Inhibition of Notch Signaling in Human Embryonic Stem Cell-Derived Neural Stem Cells Delays G1/S Phase Transition and Accelerates Neuronal Differentiation In Vitro and In Vivo

In 2011, Goldring and colleagues published a review article describing the potential safety issues of novel stem cell-derived treatments. Immunogenicity and immunotoxicity of the administered cell product were considered risks in the light of clinical experience of transplantation. The relative immunogenicity of mesenchymal stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) was being addressed through in vitro and in vivo models. But the question arose as to whether the implanted cells needed to be identical to the recipient in every respect, including epigenetically, to evade immune recognition? If so, this set a high bar which may preclude use of many cells derived from iPSCs which have vestiges of a fetal phenotype and epigenetic memory of their cell of origin. However, for autologous iPSCs, the immunogenicity reduces once the surface antigen expression profile becomes close to that of the parent somatic cells. Therefore, a cell product containing incompletely differentiated cells could be more immunogenic. The properties of the administered cells, the immune privilege of the administration site, and the host immune status influence graft success or failure. In addition, the various approaches available to characterize potential immunogenicity of a cell therapy will be discussed.

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Blockade of STAT3 Causes Severe In Vitro and In Vivo Maturation Defects in Intestinal Organoids Derived from Human Embryonic Stem Cells

Journal of Clinical Medicine ◽

10.3390/jcm8070976 ◽

2019 ◽

Vol 8 (7) ◽

pp. 976 ◽

Cited By ~ 2

Author(s):

Kwang Bo Jung ◽

Ohman Kwon ◽

Mi-Ok Lee ◽

Hana Lee ◽

Ye Seul Son ◽

...

Keyword(s):

Stem Cells ◽

Human Embryonic Stem Cell ◽

In Vitro Maturation ◽

Embryonic Stem ◽

Generating Functional ◽

Intestinal Maturation ◽

Intestinal Organoids ◽

Hesc Lines

Human intestinal organoids (hIOs), which resemble the human intestine structurally and physiologically, have emerged as a new modality for the study of the molecular and cellular biology of the intestine in vitro. We recently developed an in vitro maturation technique for generating functional hIOs from human pluripotent stem cells (hPSCs). Here, we investigated the function of STAT3 for inducing in vitro maturation of hIOs. This was accompanied by the tyrosine phosphorylation of STAT3, whereas treatment with pharmacological inhibitors of STAT3 suppressed the phosphorylation of STAT3 and the expression of intestinal maturation markers. We generated and characterized STAT3 knockout (KO) human embryonic stem cell (hESC) lines using CRISPR/Cas9-mediated gene editing. We found that STAT3 KO does not affect the differentiation of hESCs into hIOs but rather affects the in vitro maturation of hIOs. STAT3 KO hIOs displayed immature morphologies with decreased size and reduced budding in hIOs even after in vitro maturation. STAT3 KO hIOs showed markedly different profiles from hIOs matured in vitro and human small intestine. Additionally, STAT3 KO hIOs failed to maintain upon in vivo transplantation. This study reveals a core signaling pathway consisting of STAT3 controlling the in vitro maturation of hIOs derived from hPSCs.

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IRON OXIDE LABELING OF HUMAN EMBRYONIC STEM CELL-DERIVED CARDIOVASCULAR CELLS: A NOVEL METHOD OF TRACKING STEM CELLS IN VIVO

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(15)60849-x ◽

2015 ◽

Vol 65 (10) ◽

pp. A849

Author(s):

Shone Almeida ◽

Rhys Skelton ◽

Stanislas Rapacchi ◽

Peng Zhao ◽

Peng Hu ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Iron Oxide ◽

Embryonic Stem Cell ◽

Human Embryonic Stem Cell ◽

Embryonic Stem ◽

Novel Method ◽

Cardiovascular Cells

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Nanofiber Matrices Promote the Neuronal Differentiation of Human Embryonic Stem Cell-Derived Neural Precursors In Vitro

Tissue Engineering Part A ◽

10.1089/ten.tea.2010.0377 ◽

2011 ◽

Vol 17 (5-6) ◽

pp. 855-863 ◽

Cited By ~ 77

Author(s):

Vasiliki Mahairaki ◽

Shawn H. Lim ◽

Gregory T. Christopherson ◽

Leyan Xu ◽

Igor Nasonkin ◽

...

Keyword(s):

Stem Cell ◽

Embryonic Stem Cell ◽

Neuronal Differentiation ◽

Human Embryonic Stem Cell ◽

Embryonic Stem ◽

Neural Precursors

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Induction of Human Embryonic stem cell derived retinal stem cells in vitro using transient overexpression of messenger RNA for BLIMP, ONECUT1 and OTX2

10.33015/dominican.edu/2016.bio.11 ◽

2016 ◽

Author(s):

Helen Cifuentes

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Embryonic Stem Cell ◽

Messenger Rna ◽

Human Embryonic Stem Cell ◽

Embryonic Stem ◽

Transient Overexpression ◽

Retinal Stem Cells

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Biofunctionalised bacterial cellulose scaffold supports the patterning and expansion of human embryonic stem cell-derived dopaminergic progenitor cells

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02639-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Miranda Robbins ◽

Venkat Pisupati ◽

Roberta Azzarelli ◽

Samer I. Nehme ◽

Roger A. Barker ◽

...

Keyword(s):

Parkinson’S Disease ◽

Stem Cells ◽

Parkinson's Disease ◽

Stem Cell ◽

Embryonic Stem Cell ◽

Bacterial Cellulose ◽

Progenitor Cells ◽

Human Embryonic Stem Cell ◽

Embryonic Stem

Abstract Background Stem cell-based therapies for neurodegenerative diseases like Parkinson’s disease are a promising approach in regenerative medicine and are now moving towards early stage clinical trials. However, a number of challenges remain including the ability to grow stem cells in vitro on a 3-dimensional scaffold, as well as their loss, by leakage or cell death, post-implantation. These issues could, however, be helped through the use of scaffolds that support the growth and differentiation of stem cells both in vitro and in vivo. The present study focuses on the use of bacterial cellulose as an in vitro scaffold to promote the growth of different stem cell-derived cell types. Bacterial cellulose was used because of its remarkable properties such as its wettability, ability to retain water and low stiffness, all of which is similar to that found in brain tissue. Methods We cultured human embryonic stem cell-derived progenitor cells on bacterial cellulose with growth factors that were covalently functionalised to the surface via silanisation. Epifluorescence microscopy and immunofluorescence were used to detect the differentiation of stem cells into dopaminergic ventral midbrain progenitor cells. We then quantified the proportion of cells that differentiated into progenitor cells and compared the effect of growing cells on biofunctionalised cellulose versus standard cellulose. Results We show that the covalent functionalisation of bacterial cellulose sheets with bioactive peptides improves the growth and differentiation of human pluripotent stem cells into dopaminergic neuronal progenitors. Conclusions This study suggests that the biocompatible material, bacterial cellulose, has potential applications in cell therapy approaches as a means to repair damage to the central nervous system, such as in Parkinson’s disease but also in tissue engineering.

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In Vitro Generation of Oocyte Like Cells and Their In Vivo Efficacy: How Far We have been Succeeded

Cells ◽

10.3390/cells9030557 ◽

2020 ◽

Vol 9 (3) ◽

pp. 557 ◽

Cited By ~ 2

Author(s):

Dinesh Bharti ◽

Si-Jung Jang ◽

Sang-Yun Lee ◽

Sung-Lim Lee ◽

Gyu-Jin Rho

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Embryonic Stem ◽

In Vivo Studies ◽

Special Focus ◽

Morphological Alterations ◽

Cell Sources ◽

Induced Pluripotent

In the last few decades, stem cell therapy has grown as a boon for many pathological complications including female reproductive disorders. In this review, a brief description of available strategies that are related to stem cell-based in vitro oocyte-like cell (OLC) development are given. We have tried to cover all the aspects and latest updates of the in vitro OLC developmental methodologies, marker profiling, available disease models, and in vivo efficacies, with a special focus on mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs) usage. The differentiation abilities of both the ovarian and non-ovarian stem cell sources under various induction conditions have shown different effects on morphological alterations, proliferation- and size-associated developments, hormonal secretions under gonadotropic stimulations, and their neo-oogenesis or folliculogenesis abilities after in vivo transplantations. The attainment of characters like oocyte-like morphology, size expansion, and meiosis initiation have been found to be major obstacles during in vitro oogenesis. A number of reports have either lacked in vivo studies or have shown their functional incapability to produce viable and healthy offspring. Though researchers have gained many valuable insights regarding in vitro gametogenesis, still there are many things to do to make stem cell-derived OLCs fully functional.

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