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

December 13, 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

December 10,2018 What’s the Stem Cells Buzz this Week? - Stem Cell Mobilization, Skeletal Stem Cell Migration, Suicide System for Stem Cell Therapy, and Cystic Fibrosis Cell Therapy!

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!

Chemotactic Tripeptide-Induced Mobilization of Angiogenic Stem Cells

A new study from the lab of Jae Ho Kim (Pusan National University School of Medicine, Yangsan, Republic of Korea) recently sought to understand how a collagen‐derived chemotactic tripeptide (Ac-PGP) mobilizes circulating angiogenic cells (CACs) from the bone marrow to contribute to the treatment of peripheral artery diseases. Employing a murine hindlimb ischemia model, Kwon et al. discovered that Ac-PGP stimulated blood perfusion and prevented limb amputation by promoting the mobilization of CACs through a CXCR2‐dependent mechanism. For more details on how this knowledge could lead to CAC‐mediated therapy for peripheral artery diseases, see STEM CELLS Translational Medicine now!

TAFA2 Neurokine Induces Skeletal Stem Cell Migration

Researchers from the lab of Abbas Jafari and Moustapha Kassem (University of Copenhagen, Denmark) hope to create a fuller understanding of the recruitment of human mesenchymal stem cells (hMSCs) to sites of tissue injury in order to develop more advanced regenerative therapies. In their new study, the team now demonstrate that the elevated expression of TAFA2, a recently discovered neurokine involved in neuronal cell migration and neurite outgrowth, at sites of skeletal fracture induces hMSC migration through activation of Rac1/p38 signaling. For more on the relevance of TAFA2 to regenerative medicine applications, see STEM CELLS now!

Suicide System in hiPSC-Neural Stem/Progenitor Therapy

The differentiation and transplantation of pluripotent derived cells carries a risk of tumorigenesis due to the presence of contaminating undifferentiated cells. Researchers from the labs of Hideyuki Okano and Masaya Nakamura (Keio University School of Medicine, Tokyo, Japan) recently introduced the herpes simplex virus type 1 thymidine kinase (HSVtk) gene into a human induced pluripotent stem cell‐derived neural stem/progenitor cell (hiPSC‐NS/PC) line known to undergo tumorigenic transformation. Encouragingly, the HSVtk system ablated all immature proliferating cells and permitted transplanted hiPSC‐NS/PC derivatives to safely return motor function to mice with injured spinal cords. Discover more at STEM CELLS Translational Medicine now!

Cell Therapy for Cystic Fibrosis Lung Disease

Previous studies from the lab of Susan D. Reynolds (Ohio State University, Columbus, Ohio, USA) that around 60 million human basal cells may be required to repopulate the human airway epithelium as a means to treat cystic fibrosis (CF) lung disease. The team now return with a new STEM CELLS Translational Medicine article in which they compare the proliferation potential of non‐CF and CF tissue‐derived bronchial basal cells. Overall, Hayes Jr. et al. demonstrate that non‐CF and CF basal cell proliferation is similar, CF basal cells can be amplified to a therapeutic cell dose, and amplified non‐CF and CF basal cell clones differentiate normally. However, cell amplification can deplete the regenerative basal cell pool. Overall, the authors hope that their findings will raise the possibility of cell therapy for CF.

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!

December 2,2018 What’s the Stem Cells Buzz this Week? - MSC-Mediated Polarization, Adherent Vitrification of hiPSCs, Validation of cGMP hPSCs, and cSrc-mediated Endoderm Commitment!

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!

Mesenchymal Stem Cell-Mediated Polarization Limits Carcinogenesis

A recent study from Alain Chapel (Institut de Radioprotection et de Sûreté Nucléaire, France) and Annette K. Larsen (Sorbonne Université, Paris, France) sought to determine the influence of mesenchymal stem cell (MSC) therapy on the progression of solid tumors by analyzing an immunocompetent rat model of human colorectal carcinogenesis. François et al. discovered that the transient presence of MSCs in the colon tissue of treated animals could inhibit cancer development by modulating the immune component of the tumor microenvironment, even one year after the last MSC administration. For all the details, see STEM CELLS Translational Medicine.

Adherent Vitrification of Human Induced Pluripotent Stem Cells and their Neural Derivatives

The efficient cryopreservation of human induced pluripotent stem cells (hiPSCs) represents an enormous challenge in research and regenerative medicine; however, a recent STEM CELLS Translational Medicine study tested whether a new method could improve immediate post‐thawing applicability. Researchers from the labs of Beate Winner (Friedrich‐Alexander‐Universität, Erlangen‐Nürnberg) and Julia C. Neubauer (Fraunhofer Institute for Biomedical Engineering, Sulzbach, Germany) that ultra‐fast cooling by adherent vitrification in the TWIST substrate (a device combining cultivation, vitrification, storage, and post‐thawing cultivation) improved direct post‐thaw applicability of hiPSCs as well as their neural derivatives. Kaindl et al. hope that their new method can be transferred to current stem cell research and can make large‐scale experiments more efficient and comparable.

Validation of Current Good Manufacturing Practice Pluripotent Stem Cells for Liver Therapy

Researchers from the lab of S. Tamir Rashid (King's College London, United Kingdom) recently sought to assess the production of hepatocytes from validated current good manufacturing practice (cGMP) human pluripotent stem cells for treatment of patients with liver disease. In their article, Blackford et al. report that employing a chemically defined four‐step hepatic differentiation protocol reproducibly and uniformly generated cells with advanced hepatic function potentially suitable for future therapeutic applications. For more on this first of its kind study, head over to STEM CELLS Translational Medicine now!

Critical role of c-Src in Human Endoderm Commitment of iPSCs

Research led by Yoon‐Young Jang (Johns Hopkins University School of Medicine, Baltimore, Maryland, USA) recently aimed to define vital molecular mediators in human liver development by testing tyrosine kinases inhibitors during hepatic differentiation of human induced pluripotent stem cells (iPSCs). Chaudhari et al. discovered the importance for the c‐Src protein kinase in endoderm formation: transient alteration of c‐Src activity in the early stage of liver development resulted in abnormal fibrotic‐biliary cells resembling those observed in patients with biliary fibrosis. For more on an advance that may provide a basis for establishing human‐specific experimental systems for assessing abnormal liver development, see STEM CELLS 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!

November 25,2018 What’s the Stem Cells Buzz this Week? - Fibrous Dysplasia Regulation, Allergic Asthma, Brain Neurogenesis, and MSC Adipo-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!

HDAC8 Pathway Regulates the Fibrous Phenotype Dysplasia

Bone marrow stem cells (BMSCs) in patients suffering from fibrous dysplasia (FD) display osteogenic defects, and we currently lack targeted therapeutic strategies. Researchers from the laboratory of Hongbing Jiang (Nanjing Medical University, Jiangsu Province, China) compared normal- and FD-BMSCs, discovering a significant role for the cAMP‐CREB1‐HDAC8 pathway in regulating biological characteristics of FD-BMSCs. Xiao et al. also noted that HDAC8 inhibition leads to significant therapeutic effects in an in vitro experimental model of FD and nude mice implanted with FD-BMSCs. For more, see STEM CELLS Translational Medicine now!

Therapeutic Effects of Mesenchymal Stem Cells in Allergic Asthma

New research from the lab of Patricia R.M. Rocco (Federal University of Rio de Janeiro, Brazil) recently assessed the ability of bronchoalveolar lavage fluid or serum from asthmatic mice to prime mesenchymal stem cells (MSCs) in the hope of improving their immunomodulatory properties in asthma treatment. In their new STEM CELLS Translational Medicine article, Abreu et al. used a house dust mite extract asthma mouse model to demonstrate that serum-exposed MSCs promoted the most significant reduction of inflammation and remodeling and the greatest improvement in lung function. The authors suggest that these positive findings may provide a platform for future clinical trials in patients with asthma.

Systemic Factors drive Brain Neurogenesis via Notch Ligand DLL4

New research from the lab of Lorraine Iacovitti (Thomas Jefferson University, Philadelphia, Pennsylvania, USA) recently reported that the leaky blood-brain barrier (BBB) in niches of the intact and stroke brain could respond to circulating VEGF165 to drive neural stem cell (NSC) activation and neurogenesis via the induction of the DLL4 Notch ligand in endothelial cells and pericytes. Lin et al. establish that enhanced DLL4-notch signaling and crosstalk between vasculature cells and NSCs regulates the activities of NSCs when triggered by systemic stroke-induced factors. For more details, see STEM CELLS now!

Smad4-Taz axis in Adipo-osteogenesis of Mesenchymal Stem Cells

In a new study assessing the factors that promote the differentiation of mesenchymal stem cells (MSCs), researchers from the laboratory of Seok Hee Park (Sungkyunkwan University, Suwon, South Korea) have highlighted the importance of the Smad4‐Taz axis in adipo‐osteogenesis. In their new study, Park et al. demonstrated that Smad4 plays a crucial role in the regulation of lineage commitment of MSCs, including human adipose tissue-derived stem cells (hASCs), into osteoblasts and adipocytes through modulating the retention of TAZ in the nucleus during MSC differentiation. Discover more at STEM CELLS 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!

November 18,2018 What’s the Stem Cells Buzz this Week? - Immunomodulatory MSCs, MSC Single-Cell Transcriptomics, OSC-mediated Facial Nerve Regeneration, and Islet Transplant in T1D!

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!

Immunomodulatory Mesenchymal Stem Cells in Humanized Mice

Contradictory clinical trial data and our incomplete grasp of immunosuppressive mechanisms represent significant obstacles in the widespread therapeutic application of human mesenchymal stem cells (MSCs). Now, a review article from the lab of Vera J. Mehler (NIBSC, South Mimms, UK) discusses humanized mice as a tool to develop a better comprehension of the mode of action of MSCs in mitigating the immune response in an in-vivo environment that closely resembles human immunobiology. This new STEM CELLS article describes how greater understanding may enable and encourage more studies employing humanized mice to investigate the immunomodulatory features of MSCs.

Single-Cell Transcriptomics of Human Mesenchymal Stem Cells

In order to better understand the age‐related impacts on bone marrow‐derived mesenchymal stem cell (BM‐MSC) function, researchers from the lab of Geoffrey C. Gurtner (Stanford University, Stanford, California, USA) compared wound healing in a xenograft model. Khong et al. discovered that younger BM-MSCs displayed higher expression of genes involved in tissue regeneration and this encouraged more rapid wound healing. Furthermore, this new STEM CELLS study also identified a unique, quiescent subpopulation exclusively present in young donor cells. Overall, the authors highlight a novel mechanism for the enhanced healing capacity of young stem cells, a finding that may have implications for autologous cell therapy in the elderly.

Olfactory Stem Cells with Hydrogel Accelerate Facial Nerve Regeneration

Researchers from the lab of Shinichi Esaki (Nagoya City University, Aichi, Japan) recently set out to test the ability of gelatin hydrogels to aid olfactory stem cells (OSCs) to treat facial nerve palsy. Reporting in STEM CELLS Translational Medicine, the authors discovered that cotransplantation of OSCs with a biodegradable hydrogel sponge enhanced peripheral nerve function and increased the number of regenerated nerve fibers in an established facial nerve palsy mouse model. The team anticipates that their research will aid the application of human OSCs as a means to accelerating recovery after facial nerve injury.

Islet Transplant Lessons for Stem Cell Therapy for Type 1 Diabetes

By examining data and patterns in registered clinical islet transplant studies for the treatment of type 1 diabetes (T1D), a team led by Marie Csete (Caltech Medical Engineering, Pasadena, California, USA) hoped to extract insights to apply in the design of a pluripotent stem cell‐derived islet therapy. In their new STEM CELLS Translational Medicine article, Welsch et al. report that while stem‐cell derived islets display the potential to treat a broader range of patients with type 1 diabetes than can be treated with current clinical protocols, the immunogenicity of allogeneic islets and the choice of optimal sites for transplantation remain open questions.

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 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!