Assessment of iPSC teratogenicity throughout directed differentiation toward an alveolar-like phenotype

Mitchell, A. B.; Wanczyk, Heather; Jensen, Todd; Finck, Christine

doi:10.1016/j.diff.2019.01.003

Cited by 19 publications

(15 citation statements)

References 18 publications

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“…Pluripotent stem cells derived from somatic cells or iPSCs not only bypass the ethical concerns of stem cell harvesting from the embryo but also avoids immune rejection by using an autologous cell source [56]. However, iatrogenic tumorigenesis from the persistence of iPSCs in the differentiated cell population remains a major problem for cell therapy using iPSCs [57,58]. The induction of iPSC differentiation entails complex differentiation steps with specific culture medium, growth factors, cytokines, and other supplements, transfection-guided differentiation may simplify and shorten this process [59,60].…”

Section: Discussionmentioning

confidence: 99%

Characterization and Optimization of Chitosan-Coated Polybutylcyanoacrylate Nanoparticles for the Transfection-Guided Neural Differentiation of Mouse Induced Pluripotent Stem Cells

Lin

Lai

Chang

et al. 2021

IJMS

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Gene transfection is a valuable tool for analyzing gene regulation and function, and providing an avenue for the genetic engineering of cells for therapeutic purposes. Though efficient, the potential concerns over viral vectors for gene transfection has led to research in non-viral alternatives. Cationic polyplexes such as those synthesized from chitosan offer distinct advantages such as enhanced polyplex stability, cellular uptake, endo-lysosomal escape, and release, but are limited by the poor solubility and viscosity of chitosan. In this study, the easily synthesized biocompatible and biodegradable polymeric polysorbate 80 polybutylcyanoacrylate nanoparticles (PS80 PBCA NP) are utilized as the backbone for surface modification with chitosan, in order to address the synthetic issues faced when using chitosan alone as a carrier. Plasmid DNA (pDNA) containing the brain-derived neurotrophic factor (BDNF) gene coupled to a hypoxia-responsive element and the cytomegalovirus promotor gene was selected as the genetic cargo for the in vitro transfection-guided neural-lineage specification of mouse induced pluripotent stem cells (iPSCs), which were assessed by immunofluorescence staining. The chitosan-coated PS80 PBCA NP/BDNF pDNA polyplex measured 163.8 ± 1.8 nm and zeta potential measured −34.8 ± 1.8 mV with 0.01% (w/v) high molecular weight chitosan (HMWC); the pDNA loading efficiency reached 90% at a nanoparticle to pDNA weight ratio of 15, which also corresponded to enhanced polyplex stability on the DNA stability assay. The HMWC-PS80 PBCA NP/BDNF pDNA polyplex was non-toxic to mouse iPSCs for up to 80 μg/mL (weight ratio = 40) and enhanced the expression of BDNF when compared with PS80 PBCA NP/BDNF pDNA polyplex. Evidence for neural-lineage specification of mouse iPSCs was observed by an increased expression of nestin, neurofilament heavy polypeptide, and beta III tubulin, and the effects appeared superior when transfection was performed with the chitosan-coated formulation. This study illustrates the versatility of the PS80 PBCA NP and that surface decoration with chitosan enabled this delivery platform to be used for the transfection-guided differentiation of mouse iPSCs.

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Section: Discussionmentioning

confidence: 99%

Characterization and Optimization of Chitosan-Coated Polybutylcyanoacrylate Nanoparticles for the Transfection-Guided Neural Differentiation of Mouse Induced Pluripotent Stem Cells

Lin

Lai

Chang

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Also, in organ transplantation with current limitations about lack of donors and its immunogenic problems, iPSCs can be offered as one of the best sources to make patient-specific organs with fewer problems after implantation [133]. Some pieces of evidence prove that the increased expression of decorin and lumican genes by iPSCs as they differentiate can begin to repress recruitment of endothelial cells in hosts [137]. However, differentiating iPSCs display the lack of pluripotency simultaneous with a concurrent rise in the expression of known tumor suppressors, particularly the ECM mentioned proteins [137].…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 99%

“…Some pieces of evidence prove that the increased expression of decorin and lumican genes by iPSCs as they differentiate can begin to repress recruitment of endothelial cells in hosts [137]. However, differentiating iPSCs display the lack of pluripotency simultaneous with a concurrent rise in the expression of known tumor suppressors, particularly the ECM mentioned proteins [137]. Therefore, the issue forms a main considerable subject in iPSC using for lung alveolar tissue regeneration.…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 99%

Stem Cell Therapy Potency in Personalizing Severe COVID-19 Treatment

Basiri

Mansouri

Azari

et al. 2021

Stem Cell Rev and Rep

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Currently, there are no specific and efficient vaccines or drugs for COVID-19, particularly in severe cases. A wide range of variations in the clinical symptoms of different patients attributed to genomic differences. Therefore, personalized treatments seem to play a critical role in improving these symptoms and even similar conditions. Prompted by the uncertainties in the area of COVID-19 therapies, we reviewed the published papers and concepts to gather and provide useful information to clinicians and researchers interested in personalized medicine and cell-based therapy. One novel aspect of this study focuses on the potential application of personalized medicine in treating severe cases of COVID-19. However, it is theoretical, as any real-world examples of the use of genuinely personalized medicine have not existed yet. Nevertheless, we know that stem cells, especially MSCs, have immune-modulatory effects and can be stored for future personalized medicine applications. This theory has been conjugated with some evidence that we review in the present study. Besides, we discuss the importance of personalized medicine and its possible aspects in COVID-19 treatment, then review the cell-based therapy studies for COVID-19 with a particular focus on stem cell-based therapies as a primary personalized tool medicine. However, the idea of cell-based therapy has not been accepted by several scientific communities due to some concerns of lack of satisfactory clinical studies; still, the MSCs and their clinical outcomes have been revealed the safety and potency of this therapeutic approach in several diseases, especially in the immune-mediated inflammatory diseases and some incurable diseases. Promising outcomes have resulted in that clinical studies are going to continue.

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“…This currently limits the utility of these cells in clinical studies. Furthermore, recent studies indicate that dissemination of cells or pre-differentiation of iPSCs in lung progenitor cells might overcome this problem (278,279). However, this must be confirmed prior to the first clinical implementation.…”

Section: Stem Cells and Vascular Regeneration In Copd/emphysemamentioning

confidence: 99%

Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target

Karnati

Seimetz

Kleefeldt

et al. 2021

Front. Cardiovasc. Med.

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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and encompasses chronic bronchitis and emphysema. It has been shown that vascular wall remodeling and pulmonary hypertension (PH) can occur not only in patients with COPD but also in smokers with normal lung function, suggesting a causal role for vascular alterations in the development of emphysema. Mechanistically, abnormalities in the vasculature, such as inflammation, endothelial dysfunction, imbalances in cellular apoptosis/proliferation, and increased oxidative/nitrosative stress promote development of PH, cor pulmonale, and most probably pulmonary emphysema. Hypoxemia in the pulmonary chamber modulates the activation of key transcription factors and signaling cascades, which propagates inflammation and infiltration of neutrophils, resulting in vascular remodeling. Endothelial progenitor cells have angiogenesis capabilities, resulting in transdifferentiation of the smooth muscle cells via aberrant activation of several cytokines, growth factors, and chemokines. The vascular endothelium influences the balance between vaso-constriction and -dilation in the heart. Targeting key players affecting the vasculature might help in the development of new treatment strategies for both PH and COPD. The present review aims to summarize current knowledge about vascular alterations and production of reactive oxygen species in COPD. The present review emphasizes on the importance of the vasculature for the usually parenchyma-focused view of the pathobiology of COPD.

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Assessment of iPSC teratogenicity throughout directed differentiation toward an alveolar-like phenotype

Cited by 19 publications

References 18 publications

Characterization and Optimization of Chitosan-Coated Polybutylcyanoacrylate Nanoparticles for the Transfection-Guided Neural Differentiation of Mouse Induced Pluripotent Stem Cells

Characterization and Optimization of Chitosan-Coated Polybutylcyanoacrylate Nanoparticles for the Transfection-Guided Neural Differentiation of Mouse Induced Pluripotent Stem Cells

Stem Cell Therapy Potency in Personalizing Severe COVID-19 Treatment

Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target

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