Current Reprogramming Systems in Regenerative Medicine: From Somatic Cells to Induced Pluripotent Stem Cells

Hu, Chenxia

doi:10.2217/rme.15.79

Cited by 14 publications

(4 citation statements)

References 141 publications

(141 reference statements)

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“…The transient expression of OSKM proteins primes enhancer regions for pluripotency associated genes, while cMyc associates with gene promoters to help activate endogenous expression of OCT4, SOX2, KLF4, and NANOG, thereby establishing long term pluripotency [24][25][26][27][28]. Several studies have shown that the method of introducing OSKM transgenes may slightly affect the efficiency of reprogramming without altering iPSC cell physiology, pluripotency, differentiation potential, or gene expression [29][30][31][32][33][34]. The activation of additional factors such as LIN28 and NANOG has been shown to greatly enhance reprogramming efficiency [34].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming

et al. 2018

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Epigenetic enzymes regulate higher-order chromatin architecture and cell-type specific gene expression. The ATPase BRG1 and the SWI/SNF chromatin remodeling complex are epigenetic enzymes that regulate chromatin accessibility during steady and transitional cell states. Experiments in mice show that the loss of BRG1 inhibits cellular reprogramming, while studies using human cells demonstrate that the overexpression of BRG1 enhances reprogramming. We hypothesized that the variation of SWI/SNF subunit expression in the human population would contribute to variability in the efficiency of induced pluripotent stem cells (iPSC) reprogramming. To examine the impact of an individual's sex, ancestry, and age on iPSC reprogramming, we created a novel sex and ancestry balanced cohort of 240 iPSC lines derived from human dermal fibroblasts (DF) from 80 heathy donors. We methodically assessed the reprogramming efficiency of each DF line and then quantified the individual and demographic-specific variations in SWI/SNF chromatin remodeling proteins and mRNA expression. We identified BRG1, BAF155, and BAF60a expression as strongly correlating with iPSC reprogramming efficiency. Additionally, we discovered that high efficiency iPSC reprograming is negatively correlated with donor age, positively correlated with African American descent, and uncorrelated with donor sex. These results show the variations in chromatin remodeling protein expression have a strong impact on iPSC reprogramming. Additionally, our cohort is unique in its large size, diversity, and focus on healthy donors. Consequently, this cohort can be a vital tool for researchers seeking to validate observational results from human population studies and perform detailed mechanistic studies in a controlled cell culture environment. Stem Cells 2018;36:1697-1708.

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Section: Introductionmentioning

confidence: 99%

Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming

et al. 2018

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“…These emerging technologies motivate new research trends with many exciting achievements, but low reprogramming efficiency and genomic modification steps still Fig. 3 Animal breeding with DSC: cloned animals are bred by DSC (his one XY); female animals inherit the X chromosome from the female animal that parented her parent; breeding new hybrids by DSC restrict the clinical use of these cells [151]. For example, iPSCs always possess somatic-coding mutations [127].…”

Section: Resultsmentioning

confidence: 99%

“…In addition, accumulating preclinical data also support the safety and efficacy of iPSCs [ 150 ]. These emerging technologies motivate new research trends with many exciting achievements, but low reprogramming efficiency and genomic modification steps still restrict the clinical use of these cells [ 151 ]. For example, iPSCs always possess somatic-coding mutations [ 127 ].…”

Section: Discussionmentioning

confidence: 99%

Double sperm cloning (DSC) is a promising strategy in mammalian genetic engineering and stem cell research

Zhang

Huang

et al. 2020

Stem Cell Res Ther

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Embryonic stem cells (ESCs) derived from somatic cell nuclear transfer (SCNT) and induced pluripotent stem cells (iPSCs) are promising tools for meeting the personalized requirements of regenerative medicine. However, some obstacles need to be overcome before clinical trials can be undertaken. First, donor cells vary, and the reprogramming procedures are diverse, so standardization is a great obstacle regarding SCNT and iPSCs. Second, somatic cells derived from a patient may carry mitochondrial DNA mutations and exhibit telomere instability with aging or disease, and SCNT-ESCs and iPSCs retain the epigenetic memory or epigenetic modification errors. Third, reprogramming efficiency has remained low. Therefore, in addition to improving their success rate, other alternatives for producing ESCs should be explored. Producing androgenetic diploid embryos could be an outstanding strategy; androgenic diploid embryos are produced through double sperm cloning (DSC), in which two capacitated sperms (XY or XX, sorted by flow cytometer) are injected into a denucleated oocyte by intracytoplasmic sperm injection (ICSI) to reconstruct embryo and derive DSC-ESCs. This process could avoid some potential issues, such as mitochondrial interference, telomere shortening, and somatic epigenetic memory, all of which accompany somatic donor cells. Oocytes are naturally activated by sperm, which is unlike the artificial activation that occurs in SCNT. The procedure is simple and practical and can be easily standardized. In addition, DSC-ESCs can overcome ethical concerns and resolve immunological response matching with sperm providers. Certainly, some challenges must be faced regarding imprinted genes, epigenetics, X chromosome inactivation, and dosage compensation. In mice, DSC-ESCs have been produced and have shown excellent differentiation ability. Therefore, the many advantages of DSC make the study of this process worthwhile for regenerative medicine and animal breeding.

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“…The aim is to restore tissue function to normal. This aim could be achieved by stimulating the body's own repair mechanisms and/or creating organs and tissues in vitro and implanting them if the body is unable to [16]. However, there are many unknown mechanisms that act on stem cells within an organ or system.…”

Section: Application Of Differentiation Potency Of Epithelial Cells Imentioning

confidence: 99%

Stemness specificity of epithelial cells – application of cell and tissue technology in regenerative medicine

Rojewska

Popis

Jankowski

et al. 2018

Medical Journal of Cell Biology

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Stem cells are cells that have the potential to replicate and/or differentiate, becoming any tissue. This process could be theoretically repeated indefinitely and can be used to create or fix damaged parts any organ. There are many in vivo factors that cause stem cells to replicate and differentiate. Many of these interactions and mechanisms are still unknown. In vitro models have been successful in inducing stem cells to differentiate into the desired lineage using controlled methods. Recently, epithelial tissue has been successfully created using scaffolds on which stem cells are grown in vitro and then transplanted into the host. This transition creates significant problems. This is because in vitro -grown stem cells or stem cell-derived tissues are created in an isolated environment where virtually every aspect can be monitored and controlled. In vivo monitoring and controlling is significantly more difficult for a plethora of reasons. Cells in the body are constantly exposed to many signals and molecules which affect them. Many of the mechanisms behind these interactions and reactions are known but many others are not. As the corpus of knowledge grows, stem cells become closer to being applied in a clinical setting. In this paper, we review the current evidence on stem cell therapy in regenerative medicine and some of the challenges this field faces.

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Current Reprogramming Systems in Regenerative Medicine: From Somatic Cells to Induced Pluripotent Stem Cells

Cited by 14 publications

References 141 publications

Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming

Epigenetic Enzymes, Age, and Ancestry Regulate the Efficiency of Human iPSC Reprogramming

Double sperm cloning (DSC) is a promising strategy in mammalian genetic engineering and stem cell research

Stemness specificity of epithelial cells – application of cell and tissue technology in regenerative medicine

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