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Highlights of current exciting developments, ranging from research papers to court decisions to industry regulations

November 18, 2018

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

Past Buzz

November 15,2018 What’s the Stem Cells Buzz this Week? - Reciprocal Reprogramming, Synthetic mRNAs, hESC-derived Retinal Pigment Epithelium, and Combination Cell Therapy for Cirrhosis!

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

 

Reciprocal Reprogramming of Cancer Cells and Associated Mesenchymal Stem Cells 

The assessment of interactions between cancer stem cells (CSCs) and the stromal niche may improve our knowledge regarding the initiation and development of tumorigenesis. Now, researchers from the laboratory of Maty Tzukerman (Technion‐Israel Institute of Technology, Haifa, Israel) have provided evidence that human gastric cancer cells subvert gene expression and cytokine production in naïve mesenchymal stem cells to promote tumor progression through the maintenance of CSCs. Discover all the reciprocal reprogramming details at STEM CELLS now!

 

Synthetic mRNAs Drive Induced Pluripotent Stem Cell Differentiation 

As a means to avoid the application of genome‐integrating viruses, researchers from the labs of Mingyao Ying (Kennedy Krieger, Baltimore, Maryland, USA) and Jianmin Zhang (Peking Union Medical College, Beijing, China) investigated a new means to cells relevant for the treatment of neurological disorders. Xue et al. reported on the application of synthetic mRNAs coding proneural TFs to drive the rapid differentiation of induced pluripotent stem cells (iPSCs) into midbrain dopaminergic neurons. See STEM CELLS Translational Medicine now to read more on a study that may facilitate Parkinson's disease modeling and therapy, and guide the development of robust methods for generating various lineage‐specific progenies from iPSCs.

 

Voltage-Gated Ca2+ Channels in Human Embryonic Stem Cell-derived Retinal Pigment Epithelium 

The therapeutic efficacy of human embryonic stem cell (hESC)-derived cells relies on their proper functionality. For this reason, researchers from the lab of Soile Nymark (Tampere University of Technology, Tampere, Finland) set out to analyze the all-important voltage‐gated Ca2+ channels in hESC-derived retinal pigment epithelium (RPE). Using Whole‐cell patch‐clamp recordings, Korkka et al. discovered that hESC-derived RPE and native RPE displayed similar levels of functional voltage‐gated Ca2+ channels, which helped to control vascular endothelial growth factor secretion as well as in the phagocytosis of photoreceptor outer segments. For all the details, see STEM CELLS Translational Medicine for more!

 

A Novel Stem Cell-Macrophage Combination Therapy for Cirrhosis

The development of novel therapeutic approaches for liver fibrosis regression and regeneration represent possible means to treat patients suffering from cirrhosis, a life‐threatening condition. To this end, researchers from the labs of Atsunori Tsuchiya and Shuji Terai (Niigata University, Chuo‐ku, Niigata, Japan) recently reported on a new cell-based combination therapy. In their recent study, the authors describe how bone marrow‐derived mesenchymal stem cells and colony‐stimulating factor‐1‐induced bone marrow‐derived macrophages work together to improve liver function and fibrosis by enhancing host endogenous regenerative responses. Will this study pave the way for new treatments for cirrhosis? Find the answer over at STEM CELLS Translational Medicine!

 

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!

November 11,2018 What’s the Stem Cells Buzz this Week? - Regulating Neural Patterning, Cardiac Mesodermal Progenitors, iPSC Chondrogenesis with SMAD4, and Late Endothelial Progenitor Cells!

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

GLIS3 Regulates Anterior-Posterior Patterning

While studies have established the importance of several morphogens in anterior-posterior (A‐P) neural patterning, the mechanisms that regulate said morphogens remains relatively unknown. Now, new research from the lab of Anton M. Jetten (National Institutes of Health, NC, USA) established an essential role for the Krüppel‐like zinc finger transcription factor GLI‐Similar 3 (GLIS3) in the direct differentiation of human embryonic stem cells (hESCs) into posterior neural progenitor cells (NPCs), rather than the default anterior pathway. In this STEM CELLS study, Jeon at al. also report the importance of GLIS3-mediated transcriptional activation of WNT genes, including the strong posteriorizing factor WNT3A, for A‐P specification.

SMAD4 and Human Cardiac Mesodermal Progenitors

In the hope of understanding the stage‐specific molecular mechanisms of human cardiomyocyte progenitor formation and subsequent differentiation, researchers from the lab of Kenneth R. Chien (Karolinska Institutet, Stockholm, Sweden) recently defined the role of SMAD4 at the earliest stages of human cardiogenesis via the generation of SMAD4 mutant human embryonic stem cells (hESC). In summary, Xu et al. defined the role of SMAD4 at the earliest stages of human cardiogenesis, and the team anticipate that their findings will encourage research into human stem cell models of development and disease, treatments for congenital heart defects, and TGF beta signaling pathways. See STEM CELLS now for all the details.

 

Genome Editing for Human Induced Pluripotent Stem Cell Chondrogenesis

As the low efficiency and variability of chondrogenesis in human induced pluripotent stem cells (hiPSCs) represent a significant hurdle to their clinical application, researchers from the labs of Farshid Guilak (Washington University, St. Louis, Missouri) and Charles A. Gersbach (Duke University, Durham, NC, USA) sought to construct an improved differentiation protocol. In STEM CELLS, Adkar et al. now report on a highly efficient chondrogenic differentiation protocol via stepwise specification through a mesodermal lineage and the application of a genome‐engineered COL2A1‐GFP knock‐in hiPSC line to identify a purified progenitor population with improved chondrogenic potential. The team hopes that the development of processes for rapid and repeatable chondrogenic induction of iPSCs will enable the identification of novel therapies for joint diseases such as osteoarthritis.

B7-H3 in Late Endothelial Progenitor Cells

The isolation of late endothelial progenitor cells (LEPCs), circulating blood cells that can promote vascular repair, may represent an important cell type for the treatment of numerous conditions. Recent research from the lab of Je‐Yoel Cho (Seoul National University, Korea) discovered elevated cell surface expression of CD276 (B7‐H3) of LEPCs and its requirement for proliferation and migration. However, Son et al. established that this type I transmembrane glycoprotein inhibited endothelial cell differentiation, suggesting that B7‐H3 functions to maintain the cells in the progenitor stage. Overall, this STEM CELLS study indicates that B7‐H3 can be employed to acquire and maintain LEPCs, while blocking B7‐H3 promotes angiogenetic differentiation.

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!

November 9,2018 What’s the Stem Cells Buzz this Week? - Enhancing iPSC-EC Function, Regulating SMC Differentiation, Improving Gene Editing in HSCs, and Promoting BM-MSC Osteogenesis!

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

Endothelial Cell‐specific Molecule 1 Enhances the Function of iPSC-derived Endothelial Cells

New research from the lab of Andriana Margariti (Queen's University Belfast, UK) recently sought to understand the transcriptional regulation of endothelial cells generated from patient-derived human induced pluripotent stem cells (hiPSCs) to aid the treatment of vascular disease. In their new report, Vilà‐González et al. establish the relative importance of Endothelial cell‐specific molecule 1 (ESM1) signaling in improving the function and neovascularization potential in endothelial cells generated from iPSCs in vitro and in vivo. Discover more of the details at STEM CELLS now.

Glycoprotein M6B Regulates Smooth Muscle Cell Differentiation

Smooth muscle cells (SMCs) play a vital role in vascular development and the pathogenic process of vascular remodeling, although the molecular mechanisms governing their differentiation remain poorly understood. Now, researchers led by Ling Tao and Shan Wang (Fourth Military Medical University, Xi'an, Shaanxi, China) have demonstrated that glycoprotein M6B (GPM6B) regulates SMC differentiation through the activation of TGF-β-Smad2/3 signaling via direct interactions with TβRI. Zhang et al. anticipate that GPM6B will represent a potentially attractive target for the regulation of SMC differentiation and cardio-vascular regenerative medicine. See STEM CELLS now to discover more.

Improving Gene Editing Outcomes in Human Hematopoietic Stem Cells

The wide-ranging clinical application of CRISPR/Cas9‐mediated gene edited human hematopoietic stem cells (HSCs) as a treatment of genetic blood diseases requires the development of the technology to increase the precision of genetic modification. A STEM CELLS study led by Donald B. Kohn (University of California Los Angeles, Los Angeles, California, USA) now reports that a modified version of Cas9 with reduced nuclease activity in G1 phase of cell cycle combined with a transient increase in the proportion of cells in homology-directed repair (HDR)‐preferred phases (S/G2) leads to increased precision. Furthermore, Lomova et al. demonstrate that edited HSCs display a significant improvement after xenotransplantation into immune‐deficient mice, thereby encouraging the application of CRISPR/Cas9-modified HSCs in the treatment of congenital diseases of the blood system.

LncRNA-OG Promotes Bone Marrow-derived Mesenchymal Stem Cell Osteogenesis

Previous studies from Huiyong Shen and Yanfeng Wu (Sun Yat‐sen University, Guangzhou, Guangdong, China) analyzed long noncoding RNA (lncRNA) expression profiles in during the osteogenesis of bone marrow‐derived mesenchymal stem cells (BM‐MSCs). Now, Tang et al. report in a STEM CELLS study that a novel positive functional osteogenesis-associated lncRNA, lncRNA-OG, regulates the activation of BMP signaling pathway by interacting with the major pre-mRNA-binding protein heterogeneous nuclear ribonucleoprotein K (hnRNPK), which positively regulates lncRNA-OG transcriptional activity. The authors hope that their findings will boost the clinical application of BM-MSC in osteogenic applications.

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!

November 6,2018 What’s the Stem Cells Buzz this Week? - Organelle Transfer, Cartilage Chondroprogenitors, Stem Cell Migration, and iPSC Therapy for SCI!

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

Intercellular Communication via Organelle Transfer by Stem Cells

An article from Lisa MA Murray and Anna D Krasnodembskaya (Queen's University Belfast, UK) focuses on the known instances of organelle transfer between stem cells and differentiated cells, what effects it has on recipient cells, and how organelle transfer is regulated. Within the last decade, there has been considerable interest in the inter‐cellular communication mediated by the transfer of cytoplasmic material and organelles between cells, and this STEM CELLS review aspires to provide a succinct overview of the numerous studies that have demonstrated how mitochondria and lysosomes are transported between cells by various mechanisms, including tunneling nanotubes, microvesicles, and cellular fusion.

Cartilage Chondroprogenitors Bridge the Meniscus

Tears in the inner one‐third of the meniscus heal poorly and present a significant clinical challenge; however, researchers from the laboratory of Chathuraka T. Jayasuriya (Brown University/Rhode Island Hospital, Providence, Rhode Island, USA) hypothesized that progenitor cells from healthy human articular cartilage (C‐PCs) could mediate bridging and reintegration of fibrocartilage tissue tears. In a new STEM CELLS article, the team now report that chondroprogenitor cell lines generated from healthy human articular cartilage facilitate successful bridging of inner meniscal tears in a manner that relies on SDF-1/CXCR4 chemokine axis. The authors hope that this research will provide proof-of-concept that C-PCs can reintegrate and repair fibrocartilaginous tissue.

The Mechanism of Activin B in Bone Marrow Stem Cell Migration

Previous research from the lab of Lin Zhang and Lu Zhang (Southern Medical University, Guangzhou, China) demonstrated that Activin B represents a potent chemoattractant for bone marrow‐derived mesenchymal stromal cells (BMSCs) and that  RhoA activation plays a key role. Now, the team returns with a STEM CELLS report in which the importance of membrane ruffle formation, microtubule morphology and focal adhesion signaling dynamics to Activin B induced BMSC migration. The team anticipates that their work will aid the optimization of MSC-based transplantation strategies in clinical skin wound healing.

iPSC-based Cell Therapy for Spinal Cord Injury

A recent article from the laboratory of Hideyuki Okano (Keio University School of Medicine, Tokyo, Japan) describes the preparation for a first‐in‐human clinical study of an induced pluripotent stem cell (iPSC)‐based cell transplant intervention for subacute spinal cord injury. Tsuji et al. address the issues of safety and tumorigenesis as well as practical problems that must be overcome to enable the development of therapeutic interventions for patients with chronic SCI. See STEM CELLS now for more on this Class I regenerative medicine protocol, as provided for under Japan's Act on the Safety of Regenerative Medicine, employing neural stem/progenitor cells derived from a clinical‐grade, integration‐free human “iPSC stock” generated by the Kyoto University Center for iPS Cell Research and Application.

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!

November 1,2018 What’s the Stem Cells Buzz this Week? - PARP Inhibition and Chemosensitivity, Xist Intron 1 in Reprogramming, BIN1 and hESC-CMs, and lncHOXC-AS3 in Osteogenesis!

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

PARP Inhibition and Chemosensitivity in Colorectal Cancer‐initiating Cells

Cancer‐initiating cells (CICs) contribute to the relapse of colon tumorigenesis, a leading killer in the US that suffers from resistance to treatments. In a new STEM CELLS study, researchers from the labs of Matthew F. Kalady (Case Western Reserve University, Cleveland, Ohio, USA) and Jeremy N Rich (University California, San Diego, California, USA) report that patient‐derived CICs display relative chemoresistance compared to differentiated progeny, although conventional cell lines failed to model therapeutic resistance. However, Jarrar et al. discovered that inhibition of poly‐ADP‐ribose polymerase (PARP), a critical single‐strand break repair mediator, sensitized CICs to chemotherapy, suggesting that a novel combinatorial strategy may serve as an effective means to treat colon cancer.

The Role of Xist Intron 1 in Somatic Cell Reprogramming

A recent STEM CELLS study from the labs of Pentao Liu (Wellcome Trust Sanger Institute, Cambridge, UK) and Xihe Li (Inner Mongolia University, Hohhot, China) sought to understand the role of Xist, the master regulator of X chromosome inactivation (XCI), in the reprogramming process through the activity of transcription‐factor‐like effectors (TALE)‐based designer transcriptional factors (dTFs). Zhang et al. discovered that binding of a repressive dTF to intron 1 of Xist in somatic cells did not affect Xist expression; however, the epigenetic perturbations led to substantial improvements in induced pluripotent stem cell generation and somatic cell nuclear transfer preimplantation embryo development. The authors anticipate that their findings may provide a unique route to reprogramming.

BIN1 promotes Generation of hESC-Cardiomyocytes with Ventricular Phenotype

The production of mature cardiomyocytes from human embryonic stem cells (hESC-CMs) will impact both cell therapies for cardiac disease and disease modeling. Now, researchers from the labs of Claudia M. Moreno and Luis Fernando Santana (University of California, Davis, California, USA) have revealed that the expression of Bridging Integrator 1 (BIN1) facilitates the production of mature ventricular-like cardiomyocytes by regulating the formation of T-tubules and adult-like Ca2+ release units. De la Mata et al. hope that this new advance will generate cells better suited to both regenerative therapy and modeling. See STEM CELLSnow to discover more!

Role of lncHOXC-AS3 in MSC Osteogenesis

Mesenchymal stem cells (MSCs) derived from multiple myeloma (MM) patients display impaired osteogenic differentiation, although the molecular mechanisms involved remain unknown. Now, a new STEM CELLS study led by Wenzhuo Zhuang and Yongsheng Zhang (Soochow University, Suzhou, China) has established that MM‐MSCs specifically overexpress the bioactive lncRNA HOXC‐AS3, which interacts with HOXC10, increases HOXC10 stability, and promotes HOXC10 expression, thereby repressing osteogenesis in MM‐MSCs. Li et al. hope that their study demonstrates the potential clinical significance of lncRNA HOXC‐AS3 as a therapeutic target for bone disease in MM.

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!

October 28,2018 What’s the Stem Cells Buzz this Week? - Cyclosporine’s Effect on ECFCs, Reviewing CSC Targeted Therapies, HSPCs as Immunomodulators in Cancer, and the Development of Carcinoma-associated MSCs!

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

Deleterious Effect of Cyclosporine on Endothelial Colony Forming Cells

The application of immunosuppressive compounds, such as cyclosporine, aims to improve allogeneic stem cell engraftment; however, can this impact stem cell function? Researchers from the group of Jatin Patel (University of Queensland, Australia) assessed the consequence of cyclosporine treatment on hindlimb revascularization via the application of endothelial colony forming cells (ECFC) and mesenchymal stem cells (MSC). Interestingly, the team discovered a deleterious effect of the immunosuppressive agent on the function and survival of ECFCs in vivo. Sim et al. believe that their new findings, published inSTEM CELLS Translational Medicine, will have significant clinical implications for allogeneic stem cell therapies treating ischemic disease.

Reviewing Cancer Stem Cell Targeted Therapies

A new concise review from the lab of Stanton L. Gerson (Case Western Reserve University, Cleveland, Ohio USA) summarizes ongoing preclinical and clinical efforts to therapeutically target cancer stem cells (CSCs), a distinct subpopulation of tumor cells implicated in therapy resistance and metastasis. This STEM CELLS Translational Medicine article from Desai et al. reviews signaling pathways involved in cancer stem cell maintenance and highlights novel approaches, such as epigenetic targeting and immunotherapy, that hold promise for improving patient outcomes.

Hematopoietic Stem and Progenitor cells as Immunomodulators in Cancer

Our next review article from the laboratory of Catherine T. Flores (University of Florida, Gainesville, Florida, USA) highlights studies into a critical role for hematopoietic stem and progenitor cells (HPSCs) as modulators of cancer immunity that could be incorporated into cellular immunotherapy strategies. Writing in STEM CELLS, Wildes et al. discuss both the immunosuppressive role of HSPCs during solid malignancies and the recent studies that uncovered immune‐activating HSPCs and progeny. Sounds like a great read!

Carcinoma‐associated Mesenchymal Stem Cells Arise from Tissue-specific Normal Stroma

Carcinoma‐associated mesenchymal stem cells (CA‐MSCs), critical stromal progenitor cells within the tumor microenvironment, promote tumor cell growth while increasing cancer “stemness” and chemotherapeutic resistance. Recent research from the lab of Lan G. Coffman (University of Pittsburgh, Pittsburgh, PA, USA) applied RNA sequencing of normal omental MSCs and ovarian CA‐MSCs to create a unique predictive algorithm to classify CA‐MSCs. By applying this model, the team definitively demonstrate that ovarian CA‐MSCs arise from tumor-mediated reprogramming of local tissue MSCs, thereby providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. See STEM CELLS now for a fascinating read.

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!

October 15,2018 What’s the Stem Cells Buzz this Week? - Priming MSCs, Stressing CESCs, Modeling Cardiac Disease, and Regenerating the Kidney!

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

Nitric Oxide-primed Mesenchymal Stem Cells Boost Engraftment

The ex vivo manipulation of hematopoietic stem cells (HSCs) to improve their engraftment ability generally employs bone marrow‐derived mesenchymal stem cells (MSCs) as a feeder cell layer. Recent research from the group of Vaijayanti Kale (National Centre for Cell Science, Pune, India) highlighted the influencing role of AKT signaling in MSCs on HSC functionality. Now, the team returns with a new STEM CELLS study, where they demonstrate that the nitric oxide primed MSCs significantly boost engraftment of HSCs via intercellular transfer of microvesicles harboring mRNAs encoding HSC‐supportive genes. Jalnapurkar et al. hope that their findings will soon help to improve transplantation efficacy in human patients suffering from a range of disorders.

Inflammation and Hyperosmotic Stress on Corneal Epithelial Stem Cells

A recent study from the laboratory of Qingjun Zhou (Shandong Academy of Medical Sciences, Qingdao, China) investigated the effects of inflammation and hyperosmotic stress on corneal epithelial stem cells (CESCs) and corneal epithelial wound healing. Yang et al. report that compared with an IL‐1β or TNF‐α induced inflammatory environment, hyperosmotic stress caused persistent impairment on corneal epithelial stem/progenitor cells by inducing more severe cell apoptosis, necrosis, and G2/M ‐arrest of the cell cycle, thereby causing more serious epithelial wound healing delay. See STEM CELLS Translational Medicine now to discover how these findings provide the cellular basis for the strict control of inflammation and dry eye before clinical limbal stem cell transplantation.

Reviewing Human in vitro Cardiac Disease Modeling

The generation and directed differentiation of human induced pluripotent stem cells (hiPSCs) have provided a means for obtaining virtually unlimited amounts of patient‐derived cardiomyocytes, while major advances in gene editing techniques have enabled the targeted mutation of specific genes, which could result in the introduction of aberrant or restored gene function. A review from the group of Peter van der Meer (University Medical Center Groningen, Groningen, Netherlands) now highlights the impact and applications of these state‐of‐the‐art techniques in the field of heart failure. See STEM CELLS Translational Medicine now for an update on this new era of in vitro cardiac disease modeling.

Reviewing Stem Cell-mediated Approaches For Kidney Regeneration

A fascinating new review article from Laura Perin (Children's Hospital Los Angeles, California, USA) discusses stem cell products as potential therapies for kidney diseases, with a firm focus on apparent discrepancies in the literature that contribute to difficulty in translating renal regenerative therapies. Marcheque et al. propose that harmonized rigorous protocols for characterization, handling, and delivery of stem cells could significantly advance the field and present details of suggested approaches to foster translation in the field of renal regeneration. See STEM CELLS Translational Medicine to read more on how the coordination of methodologies (standardization) and long‐lasting collaborations to improve protocols and models will lead to reproducible, interpretable, high‐quality preclinical data.

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!

October 11,2018 What’s the Stem Cells Buzz this Week? - Mouse ESC Heterogeneity, human MSC Immunosuppression, Leydig Stem Cell Autografting, and MSC Proangiogenic Efficacy!

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

Histone Acetyltransferase-mediated Regulation of Mouse ESCs Heterogeneity

While many studies have indicated a probable link between mouse embryonic stem cell (mESC) fate decisions and increased transcriptional heterogeneity, we know little regarding the underlying controlling molecular mechanisms. Now, researchers led by Cristina Pina (University of Cambridge, UK) have established that inhibition of the Kat2a histone acetyltransferase leads to increased transcriptional heterogeneity in mESCs and an increased probability of exit from pluripotency. Overall, this STEM CELLS article links chromatin modification and transcriptional heterogeneity to cell fate decisions and highlights the importance of these links to a better understanding of development and disease.

Metabolism Underpins Human Mesenchymal Stem Cell Immunosuppression

Recent research has highlighted the ability of human mesenchymal stem cells (hMSCs) to actively reconfigure their metabolism to boost tissue repair, although quite how hMSCs regulate their energy metabolism to support immunomodulation remains mostly unknown. Now, scientists from the lab of Teng Ma (Florida State University, Tallahassee, FL, USA) have demonstrated that hMSC immune polarization by interferon‐gamma (IFN‐γ) treatment leads to a remodeling of hMSC metabolic pathways toward glycolysis (required for the secretion of immunosuppressive factors) and highlighted the importance of the Akt/mTOR signaling pathway. Overall, Liu et al. hope that their STEM CELLS Translational Medicine article now demonstrates the potential of altering hMSC metabolism to enhance their immunomodulatory properties and therapeutic efficacy in various diseases.

Subcutaneous Leydig Stem Cell Autografts for Testosterone Deficiency Treatment

Leydig stem cell (LSC) transplantation represents a possible alternative to the currently problematic exogenous testosterone therapies employed to treat testosterone deficiency; however, testicular injection of LSCs is not clinically feasible. Now, research led by Ranjith Ramasamy (University of Miami, Miami, Florida, USA) and published in STEM CELLS Translational Medicine examined the feasibility of subcutaneously autografting LSCs in combination with Sertoli and myoid cells to increase testosterone levels. Excitingly, Arora et al. now demonstrate that this approach is safe and effective for men with low testosterone who desire fertility preservation; the authors suggest that this therapy may represent a paradigm shift in this area.

 

Biomarker of Mesenchymal Stem Cells for Proangiogenic Efficacy

The clinical application of mesenchymal stem cells (MSCs) for the treatment of ischemic disease currently suffers from poor cell engraftment and inconsistent stem cell potency. However, exciting new research from the lab of Young Ae Joe (Catholic University of Korea, Seoul, Korea) has now established efficient biomarkers for the prediction of vascular regenerative efficacy in the treatment of ischemic diseases. Kim et al. sought correlations between secretion profile of paracrine factors in vitro with in vivo pro-angiogenic activities and uncovered angiogenin, interleukin-8 (IL8), monocyte chemoattractant protein-1 (MCP1), and vascular endothelial growth factor (VEGF) as important factors. For all the details on this exciting advance, head over to STEM CELLS Translational Medicine now!

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!

October 7,2018 What’s the Stem Cells Buzz this Week? - Fibrotic Liver Regeneration, Reviewing Tooth Initiation, Corneal SOX2 Expression via CRISPR, and Epigenetic Regulation of MSC Fate!

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

A Novel Accelerator of Fibrotic Liver Regeneration

While Granulocyte‐colony stimulating factor (G‐CSF) can mobilize and enhance the proliferation of hepatic progenitor cells (HPC) to ameliorate impaired liver function, the exact mechanisms at play remain unknown. Now, researchers from the group of Yutaka Inagaki (Tokai University, Kanagawa, Japan) have identified opioid growth factor receptor-like‐1 (OGFRL1) as a novel bone marrow cell‐derived accelerator of fibrotic liver regeneration in response to G‐CSF treatment. Yanagawa et al. hypothesize that the administration of cells overexpressing OGFRL1 may serve as a regenerative therapy for advanced liver fibrosis; discover more at STEM CELLS now!

Cellular and Molecular Mechanisms Regulating Tooth Initiation

A new review article from Anamaria Balic (University of Helsinki, Finland) aims to provide an overview of the molecular and cellular mechanisms that guide the initial stages of tooth development and outline potential obstacles. While studies have unraveled many layers of the molecular regulation of tooth development, regulation of the initial stages of tooth development, as well as the cellular mechanisms that govern tooth development, remain mostly unknown. See STEM CELLS for more.

SOX2 Activation Using CRISPR Activation

Human corneal endothelial cells (hCECs) do not regenerate, thereby representing a problem for those suffering from corneal endothelial diseases. For these reasons, esearchers from the lab of Young Joo Shin (Hallym University College of Medicine, Seoul, Korea) set out circumnavigate this problem. Now, Chang et al. report that CRISPR activation mediated overexpression of SOX2 in the corneal endothelium of Sprague–Dawley rats promoted wound healing and regeneration. Does CRISPR activation hold the key to treating corneal endothelial disease? Head over to STEM CELLS now to discover more!

Ash1l Regulates Mesenchymal Stem Cell Fate Decision

Following the discovery that loss of the Ash1l histone methyltransferase can lead to arthritis with more severe cartilage and bone destruction, researchers from the lab of Ling Ye (Sichuan University, Chengdu, China) sought to document the function of Ash1l in skeletal formation. Reporting in STEM CELLS, Yin et al. now demonstrate a positive correlation between bone mass and the expression of Ash1l, with histone methyltransferase activity playing a significant role. The authors anticipate that their findings will prompt the development of new therapeutic strategies to promote osteogenesis.

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!

October 4,2018 What’s the Stem Cells Buzz this Week? - miRNA and Mammary Stem Cells, Enhanced MSC Immunosuppression, Endothelial MSC Plasticity, and hPSC Modelling of Beta-Cell Pathology!

The Stem Cells Portal brings you a roundup of some of the new and exciting stories in the ever-changing world of stem cells, regenerative medicine, and beyond!

Role of miR-205 in Mammary Stem Cells

A new study from the lab of Jeffrey M. Rosen (Baylor College of Medicine, Houston, Texas, USA) recently highlighted an essential role for microRNA-mediated regulation of the stem cell self‐renewal and differentiation required for mammary gland development. Lu et al. discovered that deletion of miR-205 abrogated mammary stem cell self-renewal during mammary reconstitution and that negative regulators of YAP and WNT signaling represented novel miR-205 targets. For all the details, see STEM CELLS now!

Serum-Free Mesenchymal Stem Cells Enhance Immunosuppressive Effects

A fascinating recent report out of the Ayumu Nakashima and Takao Masaki (Hiroshima University, Hiroshima, Japan) lab has recently demonstrated that the serum present in culture medium can inhibit the immunosuppressive and antifibrotic abilities of in vitro expanded mesenchymal stem cells (MSCs) and, therefore, hinder their clinical application. Yoshida et al. report in STEM CELLS Translational Medicine how serum-free growth conditions enhanced the ability of MSCs to induce an immunosuppressive M2 in macrophages and promoted the amelioration of renal fibrosis when compared MSCs cultured in serum‐containing conditions. Overall, this study promotes the use of serum‐free culture medium for the culture of clinically applied MSCs.

Endothelial Plasticity of Adipose-derived Mesenchymal Stem Cells

While many hope that adipose‐derived mesenchymal stem cells (ASCs) may represent endothelial cell substitutes for the vascularization of tissue‐engineered constructs, new research from the lab of J. Paul Santerre (University of Toronto, Ontario, Canada) may have now dashed this line of research. Antonyshyn et al. now report that ASCs present with a “strikingly limited” endothelial differentiation potential even though differentiating ASCs upregulated the expression of endothelial genes and proteins. Will this study end the endothelial promise of ASCs? Head over to STEM CELLS Translational Medicine to discover more!

Human Pluripotent Stem Cell Modelling of Pancreatic Beta-Cell Pathology

Finally, a new review article from the lab of Timo Otonkoski (University of Helsinki, Finland) aims to summarize current progress in modeling diabetes with human pluripotent stem cells (hPSCs). Balboa et al. discuss the current challenges and opportunities of these approaches to dissect pancreatic beta‐cell pathology and devise new pharmacological and cell replacement therapies. For a tremendous sounding read, STEM CELLS has you covered!

That’s a wrap for now! Please feel free to leave a comment and discuss the papers covered here on the Stem Cells Buzz. Happy reading!