Kidney dysplasia has been associated with the failure of kidney progenitor cells during development, and, recently, progress has been made in understanding the importance of epigenetic mechanisms to this phenomenon.
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Summaries of the most recent articles published in STEM CELLS and STEM CELLS Translational Medicine.
Culturing cells from prostate cancer biopsies to study mechanisms of disease and discover novel treatments suffers from many difficulties; however, a new study from the laboratory of Rakesh Heer
Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disease, leads to kidney failure in most patients. While mutations in the Polycystin 1 (PKD1) gene cause 85% of cases, we do not fully understand how dysregulation of PKD1 leads to cyst formation on a molecular level.
The four transcription factors that make up the Yamanaka “cocktail” (Oct4, Sox2, Klf4, and Myc, or OSKM) are well known for their capacity to reprogram somatic cells into induced pluripotent stem cells (iPSCs).
A recent STEM CELLS Translational Medicine article from the labs of
Culturing cells from prostate cancer biopsies to study mechanisms of disease and discover novel treatments suffers from many difficulties; however, a new study from the laboratory of Rakesh Heer (Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK) has established a new means to grow “mini 3D prostates” in the laboratory. Hepburn et al. provide proof of concept for genetic modifications in this innovative model, which lays the foundations for new preclinical approaches to personalized care that were previously considered a challenging prospect. The team hopes next to develop genetically engineered prostate cancers in a dish that are tailored to the specific genetic profiles of individual patients and determine their responses to a range of drug treatments. For all the exciting details, see STEM CELLS Translational Medicine now!
Researchers from the lab of Ton J. Rabelink (Leiden University Medical Center, Leiden, The Netherlands) recently sought to explore the maturity of endothelial cells derived from human induced pluripotent stem cells (hiPSC-ECs) by investigating their ability to express von Willebrand factor (VWF) and formation of Weibel‐Palade bodies (WPBs). Overall, Tiemeier et al. found that metabolic immaturity hampered proper hiPSC-EC function, and the formation of VWF and WPBs required the lowering of the intracellular pH of hiPSC-ECs. For more information on this fascinating new study, head over to STEM CELLS Translational Medicine.
Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disease, leads to kidney failure in most patients. While mutations in the Polycystin 1 (PKD1) gene cause 85% of cases, we do not fully understand how dysregulation of PKD1 leads to cyst formation on a molecular level. Now, a new STEM CELLS Translational Medicine study from Joost H. Gribnau (Erasmus Medical Center Rotterdam, Netherlands) reports on the generation of induced pluripotent stem cells (iPSCs) from ADPKD patients to study the function of PKD1 in kidney development and cyst formation in vitro. Kenter et al. report that the iPSCs display the germline and autosomal mutations implicated in ADPKD and an epigenetic memory of kidney epithelial cells and therefore represent a powerful model to study ADPKD in vitro.
The four transcription factors that make up the Yamanaka “cocktail” (Oct4, Sox2, Klf4, and Myc, or OSKM) are well known for their capacity to reprogram somatic cells into induced pluripotent stem cells (iPSCs). Now, Huafeng Xie and Thomas Graf discuss a recent paper from Wang et al. in Nature Communications that describes the unexpected discovery that short‐term activation of OSKM expression in acute myeloid leukemia cells in vivo induces apoptosis while negligibly affecting normal hematopoietic stem and progenitor cells. Head over to STEM CELLS to discover the potential implications of these findings for novel anti‐cancer strategies.
A recent STEM CELLS Translational Medicine article from the labs of Aijun Wang and Ping Zhou (University of California Davis, Sacramento, CA, USA) demonstrated that induced pluripotent stem cells (iPSCs) derived from hemophilia A patients can provide an ample supply of endothelial cells that can be genetically modified to produce functional factor VIII. Rose et al. describe how the stable engraftment of endothelial cells in neonatal and adult animals and the functional correction or alleviation of hemophilia A by these endothelial cells in animal models provide the basis for potential therapeutic development of corrected‐iPSC‐derived endothelial cells for the treatment of hemophilia A.
The impact of extracellular matrix mechanical cues and mechanotransduction signaling on inner ear progenitor cell (IEPCs) fate remains relatively undescribed; however, researchers led by Wenyan Li and Huawei Li (Fudan University, Shanghai, China) now provide the first demonstration that Ras homolog family member A (RhoA)‐mediated actin cytoskeletal contractility plays a critical role in regulating the response of IEPCs to microenvironmental mechanical cues through their application of suspension and encapsulated culture systems. More specifically, this new STEM CELLS article from Xia et al. characterized Yes-associated protein 1 (YAP1) as a mediator of mechanotransduction signaling in the expansion of IEPCs, partly through regulating b-catenin activity.
A recent STEM CELLS study from the laboratories of Pratibha Singh and Louis M. Pelus (Indiana University School of Medicine, Indianapolis, IN, USA) recently identified how the bone marrow niche intrinsic CXCR4‐SDF‐1 axis supports hematopoietic stem and progenitor cell (HSPC) maintenance and retention under steady‐state conditions and also promotes early hematopoietic recovery after myeloablation. The team´s findings suggest that targeted modulation of CXCR4 signaling in the bone marrow niche may alleviate irradiation/chemotherapy‐induced bone marrow stromal damage and enhance blood cell production in patients undergoing stem cell transplantation for several hematological complications including leukemia, lymphoma, and aplastic anemia, as well as metabolic disorders such as diabetes.
Mesenchymal stem cells (MSCs) represent a popular platform for regenerative medicine due to their ability to home to damaged organs and secrete molecules that promote cell growth and suppress inflammation; however, there remains a need to optimize their therapeutic effect for clinical translation. A team of researchers led by Avnesh S. Thakor (Stanford University, Palo Alto, CA, USA) now reviews current knowledge regarding how ultrasound can enhance the ability of MSCs to secrete regenerative molecules or make target organs a more attractive destination for infused MSCs. See STEM CELLS Translational Medicine for the biological effects and preclinical applications of ultrasound to MSC‐based therapies.
Due to the increasing awareness in the cell therapy community of a need to better understand the biology of transplanted cells in the myocardium, researchers led by Martin Rodriguez‐Porcel (Mayo Clinic, Rochester, Minnesota, USA) previously reported the use of reporter gene labeling of stem cells to track cell viability kinetics. Peterson et al. extend these studies and report the development and validation of a pathway‐specific reporter gene to study the changing phenotype of mesenchymal stem cells (MSCs) after transplantation into the ischemic myocardium. In their new STEM CELLS reports, the team also proposes an algorithm for the development of these monitoring strategies for the entire scientific community to adopt.
Making high‐quality dopamine‐producing cells for basic studies or small molecule screening remains critical to the development of novel therapeutics for ventral midbrain disorders. However, many ventral midbrain assays suffer from low signal to noise ratio thanks to low levels of dopamine and tyrosine hydroxylase, the rate‐limiting enzyme for dopamine synthesis. In their new STEM CELLS Translational Medicine study, researchers led by Carl Ernst (McGill University, Montreal, Quebec, Canada) now demonstrate that an L‐type calcium agonist can significantly increase tyrosine hydroxylase protein levels as well as dopamine content and release from ventral midbrain cells derived from human skin. Jefri et al. hope that this advance will improve the accuracy of disease modeling and small molecule screening for disorders of the ventral midbrain, including Parkinson's disease.