to induce an embryonic state in adult cells. They chose twenty-four genes previously identified as important in ESCs and used retroviruses to deliver these genes to mouse fibroblasts. The fibroblasts were engineered so that any cells reactivating the ESC-specific gene, Fbx15, could be isolated using antibiotic selection.

Upon delivery of all twenty-four factors, ESC-like colonies emerged that reactivated the Fbx15 reporter and could propagate indefinitely. To identify the genes necessary for reprogramming, the researchers removed one factor at a time from the pool of twenty-four. By this process, they identified four factors, Oct4, Sox2, cMyc, and Klf4, which were each necessary and together sufficient to generate ESC-like colonies under selection for reactivation of Fbx15.

Second generation (mouse)

In June 2007, three separate research groups, including that of Yamanaka's, a Harvard/University of California, Los Angeles collaboration, and a group at MIT, published studies that substantially improved on the reprogramming approach, giving rise to iPSCs that were indistinguishable from ESCs. Unlike the first generation of iPSCs, these second generation iPSCs produced viable chimeric mice and contributed to the mouse germline, thereby achieving the 'gold standard' for pluripotent stem cells.

These second-generation iPSCs were derived from mouse fibroblasts by retroviral-mediated expression of the same four transcription factors (Oct4, Sox2, cMyc, Klf4). However, instead of using Fbx15 to select for pluripotent cells, the researchers used Nanog, a gene that is functionally important in ESCs. By using this different strategy, the researchers created iPSCs that were functionally identical to ESCs.[13] [14] [15] [16]

Human induced pluripotent stem cells

Generation from human fibroblasts

Reprogramming of human cells to iPSCs was reported in November 2007 by two independent research groups: Shinya Yamanaka of Kyoto University, Japan, who pioneered the original iPSC method, and James Thomson of University of Wisconsin-Madison who was the first to derive human embryonic stem cells. With the same principle used in mouse reprogramming, Yamanaka's group successfully transformed human fibroblasts into iPSCs with the same four pivotal genes, Oct4, Sox2, Klf4, and cMyc, using a retroviral system,[17] while Thomson and colleagues used a different set of factors, Oct4, Sox2, Nanog, and Lin28, using a lentiviral system.[18]

Generation from additional cell types

Obtaining fibroblasts to produce iPSCs involves a skin biopsy, and there has been a push towards identifying cell types that are more easily accessible.[19] [20] In 2008, iPSCs were derived from human keratinocytes, which could be obtained from a single hair pluck.[21] [22] In 2010, iPSCs were derived from peripheral blood cells,[23] [24] and in 2012, iPSCs were made from renal epithelial cells in the urine.[25]

Other considerations for starting cell type include mutational load (for example, skin cells may harbor more mutations due to UV exposure),[19] [20] time it takes to expand the population of starting cells,[19] and the ability to differentiate into a given cell type.[26]

Genes used to produce iPSCs

The generation of induced pluripotent cells is crucially dependent on the transcription factors used for the induction.

Oct-3/4 and certain products of the Sox gene family (Sox1, Sox2, Sox3, and Sox15) have been identified as crucial transcriptional regulators involved in the induction process whose absence makes induction impossible. Additional genes, however, including certain members of the Klf family (Klf1, Klf2, Klf4, and Klf5), the Myc family (c-myc, L-myc, and N-myc), Nanog, and LIN28, have been identified to increase the induction efficiency.

Challenges in reprogramming cells to pluripotency

Although the methods pioneered by Yamanaka and others have demonstrated that adult cells can be reprogrammed to iPS cells, there are still challenges associated with this technology:

  1. Low efficiency: in general, the conversion to iPS cells has been incredibly low. For example, the rate at which somatic cells were reprogrammed into iPS cells in Yamanaka's original mouse study was 0.01–0.1%.[1] The low efficiency rate may reflect the need for precise timing, balance, and absolute levels of expression of the reprogramming genes. It may also suggest a need for rare genetic or epigenetic changes in the original somatic cell population or in the prolonged culture. However, recently a path was found for efficient reprogramming which required downregulation of the nucleosome remodeling and deacetylation (NuRD) complex. Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs. Depletion of Mbd3, on the other hand, improves reprogramming efficiency,[32] that results in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells).[33]
  2. Genomic Insertion: genomic integration of the transcription factors limits the utility of the transcription factor approach because of the risk of mutations being inserted into the target cell's genome.[34] A common strategy for avoiding genomic insertion has been to use a different vector for input. Plasmids, adenoviruses, and transposon vectors have all been explored, but these often come with the tradeoff of lower throughput.[35] [36] [37]
  3. Tumorigenicity: Depending on the methods used, reprogramming of adult cells to obtain iPSCs may pose significant risks that could limit their use in humans. For example, if viruses are used to genomically alter the cells, the expression of oncogenes (cancer-causing genes) may potentially be triggered. In February 2008, scientists announced the discovery of a technique that could remove oncogenes after the induction of pluripotency, thereby increasing the potential use of iPS cells in human diseases.[38] In another study, Yamanaka reported that one can create iPSCs without the oncogene c-Myc. The process took longer and was not as efficient, but the resulting chimeras did not develop cancer.[39] Inactivation or deletion of the tumor suppressor p53, which is a key regulator of cancer, significantly increases reprogramming efficiency.[40] Thus there seems to be a tradeoff between reprogramming efficiency and tumor generation.
  4. Incomplete reprogramming: reprogramming also faces the challenge of completeness. This is particularly challenging because the genome-wide epigenetic code must be reformatted to that of the target cell type in order to fully reprogram a cell. However, three separate groups were able to find mouse embryonic fibroblast (MEF)-derived iPS cells that could be injected into tetraploid blastocysts and resulted in the live birth of mice derived entirely from iPS cells, thus ending the debate over the equivalence of embryonic stem cells (ESCs) and iPS with regard to pluripotency.[41]

The table on the right summarizes the key strategies and techniques used to develop iPS cells in the first five years after Yamanaka et al.'s 2006 breakthrough. Rows of similar colors represent studies that used similar strategies for reprogramming.

Alternative approaches

Mimicking transcription factors with chemicals

One of the main strategies for avoiding problems (1) and (2) has been to use small molecules that can mimic the effects of transcription factors. These compounds can compensate for a reprogramming factor that does not effectively target the genome or fails at reprogramming for another reason; thus they raise reprogramming efficiency. They also avoid the problem of genomic integration, which in some cases contributes to tumor genesis. Key studies using such strategy were conducted in 2008. Melton et al. studied the effects of histone deacetylase (HDAC) inhibitor valproic acid. They found that it increased reprogramming efficiency 100-fold (compared to Yamanaka's traditional transcription factor method).[42] The researchers proposed that this compound was mimicking the signaling that is usually caused by the transcription factor c-Myc. A similar type of compensation mechanism was proposed to mimic the effects of Sox2. In 2008, Ding et al. used the inhibition of histone methyl transferase (HMT) with BIX-01294 in combination with the activation of calcium channels in the plasma membrane in order to increase reprogramming efficiency. Deng et al. of Beijing University reported in July 2013 that induced pluripotent stem cells can be created without any genetic modification. They used a cocktail of seven small-molecule compounds including DZNep to induce the mouse somatic cells into stem cells which they called CiPS cells with the efficiency – at 0.2% – comparable to those using standard iPSC production techniques. The CiPS cells were introduced into developing mouse embryos and were found to contribute to all major cells types, proving its pluripotency.[43] [44]

Ding et al. demonstrated an alternative to transcription factor reprogramming through the use of drug-like chemicals. By studying the mesenchymal-epithelial transition (MET) process in which fibroblasts are pushed to a stem-cell like state, Ding's group identified two chemicals – ALK5 inhibitor SB431412 and MEK (mitogen-activated protein kinase) inhibitor PD0325901 – which was found to increase the efficiency of the classical genetic method by 100 fold. Adding a third compound known to be involved in the cell survival pathway, thiazovivin further increases the efficiency by 200 fold. Using the combination of these three compounds also decreased the reprogramming process of the human fibroblasts from four weeks to two weeks.[45] [46]

In April 2009, it was demonstrated that generation of iPS cells is possible without any genetic alteration of the adult cell: a repeated treatment of the cells with certain proteins channeled into the cells via poly-arginine anchors was sufficient to induce pluripotency.[47] The acronym given for those iPSCs is piPSCs (protein-induced pluripotent stem cells).

Alternate vectors

Another key strategy for avoiding problems such as tumorgenesis and low throughput has been to use alternate forms of vectors: adenoviruses, plasmids, and naked DNA or protein compounds.

In 2008, Hochedlinger et al. used an adenovirus to transport the requisite four transcription factors into the DNA of skin and liver cells of mice, resulting in cells identical to ESCs. The adenovirus is unique from other vectors like viruses and retroviruses because it does not incorporate any of its own genes into the targeted host and avoids the potential for insertional mutagenesis.[48] In 2009, Freed et al. demonstrated successful reprogramming of human fibroblasts to iPS cells.[49] Another advantage of using adenoviruses is that they only need to present for a brief amount of time in order for effective reprogramming to take place.

Also in 2008, Yamanaka et al. found that they could transfer the four necessary genes with a plasmid.[35] The Yamanaka group successfully reprogrammed mouse cells by transfection with two plasmid constructs carrying the reprogramming factors; the first plasmid expressed c-Myc, while the second expressed the other three factors (Oct4, Klf4, and Sox2). Although the plasmid methods avoid viruses, they still require cancer-promoting genes to accomplish reprogramming. The other main issue with these methods is that they tend to be much less efficient compared to retroviral methods. Furthermore, transfected plasmids have been shown to integrate into the host genome and therefore they still pose the risk of insertional mutagenesis. Because non-retroviral approaches have demonstrated such low efficiency levels, researchers have attempted to effectively rescue the technique with what is known as the PiggyBac Transposon System. Several studies have demonstrated that this system can effectively deliver the key reprogramming factors without leaving footprint mutations in the host cell genome. The PiggyBac Transposon System involves the re-excision of exogenous genes, which eliminates the issue of insertional mutagenesis.

Stimulus-triggered acquisition of pluripotency cell

See main article: Stimulus-triggered acquisition of pluripotency. In January 2014, two articles were published claiming that a type of pluripotent stem cell can be generated by subjecting the cells to certain types of stress (bacterial toxin, a low pH of 5.7, or physical squeezing); the resulting cells were called STAP cells, for stimulus-triggered acquisition of pluripotency.[50]

In light of difficulties that other labs had replicating the results of the surprising study, in March 2014, one of the co-authors has called for the articles to be retracted.[51] On 4 June 2014, the lead author, Obokata agreed to retract both the papers[52] after she was found to have committed 'research misconduct' as concluded in an investigation by RIKEN on 1 April 2014.[53]

RNA molecules

MicroRNAs are short RNA molecules that bind to complementary sequences on messenger RNA and block expression of a gene. Measuring variations in microRNA expression in iPS cells can be used to predict their differentiation potential.[54] Addition of microRNAs can also be used to enhance iPS potential. Several mechanisms have been proposed. ES cell-specific microRNA molecules (such as miR-291, miR-294 and miR-295) enhance the efficiency of induced pluripotency by acting downstream of c-Myc.[55] MicroRNAs can also block expression of repressors of Yamanaka's four transcription factors, and there may be additional mechanisms induce reprogramming even in the absence of added exogenous transcription factors.

Identity

Induced pluripotent stem cells are similar to natural pluripotent stem cells, such as embryonic stem cells, in many aspects, such as the expression of certain stem cell genes and proteins, chromatin methylation patterns, doubling time, embryoid body formation, teratoma formation, viable chimera formation, and potency and differentiability, but the full extent of their relation to natural pluripotent stem cells is still being assessed.[1]

Gene expression and genome-wide H3K4me3 and H3K27me3 were found to be extremely similar between ES and iPS cells.[56] The generated iPSCs were remarkably similar to naturally isolated pluripotent stem cells (such as mouse and human embryonic stem cells, mESCs and hESCs, respectively) in the following respects, thus confirming the identity, authenticity, and pluripotency of iPSCs to naturally isolated pluripotent stem cells:

Safety

Medical research

The task of producing iPS cells continues to be challenging due to the six problems mentioned above. A key tradeoff to overcome is that between efficiency and genomic integration. Most methods that do not rely on the integration of transgenes are inefficient, while those that do rely on the integration of transgenes face the problems of incomplete reprogramming and tumor genesis, although a vast number of techniques and methods have been attempted. Another large set of strategies is to perform a proteomic characterization of iPS cells.[66] Further studies and new strategies should generate optimal solutions to the five main challenges. One approach might attempt to combine the positive attributes of these strategies into an ultimately effective technique for reprogramming cells to iPS cells.

Another approach is the use of iPS cells derived from patients to identify therapeutic drugs able to rescue a phenotype. For instance, iPS cell lines derived from patients affected by ectodermal dysplasia syndrome (EEC), in which the p63 gene is mutated, display abnormal epithelial commitment that could be partially rescued by a small compound.[67]

Disease modeling and drug development

An attractive feature of human iPS cells is the ability to derive them from adult patients to study the cellular basis of human disease. Since iPS cells are self-renewing and pluripotent, they represent a theoretically unlimited source of patient-derived cells which can be turned into any type of cell in the body. This is particularly important because many other types of human cells derived from patients tend to stop growing after a few passages in laboratory culture. iPS cells have been generated for a wide variety of human genetic diseases, including common disorders such as Down syndrome and polycystic kidney disease.[68] [69] [70] In many instances, the patient-derived iPS cells exhibit cellular defects not observed in iPS cells from healthy subjects, providing insight into the pathophysiology of the disease.[71] [72] An international collaborated project, StemBANCC, was formed in 2012 to build a collection of iPS cell lines for drug screening for a variety of diseases. Managed by the University of Oxford, the effort pooled funds and resources from 10 pharmaceutical companies and 23 universities. The goal is to generate a library of 1,500 iPS cell lines which will be used in early drug testing by providing a simulated human disease environment.[73] Furthermore, combining hiPSC technology and small molecule or genetically encoded voltage and calcium indicators provided a large-scale and high-throughput platform for cardiovascular drug safety screening.[74] [75] [76] [77] [78]

Organ synthesis

A proof-of-concept of using induced pluripotent stem cells (iPSCs) to generate human organ for transplantation was reported by researchers from Japan. Human 'liver buds' (iPSC-LBs) were grown from a mixture of three different kinds of stem cells: hepatocyte (for liver function) coaxed from iPSCs; endothelial stem cells (to form lining of blood vessels) from umbilical cord blood; and mesenchymal stem cells (to form connective tissue). This new approach allows different cell types to self-organize into a complex organ, mimicking the process in fetal development. After growing in vitro for a few days, the liver buds were transplanted into mice where the 'liver' quickly connected with the host blood vessels and continued to grow. Most importantly, it performed regular liver functions including metabolizing drugs and producing liver-specific proteins. Further studies will monitor the longevity of the transplanted organ in the host body (ability to integrate or avoid rejection) and whether it will transform into tumors.[79] [80]

Organ regeneration

In 2021, a switchable Yamanaka factors-reprogramming-based approach for regeneration of damaged heart without tumor-formation was demonstrated in mice and was successful if the intervention was carried out immediately before or after a heart attack.[81]

Tissue repair

Embryonic cord-blood cells were induced into pluripotent stem cells using plasmid DNA. Using cell surface endothelial/pericytic markers CD31 and CD146, researchers identified 'vascular progenitor', the high-quality, multipotent vascular stem cells. After the iPS cells were injected directly into the vitreous of the damaged retina of mice, the stem cells engrafted into the retina, grew and repaired the vascular vessels.[82] [83]

Labelled iPSCs-derived NSCs injected into laboratory animals with brain lesions were shown to migrate to the lesions and some motor function improvement was observed.[84]

Cardiomyocytes

Beating cardiac muscle cells, iPSC-derived cardiomyocytes, can be mass-produced using chemically defined differentiation protocols.[85] [86] These protocols typically modulate the same developmental signaling pathways required for heart development.[87] These iPSC-cardiomyocytes can recapitulate genetic arrhythmias and cardiac drug responses, since they exhibit the same genetic background as the patient from which they were derived.[88] [89] [90] [91]

In June 2014, Takara Bio received technology transfer from iHeart Japan, a venture company from Kyoto University's iPS Cell Research Institute, to make it possible to exclusively use technologies and patents that induce differentiation of iPS cells into cardiomyocytes in Asia. The company announced the idea of selling cardiomyocytes to pharmaceutical companies and universities to help develop new drugs for heart disease.[92]

On March 9, 2018, the Specified Regenerative Medicine Committee of Osaka University officially approved the world's first clinical research plan to transplant a "myocardial sheet" made from iPS cells into the heart of patients with severe heart failure. Osaka University announced that it had filed an application with the Ministry of Health, Labor and Welfare on the same day.

On May 16, 2018, the clinical research plan was approved by the Ministry of Health, Labor and Welfare's expert group with a condition.[93] [94]

In October 2019, a group at Okayama University developed a model of ischemic heart disease using cardiomyocytes differentiated from iPS cells.[95]

Red blood cells

Although a pint of donated blood contains about two trillion red blood cells and over 107 million blood donations are collected globally, there is still a critical need for blood for transfusion. In 2014, type O red blood cells were synthesized at the Scottish National Blood Transfusion Service from iPSC. The cells were induced to become a mesoderm and then blood cells and then red blood cells. The final step was to make them eject their nuclei and mature properly. Type O can be transfused into all patients. Human clinical trials were not expected to begin before 2016.[96]

Clinical trial

The first human clinical trial using autologous iPSCs was approved by the Japan Ministry Health and was to be conducted in 2014 at the Riken Center for Developmental Biology in Kobe. However the trial was suspended after Japan's new regenerative medicine laws came into effect in November 2015.[97] More specifically, an existing set of guidelines was strengthened to have the force of law (previously mere recommendations).[98] iPSCs derived from skin cells from six patients with wet age-related macular degeneration were reprogrammed to differentiate into retinal pigment epithelial (RPE) cells. The cell sheet would be transplanted into the affected retina where the degenerated RPE tissue was excised. Safety and vision restoration monitoring were to last one to three years.[99] [100]

In March 2017, a team led by Masayo Takahashi completed the first successful transplant of iPS-derived retinal cells from a donor into the eye of a person with advanced macular degeneration.[101] However it was reported that they are now having complications.[102] The benefits of using autologous iPSCs are that there is theoretically no risk of rejection and that it eliminates the need to use embryonic stem cells. However, these iPSCs were derived from another person.[100]

New clinical trials involving iPSCs are now ongoing not only in Japan, but also in the US and Europe.[103] Research in 2021 on the trial registry Clinicaltrials.gov identified 129 trial listings mentioning iPSCs, but most were non-interventional.[104]

Strategy for obtaining universal iPSCs

To make iPSC-based regenerative medicine technologies available to more patients, it is necessary to create universal iPSCs that can be transplanted independently of haplotypes of HLA. The current strategy for the creation of universal iPSCs has two main goals: to remove HLA expression and to prevent NK cells attacks due to deletion of HLA. Deletion of the B2M and CIITA genes using the CRISPR/Cas9 system has been reported to suppress the expression of HLA class I and class II, respectively. To avoid NK cell attacks. transduction of ligands inhibiting NK-cells, such as HLA-E and CD47 has been used.[105] HLA-C is left unchanged, since the 12 common HLA-C alleles are enough to cover 95% of the world's population.

Anti-aging properties

A multipotent mesenchymal stem cell, when induced into pluripotence, holds great promise to slow or reverse aging phenotypes. Such anti-aging properties were demonstrated in early clinical trials in 2017.[106] In 2020, Stanford University researchers concluded after studying elderly mice that old human cells when subjected to the Yamanaka factors, might rejuvenate and become nearly indistinguishable from their younger counterparts.[107]

See also

External links

Notes and References

  1. Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors . Cell . 126 . 4 . 663–76 . August 2006 . 16904174 . 10.1016/j.cell.2006.07.024 . free . 2433/159777 . free .
  2. Web site: The Nobel Prize in Physiology or Medicine – 2012 Press Release. Nobel Media AB. 8 October 2012.
  3. Mahla RS . Stem Cells Applications in Regenerative Medicine and Disease Therapeutics . International Journal of Cell Biology . 2016 . 6940283 . 2016 . 27516776 . 4969512 . 10.1155/2016/6940283 . free .
  4. Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R . Human embryonic stem cell lines derived from single blastomeres . Nature . 444 . 7118 . 481–5 . November 2006 . 16929302 . 10.1038/nature05142 . 2006Natur.444..481K . 84792371 .
  5. Hockemeyer D, Jaenisch R . Induced Pluripotent Stem Cells Meet Genome Editing . Cell Stem Cell . 18 . 5 . 573–86 . May 2016 . 27152442 . 4871596 . 10.1016/j.stem.2016.04.013 .
  6. News: 「i」PSなぜ小文字？ 山中さんってどんな人？. 朝日新聞. 2012-10-08. 2013-04-27. 21 November 2012. https://web.archive.org/web/20121121094358/http://www.asahi.com/science/update/1008/OSK201210080032.html. dead.
  7. News: 万能なiPS細胞「iPodのように普及してほしい」. スポーツニッポン. 2012-10-09. 2012-10-14.
  8. News: 山中教授の「iPS細胞」ってiPod のパクリ!?流行らせたいと頭小文字. J-CASTニュース. 2012-10-09. 2013-04-28.
  9. Eguizabal C, Aran B, Chuva de Sousa Lopes SM, Geens M, Heindryckx B, Panula S, Popovic M, Vassena R, Veiga A . Two decades of embryonic stem cells: a historical overview . Human Reproduction Open . 2019 . 2019 . 1 . hoy024 . 10.1093/hropen/hoy024 . free . 30895264 . 6396646 .
  10. Yamanaka S . The winding road to pluripotency (Nobel Lecture) . Angewandte Chemie . 52 . 52 . 13900–9 . December 2013 . 24255017 . 10.1002/anie.201306721 .
  11. Guo XL, Chen JS . Research on induced pluripotent stem cells and the application in ocular tissues . International Journal of Ophthalmology . 8 . 4 . 818–25 . 2015 . 26309885 . 4539634 . 10.3980/j.issn.2222-3959.2015.04.31 .
  12. Thornton . Christopher D. . Fielding . Stuart . Karbowniczek . Kinga . Roig-Merino . Alicia . Burrows . Alysha E. . FitzPatrick . Lorna M. . Sharaireh . Aseel . Tite . John P. . Mole . Sara E. . Harbottle . Richard P. . Caproni . Lisa J. . McKay . Tristan R. . 2021-12-10 . Safe and stable generation of induced pluripotent stem cells using doggybone DNA vectors . Molecular Therapy - Methods & Clinical Development . English . 23 . 348–358 . 10.1016/j.omtm.2021.09.018 . 2329-0501 . 8546411 . 34729381.
  13. Okita K, Ichisaka T, Yamanaka S . Generation of germline-competent induced pluripotent stem cells . Nature . 448 . 7151 . 313–7 . July 2007 . 17554338 . 10.1038/nature05934 . 2007Natur.448..313O . 459050 .
  14. Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R . 6 . In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state . Nature . 448 . 7151 . 318–24 . July 2007 . 17554336 . 10.1038/nature05944 . 2007Natur.448..318W . 4377572 .
  15. Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K . 6 . Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution . Cell Stem Cell . 1 . 1 . 55–70 . June 2007 . 18371336 . 10.1016/j.stem.2007.05.014 . free .
  16. Web site: Generations of iPSCs and related references. 5 November 2007. 30 June 2018. https://web.archive.org/web/20180630162001/http://sbaminbeta.blogspot.com/2007/08/reprogramming-cell-part-4-ips.html. dead.
  17. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S . Induction of pluripotent stem cells from adult human fibroblasts by defined factors . Cell . 131 . 5 . 861–72 . November 2007 . 18035408 . 10.1016/j.cell.2007.11.019 . free . 2433/49782 . free .
  18. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA . 6 . Induced pluripotent stem cell lines derived from human somatic cells . Science . 318 . 5858 . 1917–20 . December 2007 . 18029452 . 10.1126/science.1151526 . 2007Sci...318.1917Y . 86129154 .
  19. Yamanaka S . Patient-specific pluripotent stem cells become even more accessible . Cell Stem Cell . 7 . 1 . 1–2 . July 2010 . 20621038 . 10.1016/j.stem.2010.06.009 . free .
  20. Maherali N, Hochedlinger K . Guidelines and techniques for the generation of induced pluripotent stem cells . Cell Stem Cell . 3 . 6 . 595–605 . December 2008 . 19041776 . 10.1016/j.stem.2008.11.008 . free .
  21. Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K . A high-efficiency system for the generation and study of human induced pluripotent stem cells . Cell Stem Cell . 3 . 3 . 340–5 . September 2008 . 18786420 . 3987901 . 10.1016/j.stem.2008.08.003 .
  22. Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, Vassena R, Bilić J, Pekarik V, Tiscornia G, Edel M, Boué S, Izpisúa Belmonte JC . 6 . Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes . Nature Biotechnology . 26 . 11 . 1276–84 . November 2008 . 18931654 . 10.1038/nbt.1503 . 205274019 .
  23. Staerk J, Dawlaty MM, Gao Q, Maetzel D, Hanna J, Sommer CA, Mostoslavsky G, Jaenisch R . 6 . Reprogramming of human peripheral blood cells to induced pluripotent stem cells . Cell Stem Cell . 7 . 1 . 20–4 . July 2010 . 20621045 . 2917234 . 10.1016/j.stem.2010.06.002 .
  24. Loh YH, Hartung O, Li H, Guo C, Sahalie JM, Manos PD, Urbach A, Heffner GC, Grskovic M, Vigneault F, Lensch MW, Park IH, Agarwal S, Church GM, Collins JJ, Irion S, Daley GQ . 6 . Reprogramming of T cells from human peripheral blood . Cell Stem Cell . 7 . 1 . 15–9 . July 2010 . 20621044 . 2913590 . 10.1016/j.stem.2010.06.004 .
  25. Zhou T, Benda C, Dunzinger S, Huang Y, Ho JC, Yang J, Wang Y, Zhang Y, Zhuang Q, Li Y, Bao X, Tse HF, Grillari J, Grillari-Voglauer R, Pei D, Esteban MA . 6 . Generation of human induced pluripotent stem cells from urine samples . Nature Protocols . 7 . 12 . 2080–9 . December 2012 . 23138349 . 10.1038/nprot.2012.115 . 205465442 .
  26. Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, Apostolou E, Stadtfeld M, Li Y, Shioda T, Natesan S, Wagers AJ, Melnick A, Evans T, Hochedlinger K . 6 . Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells . Nature Biotechnology . 28 . 8 . 848–55 . August 2010 . 20644536 . 3148605 . 10.1038/nbt.1667 .
  27. Velychko S, Adachi K, Kim KP, Hou Y, MacCarthy CM, Wu G, Schöler HR . Excluding Oct4 from Yamanaka Cocktail Unleashes the Developmental Potential of iPSCs . Cell Stem Cell . 25 . 6 . 737–753.e4 . December 2019 . 31708402 . 6900749 . 10.1016/j.stem.2019.10.002 .
  28. https://www.mpi-muenster.mpg.de/520372/20191107-better-reprogramming-by-omitting-oct4 Quality of induced pluripotent stem cells is dramatically enhanced by omitting what was thought to be the most crucial reprogramming factor
  29. MacCarthy . Caitlin M. . Wu . Guangming . Malik . Vikas . Menuchin-Lasowski . Yotam . Velychko . Taras . Keshet . Gal . Fan . Rui . Bedzhov . Ivan . Church . George M. . Jauch . Ralf . Cojocaru . Vlad . Schöler . Hans R. . Velychko . Sergiy . Highly cooperative chimeric super-SOX induces naive pluripotency across species . Cell Stem Cell . December 2023 . 31 . 1 . 127–147.e9 . 10.1016/j.stem.2023.11.010. free . 38141611 .
  30. Ali PS, Ghoshdastider U, Hoffmann J, Brutschy B, Filipek S . Recognition of the let-7g miRNA precursor by human Lin28B . FEBS Letters . 586 . 22 . 3986–90 . November 2012 . 23063642 . 10.1016/j.febslet.2012.09.034 . 28899778 . free . 2012FEBSL.586.3986S .
  31. Maekawa M, Yamaguchi K, Nakamura T, Shibukawa R, Kodanaka I, Ichisaka T, Kawamura Y, Mochizuki H, Goshima N, Yamanaka S . 6 . Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1 . Nature . 474 . 7350 . 225–9 . June 2011 . 21654807 . 10.1038/nature10106 . free . 2433/141930 . 4428172 .
  32. Luo M, Ling T, Xie W, Sun H, Zhou Y, Zhu Q, Shen M, Zong L, Lyu G, Zhao Y, Ye T, Gu J, Tao W, Lu Z, Grummt I . 6 . NuRD blocks reprogramming of mouse somatic cells into pluripotent stem cells . Stem Cells . 31 . 7 . 1278–86 . July 2013 . 23533168 . 10.1002/stem.1374 . 10397/18487 . 206512562 . free .
  33. Rais Y, Zviran A, Geula S, Gafni O, Chomsky E, Viukov S, Mansour AA, Caspi I, Krupalnik V, Zerbib M, Maza I, Mor N, Baran D, Weinberger L, Jaitin DA, Lara-Astiaso D, Blecher-Gonen R, Shipony Z, Mukamel Z, Hagai T, Gilad S, Amann-Zalcenstein D, Tanay A, Amit I, Novershtern N, Hanna JH . 6 . Deterministic direct reprogramming of somatic cells to pluripotency . Nature . 502 . 7469 . 65–70 . October 2013 . 24048479 . 10.1038/nature12587 . 2013Natur.502...65R . 4386833 .
  34. Selvaraj V, Plane JM, Williams AJ, Deng W . Switching cell fate: the remarkable rise of induced pluripotent stem cells and lineage reprogramming technologies . Trends in Biotechnology . 28 . 4 . 214–23 . April 2010 . 20149468 . 2843790 . 10.1016/j.tibtech.2010.01.002 .
  35. Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S . Generation of mouse induced pluripotent stem cells without viral vectors . Science . 322 . 5903 . 949–53 . November 2008 . 18845712 . 10.1126/science.1164270 . 2008Sci...322..949O . 23735743 . free .
  36. Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K . Induced pluripotent stem cells generated without viral integration . Science . 322 . 5903 . 945–9 . November 2008 . 18818365 . 3987909 . 10.1126/science.1162494 . 2008Sci...322..945S .
  37. Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hämäläinen R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A . 6 . piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells . Nature . 458 . 7239 . 766–70 . April 2009 . 19252478 . 3758996 . 10.1038/nature07863 . 2009Natur.458..766W .
  38. News: Cancer threat removed from stem cells, scientists say . Los Angeles Times . Kaplan K . 2009-03-06.
  39. Web site: Swaminathan N . Stem Cells – This Time Without the Cancer. Scientific American News. 2007-12-11. 2007-11-30.
  40. Marión RM, Strati K, Li H, Murga M, Blanco R, Ortega S, Fernandez-Capetillo O, Serrano M, Blasco MA . 6 . A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity . Nature . 460 . 7259 . 1149–53 . August 2009 . 19668189 . 3624089 . 10.1038/nature08287 . 2009Natur.460.1149M .
  41. Zhao XY, Li W, Lv Z, Liu L, Tong M, Hai T, Hao J, Guo CL, Ma QW, Wang L, Zeng F, Zhou Q . 6 . iPS cells produce viable mice through tetraploid complementation . Nature . 461 . 7260 . 86–90 . September 2009 . 19672241 . 10.1038/nature08267 . 2009Natur.461...86Z . 205217762 .
  42. Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA . Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds . Nature Biotechnology . 26 . 7 . 795–7 . July 2008 . 18568017 . 6334647 . 10.1038/nbt1418 .
  43. Stem cells reprogrammed using chemicals alone. Nature News. Cyranoski D . 18 July 2013. 10.1038/nature.2013.13416. 88247014. 22 July 2013.
  44. Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, Zhao T, Ye J, Yang W, Liu K, Ge J, Xu J, Zhang Q, Zhao Y, Deng H . 6 . Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds . Science . 341 . 6146 . 651–4 . August 2013 . 23868920 . 10.1126/science.1239278 . 2013Sci...341..651H . 45685692 .
  45. Web site: Major Step In Making Better Stem Cells From Adult Tissue . Science Daily . 19 October 2009 . 30 September 2013.
  46. Lin T, Ambasudhan R, Yuan X, Li W, Hilcove S, Abujarour R, Lin X, Hahm HS, Hao E, Hayek A, Ding S . 6 . A chemical platform for improved induction of human iPSCs . Nature Methods . 6 . 11 . 805–8 . November 2009 . 19838168 . 3724527 . 10.1038/nmeth.1393 .
  47. Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y, Siuzdak G, Schöler HR, Duan L, Ding S . 6 . Generation of induced pluripotent stem cells using recombinant proteins . Cell Stem Cell . 4 . 5 . 381–4 . May 2009 . 19398399 . 10.1016/j.stem.2009.04.005 . 10182564 . free . Gary Siuzdak .
  48. Shi Y, Desponts C, Do JT, Hahm HS, Schöler HR, Ding S . Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds . Cell Stem Cell . 3 . 5 . 568–74 . November 2008 . 18983970 . 10.1016/j.stem.2008.10.004 . free .
  49. Zhou W, Freed CR . Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells . Stem Cells . 27 . 11 . 2667–74 . November 2009 . 19697349 . 10.1002/stem.201 . 41418742 . free .
  50. David Cyranoski for Nature News. January 29, 2014 Acid bath offers easy path to stem cells
  51. Tracy Vence for the Scientist. March 11, 2014 Call for STAP Retractions
  52. News: Japan researcher agrees to withdraw disputed stem cell paper. Lies E . Reuters. 4 June 2014. 4 June 2014.
  53. Web site: Report on STAP Cell Research Paper Investigation. Press Release. RIKEN. 1 April 2014. 2 June 2014.
  54. Bao X, Zhu X, Liao B, Benda C, Zhuang Q, Pei D, Qin B, Esteban MA . 6 . MicroRNAs in somatic cell reprogramming . Current Opinion in Cell Biology . 25 . 2 . 208–14 . April 2013 . 23332905 . 10.1016/j.ceb.2012.12.004 .
  55. Judson RL, Babiarz JE, Venere M, Blelloch R . Embryonic stem cell-specific microRNAs promote induced pluripotency . Nature Biotechnology . 27 . 5 . 459–61 . May 2009 . 19363475 . 2743930 . 10.1038/nbt.1535 .
  56. Guenther MG, Frampton GM, Soldner F, Hockemeyer D, Mitalipova M, Jaenisch R, Young RA . Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells . Cell Stem Cell . 7 . 2 . 249–57 . August 2010 . 20682450 . 3010384 . 10.1016/j.stem.2010.06.015 .
  57. Kang L, Wang J, Zhang Y, Kou Z, Gao S . iPS cells can support full-term development of tetraploid blastocyst-complemented embryos . Cell Stem Cell . 5 . 2 . 135–8 . August 2009 . 19631602 . 10.1016/j.stem.2009.07.001 . free .
  58. Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Antosiewicz-Bourget J, O'Malley R, Castanon R, Klugman S, Downes M, Yu R, Stewart R, Ren B, Thomson JA, Evans RM, Ecker JR . 6 . Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells . Nature . 471 . 7336 . 68–73 . March 2011 . 21289626 . 3100360 . 10.1038/nature09798 . 2011Natur.471...68L .
  59. Knoepfler PS . Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine . Stem Cells . 27 . 5 . 1050–6 . May 2009 . 19415771 . 2733374 . 10.1002/stem.37 .
  60. Nori S, Okada Y, Yasuda A, Tsuji O, Takahashi Y, Kobayashi Y, Fujiyoshi K, Koike M, Uchiyama Y, Ikeda E, Toyama Y, Yamanaka S, Nakamura M, Okano H . 6 . Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice . Proceedings of the National Academy of Sciences of the United States of America . 108 . 40 . 16825–30 . October 2011 . 21949375 . 3189018 . 10.1073/pnas.1108077108 . 2011PNAS..10816825N . free .
  61. Nori S, Okada Y, Nishimura S, Sasaki T, Itakura G, Kobayashi Y, Renault-Mihara F, Shimizu A, Koya I, Yoshida R, Kudoh J, Koike M, Uchiyama Y, Ikeda E, Toyama Y, Nakamura M, Okano H . 6 . Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model: oncogenic transformation with epithelial-mesenchymal transition . Stem Cell Reports . 4 . 3 . 360–73 . March 2015 . 25684226 . 4375796 . 10.1016/j.stemcr.2015.01.006 .
  62. Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, Chiba T, Yamanaka S . 6 . Generation of pluripotent stem cells from adult mouse liver and stomach cells . Science . 321 . 5889 . 699–702 . August 2008 . 18276851 . 10.1126/science.1154884 . 2008Sci...321..699A . free . 2433/124215 . 52869734 .
  63. Gutierrez-Aranda I, Ramos-Mejia V, Bueno C, Munoz-Lopez M, Real PJ, Mácia A, Sanchez L, Ligero G, Garcia-Parez JL, Menendez P . 6 . Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection . Stem Cells . 28 . 9 . 1568–70 . September 2010 . 20641038 . 2996086 . 10.1002/stem.471 .
  64. Zhao T, Zhang ZN, Rong Z, Xu Y . Immunogenicity of induced pluripotent stem cells . Nature . 474 . 7350 . 212–5 . May 2011 . 21572395 . 10.1038/nature10135 . 10.1.1.864.8029 . 4416964 .
  65. Araki R, Uda M, Hoki Y, Sunayama M, Nakamura M, Ando S, Sugiura M, Ideno H, Shimada A, Nifuji A, Abe M . 6 . Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells . Nature . 494 . 7435 . 100–4 . February 2013 . 23302801 . 10.1038/nature11807 . 2013Natur.494..100A . 205232231 .
  66. Boland MJ, Hazen JL, Nazor KL, Rodriguez AR, Gifford W, Martin G, Kupriyanov S, Baldwin KK . 6 . Adult mice generated from induced pluripotent stem cells . Nature . 461 . 7260 . 91–4 . September 2009 . 19672243 . 10.1038/nature08310 . 2009Natur.461...91B . 4423755 .
  67. Shalom-Feuerstein R, Serror L, Aberdam E, Müller FJ, van Bokhoven H, Wiman KG, Zhou H, Aberdam D, Petit I . 6 . Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET . Proceedings of the National Academy of Sciences of the United States of America . 110 . 6 . 2152–6 . February 2013 . 23355677 . 3568301 . 10.1073/pnas.1201753109 . 2013PNAS..110.2152S . free .
  68. Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ . 6 . Disease-specific induced pluripotent stem cells . Cell . 134 . 5 . 877–86 . September 2008 . 18691744 . 2633781 . 10.1016/j.cell.2008.07.041 .
  69. Freedman BS, Lam AQ, Sundsbak JL, Iatrino R, Su X, Koon SJ, Wu M, Daheron L, Harris PC, Zhou J, Bonventre JV . 6 . Reduced ciliary polycystin-2 in induced pluripotent stem cells from polycystic kidney disease patients with PKD1 mutations . Journal of the American Society of Nephrology . 24 . 10 . 1571–86 . October 2013 . 24009235 . 3785271 . 10.1681/ASN.2012111089 .
  70. Dolmetsch R, Geschwind D . The human brain in a dish: the promise of iPSC-derived neurons. . Cell . 145 . 6 . 831–4 . Jun 2011 . 21663789 . 10.1016/j.cell.2011.05.034 . free . 3691069 .
  71. Grskovic M, Javaherian A, Strulovici B, Daley GQ . Induced pluripotent stem cells--opportunities for disease modeling and drug discovery . Nature Reviews. Drug Discovery . 10 . 12 . 915–29 . November 2011 . 22076509 . 10.1038/nrd3577 . 7945956 .
  72. Shi Y, Inoue H, Wu JC, Yamanaka S . Induced pluripotent stem cell technology: a decade of progress. . Nat Rev Drug Discov . 16 . 2 . 115–30 . Feb 2017 . 27980341 . 10.1038/nrd.2016.245 . 6416143 .
  73. Web site: Roche, Pfizer, Sanofi Plan $72.7 Million Stem-Cell Bank. Gerlin A . Bloomberg.com. 5 December 2012. 23 December 2012.
  74. Shinnawi R, Huber I, Maizels L, Shaheen N, Gepstein A, Arbel G, Tijsen AJ, Gepstein L . 6 . Monitoring Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Genetically Encoded Calcium and Voltage Fluorescent Reporters . Stem Cell Reports . 5 . 4 . 582–96 . October 2015 . 26372632 . 4624957 . 10.1016/j.stemcr.2015.08.009 .
  75. Shaheen N, Shiti A, Huber I, Shinnawi R, Arbel G, Gepstein A, Setter N, Goldfracht I, Gruber A, Chorna SV, Gepstein L . 6 . Human Induced Pluripotent Stem Cell-Derived Cardiac Cell Sheets Expressing Genetically Encoded Voltage Indicator for Pharmacological and Arrhythmia Studies . Stem Cell Reports . 10 . 6 . 1879–1894 . June 2018 . 29754959 . 5989818 . 10.1016/j.stemcr.2018.04.006 .
  76. Sharma . Arun . Burridge . Paul W. . McKeithan . Wesley L. . Serrano . Ricardo . Shukla . Praveen . Sayed . Nazish . Churko . Jared M. . Kitani . Tomoya . Wu . Haodi . Holmström . Alexandra . Matsa . Elena . 2017-02-15 . High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells . Science Translational Medicine . 9 . 377 . eaaf2584 . 10.1126/scitranslmed.aaf2584 . 1946-6242 . 5409837 . 28202772.
  77. McKeithan . Wesley L. . Savchenko . Alex . Yu . Michael S. . Cerignoli . Fabio . Bruyneel . Arne A. N. . Price . Jeffery H. . Colas . Alexandre R. . Miller . Evan W. . Cashman . John R. . Mercola . Mark . 2017 . An Automated Platform for Assessment of Congenital and Drug-Induced Arrhythmia with hiPSC-Derived Cardiomyocytes . Frontiers in Physiology . 8 . 766 . 10.3389/fphys.2017.00766 . 1664-042X . 5641590 . 29075196. free .
  78. Serrano . Ricardo . Feyen . Dries A.M. . Bruyneel . Arne A.N. . Hnatiuk . Anna P. . Vu . Michelle M. . Amatya . Prashila L. . Perea-Gil . Isaac . Prado . Maricela . Seeger . Timon . Wu . Joseph C. . Karakikes . Ioannis . Mercola . Mark . January 2023 . A deep learning platform to assess drug proarrhythmia risk . Cell Stem Cell . en . 30 . 1 . 86–95.e4 . 10.1016/j.stem.2022.12.002. 36563695 . 9924077 .
  79. Miniature human liver grown in mice. Nature. Baker M . 3 July 2013. 19 July 2013. 10.1038/nature.2013.13324. 87064973.
  80. Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguchi H . 6 . Vascularized and functional human liver from an iPSC-derived organ bud transplant . Nature . 499 . 7459 . 481–4 . July 2013 . 23823721 . 10.1038/nature12271 . 2013Natur.499..481T . 4423004 .
  81. Chen Y, Lüttmann FF, Schoger E, Schöler HR, Zelarayán LC, Kim KP, Haigh JJ, Kim J, Braun T . 6 . Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice . Science . 373 . 6562 . 1537–1540 . September 2021 . 34554778 . 10.1126/science.abg5159 . 2021Sci...373.1537C . 237617229 .
  82. Web site: Researchers repair retinas in mice with virus-free stem cells. Mullin E . fiercebiotech.com. 28 January 2014. 17 February 2014.
  83. Park TS, Bhutto I, Zimmerlin L, Huo JS, Nagaria P, Miller D, Rufaihah AJ, Talbot C, Aguilar J, Grebe R, Merges C, Reijo-Pera R, Feldman RA, Rassool F, Cooke J, Lutty G, Zambidis ET . 6 . Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature . Circulation . 129 . 3 . 359–72 . January 2014 . 24163065 . 4090244 . 10.1161/CIRCULATIONAHA.113.003000 .
  84. Tang H, Sha H, Sun H, Wu X, Xie L, Wang P, Xu C, Larsen C, Zhang HL, Gong Y, Mao Y, Chen X, Zhou L, Feng X, Zhu J . 6 . Tracking induced pluripotent stem cells-derived neural stem cells in the central nervous system of rats and monkeys . Cellular Reprogramming . 15 . 5 . 435–42 . October 2013 . 24020696 . 3787483 . 10.1089/cell.2012.0081 .
  85. Burridge PW, Matsa E, Shukla P, Lin ZC, Churko JM, Ebert AD, Lan F, Diecke S, Huber B, Mordwinkin NM, Plews JR, Abilez OJ, Cui B, Gold JD, Wu JC . 6 . Chemically defined generation of human cardiomyocytes . Nature Methods . 11 . 8 . 855–60 . August 2014 . 24930130 . 4169698 . 10.1038/nmeth.2999 .
  86. Feyen . Dries A. M. . McKeithan . Wesley L. . Bruyneel . Arne A. N. . Spiering . Sean . Hörmann . Larissa . Ulmer . Bärbel . Zhang . Hui . Briganti . Francesca . Schweizer . Michaela . Hegyi . Bence . Liao . Zhandi . 2020-07-21 . Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes . Cell Reports . 32 . 3 . 107925 . 10.1016/j.celrep.2020.107925 . 2211-1247 . 7437654 . 32697997.
  87. Willems E, Spiering S, Davidovics H, Lanier M, Xia Z, Dawson M, Cashman J, Mercola M . 6 . Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm . Circulation Research . 109 . 4 . 360–4 . August 2011 . 21737789 . 3327303 . 10.1161/CIRCRESAHA.111.249540 .
  88. Yazawa M, Hsueh B, Jia X, Pasca AM, Bernstein JA, Hallmayer J, Dolmetsch RE . Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome . Nature . 471 . 7337 . 230–4 . March 2011 . 21307850 . 10.1038/nature09855 . 3077925 . 2011Natur.471..230Y .
  89. Itzhaki I, Maizels L, Huber I, Zwi-Dantsis L, Caspi O, Winterstern A, Feldman O, Gepstein A, Arbel G, Hammerman H, Boulos M, Gepstein L . 6 . Modelling the long QT syndrome with induced pluripotent stem cells . Nature . 471 . 7337 . 225–9 . March 2011 . 21240260 . 10.1038/nature09747 . 2011Natur.471..225I . 4384573 .
  90. Sharma A, Burridge PW, McKeithan WL, Serrano R, Shukla P, Sayed N, Churko JM, Kitani T, Wu H, Holmström A, Matsa E, Zhang Y, Kumar A, Fan AC, Del Álamo JC, Wu SM, Moslehi JJ, Mercola M, Wu JC . 6 . High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells . Science Translational Medicine . 9 . 377 . eaaf2584 . February 2017 . 28202772 . 5409837 . 10.1126/scitranslmed.aaf2584 .
  91. McKeithan . Wesley L. . Feyen . Dries A. M. . Bruyneel . Arne A. N. . Okolotowicz . Karl J. . Ryan . Daniel A. . Sampson . Kevin J. . Potet . Franck . Savchenko . Alex . Gómez-Galeno . Jorge . Vu . Michelle . Serrano . Ricardo . 2020-11-05 . Reengineering an Antiarrhythmic Drug Using Patient hiPSC Cardiomyocytes to Improve Therapeutic Potential and Reduce Toxicity . Cell Stem Cell . 27 . 5 . 813–821.e6 . 10.1016/j.stem.2020.08.003 . 1875-9777 . 7655512 . 32931730.
  92. Web site: iPSから心筋細胞製造 タカラバイオとベンチャー. 日本経済新聞 電子版. 24 June 2014. ja. 2019-11-08.
  93. Web site: iPSで心臓治療了承 高難度の再生医療へ一歩. 日本経済新聞 電子版. 16 May 2018. ja. 2019-11-08.
  94. Web site: ｉＰＳ細胞の心筋シート移植、臨床研究を国が大筋了承：朝日新聞デジタル. 朝日新聞デジタル. 16 May 2018. ja. 2019-11-08.
  95. Wei H, Wang C, Guo R, Takahashi K, Naruse K . Development of a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells . Biochemical and Biophysical Research Communications . 520 . 3 . 600–605 . December 2019 . 31623826 . 10.1016/j.bbrc.2019.09.119 . free .
  96. Web site: First transfusions of "manufactured" blood planned for 2016 . 23 April 2014 . Gizmag.com . 2014-04-23.
  97. Garber K . RIKEN suspends first clinical trial involving induced pluripotent stem cells . Nature Biotechnology . 33 . 9 . 890–1 . September 2015 . 26348942 . 10.1038/nbt0915-890 . 205271169 .
  98. Tobita M, Konomi K, Torashima Y, Kimura K, Taoka M, Kaminota M . Japan's challenges of translational regenerative medicine: Act on the safety of regenerative medicine . Regenerative Therapy . 4 . 78–81 . June 2016 . 31245489 . 6581824 . 10.1016/j.reth.2016.04.001 . free .
  99. Web site: Information on p=roposed pilot study of the safety and feasibility of transplantation of autologous hiPSC-derived retinal pigment epithelium (RPE) cell sheets in patients with neovascular age-related macular degeneration. Riken Center for Developmental Biology. 23 July 2013. https://web.archive.org/web/20130626010639/http://www.cdb.riken.jp/en/02_research/0208_regenerative01.html. 26 June 2013. Research.
  100. News: Pioneering adult stem cell trial approved by Japan. Gallagher J . BBC News. 19 July 2013. 23 July 2013.
  101. News: First donor iPSC-derived RPE cell transplantation in AMD patient. 6 September 2017. RIKEN Center for Developmental Biology. 4 April 2017.
  102. News: First serious adverse reaction to iPS-derived retinal cell transplant reported. The Japan Times Online. 2018-01-17.
  103. Deinsberger J, Reisinger D, Weber B . Global trends in clinical trials involving pluripotent stem cells: a systematic multi-database analysis . npj Regenerative Medicine . 5 . 1 . 15 . 2020-09-11 . 32983575 . 7486930 . 10.1038/s41536-020-00100-4 . free .
  104. Web site: Knoepfler P . 2021-01-25. What are induced pluripotent stem cells or IPS cells & clinical prospects?. 2021-02-07. The Niche. en-US.
  105. Koga K, Wang B, Kaneko S . Current status and future perspectives of HLA-edited induced pluripotent stem cells . Inflammation and Regeneration . 40 . 23 . 2020 . 33014207 . 7528263 . 10.1186/s41232-020-00132-9 . free .
  106. Web site: Haridy R . Anti-Aging Stem Cell Treatment Proves Successful in Early Human Trials . New Atlas . 23 October 2017 .
  107. Sarkar TJ, Quarta M, Mukherjee S, Colville A, Paine P, Doan L, Tran CM, Chu CR, Horvath S, Qi LS, Bhutani N, Rando TA, Sebastiano V . 6 . Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells . Nature Communications . 11 . 1 . 1545 . March 2020 . 32210226 . 7093390 . 10.1038/s41467-020-15174-3 . 2020NatCo..11.1545S .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Induced pluripotent stem cell".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.