New lung organoid model allows the identification of primary cell‐intrinsic and secondary causes of congenital diaphragmatic hernia lung hypoplasia
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Summaries of the most recent articles published in STEM CELLS and STEM CELLS Translational Medicine.
Alpha‐1 antitrypsin (AAT)‐overexpressing MSCs display improved intrinsic properties and sustained efficacy in the prevention of type 1 diabetes onset
A new article describes a rapid screening technology for drug discovery and repurposing in the context of SARS‐CoV‐2/COVID-19
Due to their potential to treat degenerative diseases, many have hailed induced pluripotent stem cell‐based therapies as the future of regenerative medicine
A new study reports on the requirement of distinct signaling pathways for the ligament‐fibroblastic and cementoblastic differentiation of human PDLSCs.
High throughput single‐cell RNA‐seq technology deciphers the temporal‐ and cell type‐ specificity of long non‐coding RNA expression in the mammary gland epithelium
A new study describes a drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes and a multiwell optical mapping system
Newly described hypoimmunogenic human pluripotent stem cells could serve as invaluable cell sources for regenerative purposes.
Mesenchymal stem cell (MSC) therapy represents an exciting new means to treat autoimmune and inflammatory diseases; however, most human studies using MSCs alone have failed to achieve the sustained suppression of the autoimmune response. Researchers led by Charlie Strange and Hongjun Wang (Medical University of South Carolina, Charleston, South Carolina, USA) have now generated alpha‐1 antitrypsin (AAT)‐overexpressing MSCs that displayed improved intrinsic properties and sustained efficacy in the prevention of type 1 diabetes onset, an autoimmune disease. For all the details of this exciting new study, see STEM CELLS Translational Medicine.
A new STEM CELLS Translational Medicine article from Sally Esmail and Wayne R. Danter (123Genetix, London, Ontario, Canada) describes a rapid screening technology for drug discovery and repurposing in the context of SARS‐CoV‐2/COVID-19. The DeepNEU induced pluripotent stem-cell-based platform can create and validate computer simulations of artificial lung cells infected with SARS‐CoV‐2 to enable the rapid identification of antiviral therapeutic targets and drug repurposing and allow us to prepare for pandemic situations.
Due to their potential to treat degenerative diseases, many have hailed induced pluripotent stem cell (iPSC)‐based therapies as the future of regenerative medicine. The possibility of an autologous transplant that engraftments well in the long‐term represents a key promise of iPSC‐based therapies; however, the clinical translation of autologous iPSC‐based therapies has been slow due to the lack of a pre‐defined regulatory pathway. Now, researchers led by Kapil Bharti (National Eye Institute, National Institutes of Health, Bethesda, MA, USA) outline regulatory considerations for the development of autologous iPSC‐based products and discuss the challenges associated with the clinical manufacturing of autologous iPSCs and their derivatives. For all the details, see STEM CELLS Translational Medicine now!
Human periodontal ligament stem cells (hPDLSCs) differentiate into cementoblasts or ligaments progenitors, which can form tissues that hold tooth muscles to the pubic bone. A new study from the lab of Young‐Joo Jang (Dankook University, Cheonan, South Korea) aimed to decipher the mechanisms controlling hPDLSC differentiation. Lim et al. now report in STEM CELLS on the requirement for β‐catenin and TGF‐β1 activation for ligament‐fibroblastic differentiation and BMP7 and TGF‐β1 inhibition for cementoblastic differentiation.
In a recent STEM CELLS study, researchers led by Baowei Jiao (Chinese Academy of Sciences, Kunming, Yunnan, China) used high throughput single‐cell RNA‐seq technology to understand the temporal‐ and cell type‐ specificity of long non‐coding RNA (lncRNA) expression in the mammary gland epithelium. Xu et al. report that lncRNA specificity demarcates sub‐populations within the mammary epithelium, and that lineage‐specific lncRNAs can regulate lineage commitment through the formation of a lncRNA‐DNA‐DNA triplex and thus control the stemness of mammary stem cells.
Cell type heterogeneity, specificity, and translatability to human physiology confound in vitro drug screening systems that aim to discover new treatments for atrial fibrillation. In a recent STEM CELLS Translational Medicine study, researchers led by Glen F. Tibbits (British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada) describe the development of a drug screening platform using human induced pluripotent stem cell‐derived atrial cardiomyocytes (hiPSC‐aCMs) and a multiwell optical mapping system. Gunawan et al. report how the high‐content optical mapping system provides a readout of membrane voltage and Ca2+ transients, which serve as critical biomarkers of cardiac function in vitro, and how the hiPSC‐aCMs generated by this protocol possess atrial‐specific molecular profiles, functional signatures, and pharmacological response. Overall, these findings provide evidence of the applicability of this platform to preclinical drug screening for atrial fibrillation therapies.
In a recent STEM CELLS article, researchers led by Lin Ma and Xiaoqing Zhang (Tongji University School of Medicine, Shanghai, China) describe the construction of hypoimmunogenic human pluripotent stem cells (hPSCs) by targeting the beta‐2 microglobulin (B2M) and human leukocyte antigen- (HLA-) G proteins. Shi et al. report that engineered hypoimmunogenic hPSCs protect against immunotoxicity mediated by CD8+ T cells and natural killer cells; furthermore, they safeguarded environments with low immunogenicity by lowering inflammatory cytokines secretion. Overall, hypoimmunogenic hPSCs could serve as invaluable cell sources for regenerative purposes.
A new STEM CELLS Translational Medicine review article from the lab of Laura E. Sidney (University of Nottingham, UK) focuses on the potential of engineered mesenchymal stem cell (MSC) therapies that can be topically applied to the ocular surface to treat inflammatory disorders that cannot be managed through steroids or other means. Beeken et al. highlight different considerations, including whether the source of MSC isolation may impact the efficacy and safety of the therapy, and assess the feasibility of topical stem cell application to the ocular surface through an analysis of potential scaffolds.
A new STEM CELLS Translational Medicine article from the lab of Mohsin Khan (Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA) now reports that cardiac tissue stem‐like cells (CTSCs) derived from neonatal and aged mouse hearts exhibit unique gene expression patterns. Kurian et al. established that neonatal CTSCs express metabolism-related genes that increase the functional properties of the cells; however, adverse changes in the expression of said genes associates with the decreased function that accompanies the aging process. Additionally, this fascinating new study reports a novel role for mitochondrial protein uncoupling protein 2 (UCP2) in mediating beneficial effects on neonatal CTSCs. Importantly, the loss of UCP2 with age or in neonatal CTSCs blocks beneficial effects of metabolism on cellular function.
Skin stem cells express a variety of G‐protein coupled receptors (GPCRs), which play central roles in physiological functions and pathological conditions such as cancer and inflammatory diseases. Understanding GPCR signaling may provide important insight into the maintenance of stem cell identity and the approaches stem cells utilize to respond and adapt to microenvironmental changes. Furthermore, since GPCRs are the direct or indirect target of more than one-third of therapeutic drugs, they constitute a gateway for the pharmacological modulation of stem cell activity. Now, in a new STEM CELLS review article, researchers led by Ramiro Iglesias‐Bartolome (National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA) discuss the impact of GPCRs and their signaling partners in skin keratinocyte biology, particularly in the regulation of the epidermal stem cell compartment.