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Pluripotent Stem Cells

Hip Replacement Surgery Byproduct Yields Autologous Stem Cell

Taking advantage of hip replacement therapy, researchers have isolated periosteal stem cell populations and shown their potential usefulness for chondrogenic differentiation.

Stem Cell Defects Uncovered in DS

Down's syndrome (DS) is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21 and is the most common chromosome abnormality in humans, associated with physical growth delays and a severe degree of intellectual disability. It is also associated with early aging and related disorders and, as recent research has linked aging to impaired or exhausted stem cells (Liu and Rando), suggests that DS may also be associated with adult stem cell defects. In a recent report in ­Nature, researchers from the laboratory of Michael F. Clarke at Stanford University School of Medicine, California, USA have begun to unravel the molecular underpinnings of DS through the examination of one of the genes known to be triplicated in human DS: the deubiquitinase Usp16 gene.

Immune Response to iPSC-Derivatives Analysed in Non-human Primates

Recent studies on the host immune response to induced pluripotent stem cells (iPSCs) in mice found that while iPSC-derived teratomas raised a potentially deleterious immune response in genetically identical mice (Zhao et al), their derivatives seem to lack this effect (Araki et al and Guha et al). To better simulate a clinical situation, in a recent study in Stem Cell Reports the group of Jun Takahashi at Kyoto University, Japan have compared immunological responses of dopaminergic (DA) neurons (the cells required for cell replacement therapy in Parkinson's Disease) derived from cynomolgus monkeys in an autologous and allogeneic manner (Morizane et al).

Cell Cycle and Stem Cells: An intimate Relationship Delineated

The importance of the cell cycle to human embryonic stem cells (hESCs) is demonstrated by a wealth of data emanating from multiple labs across the world.

Oct4 - Pluripotent but Not Totipotent

Alongside Nanog, Oct4 is one of the quintessential pluripotency associated transcription factors; considered to be the genetic 'master switch' in the establishment of totipotency to pluripotency during the life cycle of mammals (Pesce et al) and presumed to be the most upstream gene in the molecular circuitry of pluripotency (Jaenisch and Young).  However, in a study published in Nature Cell Biology, researchers from the laboratory of Hans R. Schöler at the Max Planck Institute for Molecular Biomedicine, Münster, Germany have now provided strong proof that this may not be true (Wu et al); they find that while Oct4 is required for pluripotency, it is not required for totipotency.

Pluripotent Stem Cell Derived "Minibrains" to Aid Research

Original article from Nature

Pluripotent Stem Cell Derived "Minibrains" to Aid Research

The generation of cerebral organoids (or "mini-brains") from pluripotent stem cell sources is one of the most exciting and widely reported recent research articles.   This study from the laboratory of Juergen A. Knoblich at the Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna , Austria could have huge importance in the study of human brain development and the study of related diseases (Lancaster et al).   Herein, we briefly describe the details behind the headline.


iPSC Perfection?

iPSC Perfection?

Since the birth of the field of induced pluripotent stem cells (iPSCs), each passing month has brought forth numerous papers reporting new tweaks to further improve the reprogramming process; a new chemical here, a replacement transcription factor there, each time removing one small barrier, making reprogramming more rapid or uncovering a new piece of the machinery that controls it. Now, in what amounts to a quantum leap forward, the groups of Jacob Hanna and Noa Novershtern at the Weizmann Institute of Science, Rehevot, Israel have reported that the removal of a distinct epigenetic repressor element; Mbd3, can boost the reprogramming process to 100% and allows the transition to pluripotency on a remarkably fast, synchronized schedule (Rais, Zviran & Geula et al).


Improved Differentiation Strategy for Parkinson’s Therapy

"Improved Cell Therapy Protocols for Parkinson's Disease Based on Differentiation Efficiency and Safety of hESC-, hiPSC-, and Non-Human Primate iPSC-Derived Dopaminergic Neurons"

From Stem Cells

The replacement of dopaminergic (DA) neurons in the ventral midbrain (VM) is seen as a viable and beneficial treatment in Parkinson's disease (PD), but is however hampered by the poor dopaminergic differentiation capacity of pluripotent cells; the optimal sources for the derivation of these specialized neurons (Kirkeby et al, Kriks et al and Xi et al).   Sundberg et alfrom the laboratory of Ole Isacson at the Neuroregeneration Laboratories, Harvard Medical School/McLean Hospital, USA now report on their optimisation of the signaling parameters for VM DA neuron specification from pluripotent stem cells sources through the application of knowledge gleaned from developmental studies (Cooper et al, Hynes et al, Prakash et al, and Ye et al).

Effective Mutant Gene Knockdown in Disease Specific iPSCs

“Rapid Generation of Functional Dopaminergic Neurons From Human Induced Pluripotent Stem Cells Through a Single-Step Procedure Using Cell Lineage Transcription Factors”

From Stem Cells Translational Medicine

A study recently published in Stem Cells TM from the group of Tobias Cantz at the Hannover Medical School, Germany has united two exciting technologies; the use of third generation lentiviral vectors (LVs), recently shown to have amazing potency in ex vivo gene therapy, and that of the ever evolving field of patient specific induced pluripotent stem cells (iPSCs).   Excitingly, they have demonstrated the efficacy of LVs in gene silencing using the expression of a short hairpin RNA (shRNA) directed against mutant mRNA in a disease specific iPSC line (Eggenschwiler et al).

In vivo reprogramming in living mice

A recent paper in Nature from Spanish scientists at the Spanish National Cancer Research Center (CNIO) reports the reprogramming of cells to generate induced pluripotent stem cells (iPSCs) in adult micein vivo. This work, led by Manuel Serrano who heads the Tumour suppression Group at CNIO, advances the current knowledge of iPSCs by showing that there may be no need to remove somatic tissues from an organism for reprogramming to occur inside a petri dish in a laboratory incubator, but that reprogramming can be achieved inside a living organism. The authors performed their work in reprogrammable mice, turning on the 4 classic Yamanaka pluripotency factors (Oct4, Klf4, Sox2 and c-Myc/OKSM) via a lentiviral dox-inducible system. In their paper, Abad et al. describe that inducing too much expression of OKSM was catastrophic, causing fatal teratoma formation, however by determining the right dosage they were able to achieve teratoma formation in situ in multiple organs in live mice that could be studied.   Across multiple organs the authors also found in situ dedifferentiated somatic cells which lost the expression of mature markers and gained expression of the pluripotency marker NANOG.   Termed ‘in vivo iPSCs’, these were found in highest frequency in abdominal organs, but were also found circulating within the bloodstream, and were easily obtainable from the blood of induced mice.   Intriguingly, in vivo iPSCs were more similar to embryonic stem cells (ECSs) than in vitro-generated iPSCs, with in vivo iPSCs demonstrating totipotency by forming extra-somatic cell types, indicating greater plasticity than ESCs which are pluripotent in nature.  


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