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Stem Cells

Sacha M L Khong, Ming Lee, Nina Kosaric, Danika M Khong, Yixiao Dong, Ursula Hopfner, Matthias M Aitzetmüller, Dominik Duscher, Richard Schäfer, Geoffrey C Gurtner
Although bone marrow-derived mesenchymal stem cells (BM-MSCs) are widely recognized as promising therapeutic agents, the age-related impacts on cellular function remain largely uncharacterized. In this study, we found that BM-MSCs from young donors healed wounds in a xenograft model faster compared with their aged counterparts (p < .001). Given this significant healing advantage, we then used single-cell transcriptomic analysis to provide potential molecular insights into these observations. We found that the young cells contained a higher proportion of cells characterized by a higher expression of genes involved in tissue regeneration...
November 9, 2018: Stem Cells
Vera J Mehler, Chris J Burns, Melanie L Moore
With their immunosuppressive features, human Mesenchymal Stromal Cells (MSCs), sometimes also termed mesenchymal stem cells, hold great potential as a cell-based therapy for various immune-mediated diseases. Indeed, MSCs have already been approved as a treatment for Graft versus Host Disease (GvHD). However, contradictory data from clinical trials and lack of conclusive proof of efficacy, hinder the progress toward wider clinical use of MSCs and highlight the need for more relevant disease models. Humanized mice are increasingly used as models to study immune-mediated disease, as they simulate human immunobiology more closely than conventional murine models...
November 5, 2018: Stem Cells
Julie R Beegle
No abstract text is available yet for this article.
November 5, 2018: Stem Cells
YeonSung Son, Sang-Mo Kwon, Je-Yoel Cho
Endothelial progenitor cells (EPCs) provide an important source of recovery from blood vessel dysfunction. Late endothelial progenitor cells (LEPCs) are circulating blood cells that are capable of promoting vascular repair. Using transcriptome analysis, we identified distinctive LEPC profiles and found that CD276 (B7-H3) mRNA is strongly expressed in LEPCs. CD276 protein is present abundantly on the cell surface of LEPC when analyzed by FACS and immunocytochemistry. CD276, a B7 family member, is a type I transmembrane glycoprotein...
October 31, 2018: Stem Cells
Yeela Shamai, Dalia Cohn Alperovich, Zohar Yakhini, Karl Skorecki, Maty Tzukerman
The interactions of Cancer Stem Cells (CSC) within the tumor microenvironment (TME), contribute to the overall phenomenon of intra-tumoral heterogeneity, which also involve CSC interactions with non-cancer stromal cells. Comprehensive understanding of the tumorigenesis process requires elucidating the coordinated gene expression between cancer and tumor stromal cells for each tumor. We show that human gastric cancer cells (GSC1) subvert gene expression and cytokine production by mesenchymal stem cells (GSC-MSC), thus promoting tumor progression...
October 31, 2018: Stem Cells
Shaunak S Adkar, Chia-Lung Wu, Vincent P Willard, Amanda Dicks, Adarsh Ettyreddy, Nancy Steward, Nidhi Bhutani, Charles A Gersbach, Farshid Guilak
The differentiation of human induced pluripotent stem cells (hiPSCs) to prescribed cell fates enables the engineering of patient-specific tissue types, such as hyaline cartilage, for applications in regenerative medicine, disease modeling, and drug screening. In many cases, however, these differentiation approaches are poorly controlled and generate heterogeneous cell populations. Here, we demonstrate cartilaginous matrix production in three unique hiPSC lines using a robust and reproducible differentiation protocol...
October 31, 2018: Stem Cells
Jiejia Xu, Peter J Gruber, Kenneth R Chien
Understanding stage-specific molecular mechanisms of human cardiomyocyte progenitor formation and subsequent differentiation are critical to identify pathways that might lead to congenital cardiovascular defects and malformations. In particular, gene mutations in the TGF-β superfamily signaling pathways can cause human congenital heart defects, and murine loss of function studies of a central component in this pathway, Smad4, leads to early embryonic lethality. To define the role of SMAD4 at the earliest stages of human cardiogenesis, we generated SMAD4 mutant human embryonic stem cells (hESC)...
October 30, 2018: Stem Cells
Kilsoo Jeon, Dhirendra Kumar, Amanda E Conway, Kyeyoon Park, Raja Jothi, Anton M Jetten
Anterior-posterior (A-P) specification of the neural tube involves initial acquisition of anterior fate followed by the induction of posterior characteristics in the primitive anterior neuroectoderm. Several morphogens have been implicated in the regulation of A-P neural patterning; however, our understanding of the upstream regulators of these morphogens remains incomplete. Here, we show that the Krüppel-like zinc finger transcription factor GLI-Similar 3 (GLIS3) can direct differentiation of human embryonic stem cells (hESCs) into posterior neural progenitor cells (NPCs) in lieu of the default anterior pathway...
October 30, 2018: Stem Cells
Xiaomeng Zhang, Huaning Xie, Pan Chang, Huishou Zhao, Yunlong Xia, Ling Zhang, Xiong Guo, Chong Huang, Feng Yan, Lang Hu, Chen Lin, Yueyang Li, Zhenyu Xiong, Xiong Wang, Guohua Li, Longxiang Deng, Shan Wang, Ling Tao
Smooth muscle cells (SMCs), which form the walls of blood vessels, play an important role in vascular development and the pathogenic process of vascular remodeling. However, the molecular mechanisms governing SMC differentiation remain poorly understood. Glycoprotein M6B (GPM6B) is a four-transmembrane protein that belongs to the proteolipid protein family and is widely expressed in neurons, oligodendrocytes and astrocytes. Previous studies have revealed that GPM6B plays a role in neuronal differentiation, myelination and osteoblast differentiation...
October 29, 2018: Stem Cells
Su'an Tang, Zhongyu Xie, Peng Wang, Jinteng Li, Shan Wang, Wenjie Liu, Ming Li, Xiaohua Wu, Hongjun Su, Shuizhong Cen, Guiwen Ye, Guan Zheng, Yanfeng Wu, Huiyong Shen
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the main source of osteoblasts in vivo and are widely used in stem cell therapy. Previously, we analyzed long noncoding RNA (lncRNA) expression profiles during BM-MSC osteogenesis, and further investigation is needed to elucidate how lncRNAs regulate BM-MSC osteogenesis. Herein, we used customized microarrays to determine lncRNA expression profiles in BM-MSCs on days 0 and 10 of osteogenic differentiation. In addition, we identified a novel osteogenesis-associated lncRNA (lncRNA-OG) that is upregulated during this process...
October 29, 2018: Stem Cells
Marta Vilà-González, Sophia Kelaini, Corey Magee, Rachel Caines, David Campbell, Magdalini Eleftheriadou, Amy Cochrane, Daiana Drehmer, Marianna Tsifaki, Karla O'Neill, Edoardo Pedrini, Chunbo Yang, Reinhold Medina, Denise McDonald, David Simpson, Anna Zampetaki, Lingfang Zeng, David Grieve, Noemi Lois, Alan W Stitt, Andriana Margariti
The mortality rate for (cardio)-vascular disease is one of the highest in the world, so a healthy functional endothelium is of outmost importance against vascular disease. In this study, human induced pluripotent stem (iPS) cells were reprogrammed from 1 ml blood of healthy donors and subsequently differentiated into endothelial cells (iPS-ECs) with typical EC characteristics. This research combined iPS cell technologies and next-generation sequencing to acquire an insight into the transcriptional regulation of iPS-ECs...
October 29, 2018: Stem Cells
Anastasia Lomova, Danielle N Clark, Beatriz Campo-Fernandez, Carmen Flores-Bjurström, Michael L Kaufman, Sorel Fitz-Gibbon, Xiaoyan Wang, Eric Y Miyahira, Devin Brown, Mark A DeWitt, Jacob E Corn, Roger P Hollis, Zulema Romero, Donald B Kohn
CRISPR/Cas9-mediated gene editing of human hematopoietic stem cells (hHSCs) is a promising strategy for the treatment of genetic blood diseases through site-specific correction of identified causal mutations. However, clinical translation is hindered by low ratio of precise gene modification using the corrective donor template (homology-directed repair, HDR) to gene disruption (non-homologous end joining, NHEJ) in hHSCs. By using a modified version of Cas9 with reduced nuclease activity in G1 phase of cell cycle when HDR cannot occur, and transiently increasing the proportion of cells in HDR-preferred phases (S/G2), we achieved a four-fold improvement in HDR/NHEJ ratio over the control condition in vitro, and a significant improvement after xenotransplantation of edited hHSCs into immune-deficient mice...
October 29, 2018: Stem Cells
Osahiko Tsuji, Keiko Sugai, Ryo Yamaguchi, Syoichi Tashiro, Narihito Nagoshi, Jun Kohyama, Tsuyoshi Iida, Toshiki Ohkubo, Go Itakura, Miho Isoda, Munehisa Shinozaki, Kanehiro Fujiyoshi, Yonehiro Kanemura, Shinya Yamanaka, Masaya Nakamura, Hideyuki Okano
There have been numerous attempts to develop stem cell transplantation approaches to promote the regeneration of spinal cord injuries (SCI). Our multi-center team is currently planning to launch a first-in-human clinical study of an induced pluripotent stem cell (iPSC)-based cell transplant intervention for subacute SCI. This trial will be conducted as Class I regenerative medicine protocol as provided for under Japan's Act on the Safety of Regenerative Medicine (ASRM), using 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 (CiRA)...
October 29, 2018: Stem Cells
Chathuraka T Jayasuriya, John Twomey-Kozak, Jake Newberry, Salomi Desai, Peter Feltman, Jonathan R Franco, Neill Li, Richard Terek, Michael G Ehrlich, Brett D Owens
Meniscus injuries are among the most common orthopedic injuries. Tears in the inner one-third of the meniscus heal poorly and present a significant clinical challenge. In this study, we hypothesized that progenitor cells from healthy human articular cartilage (chondroprogenitor cells [C-PCs]) may be more suitable than bone-marrow mesenchymal stem cells (BM-MSCs) to mediate bridging and reintegration of fibrocartilage tissue tears in meniscus. C-PCs were isolated from healthy human articular cartilage based on their expression of mesenchymal stem/progenitor marker activated leukocyte cell adhesion molecule (ALCAM) (CD166)...
October 24, 2018: Stem Cells
Xueer Wang, Pei Tang, Fukun Guo, Min Zhang, Yuan Yan, Mianbo Huang, Yinghua Chen, Lu Zhang, Lin Zhang
In a previous study, we have shown that Activin B is a potent chemoattractant for bone marrow-derived mesenchymal stromal cells (BMSCs). As such, the combination of Activin B and BMSCs significantly accelerated rat skin wound healing. In another study, we showed that RhoA activation plays a key role in Activin B-induced BMSC migration. However, the role of the immediate downstream effectors of RhoA in this process is unclear. Here, we demonstrated that mammalian homolog of Drosophila diaphanous-1 (mDia1), a downstream effector of RhoA, exerts a crucial function in Activin B-induced BMSC migration by promoting membrane ruffling, microtubule morphology, and adhesion signaling dynamics...
October 24, 2018: Stem Cells
Lisa Ma Murray, Anna D Krasnodembskaya
The therapeutic potential of stem cell-based therapies may be largely dependent on the ability of stem cells to modulate host cells rather than on their differentiation into host tissues. 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. Numerous studies have shown that mitochondria and lysosomes are transported between cells by various mechanisms, such as tunnelling nanotubes, microvesicles and cellular fusion...
October 24, 2018: Stem Cells
Ana De La Mata, Sendoa Tajada, Samantha O'Dwyer, Collin Matsumoto, Rose E Dixon, Nirmala Hariharan, Claudia M Moreno, L Fernando Santana
Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are at the center of new cell-based therapies for cardiac disease, but may also serve as a useful in vitro model for cardiac cell development. An intriguing feature of hESC-CMs is that although they express contractile proteins and have sarcomeres, they do not develop transverse-tubules (T-tubules) with adult-like Ca2+ release units (CRUs). We tested the hypothesis that expression of the protein BIN1 in hESC-CMs promotes T-tubules formation, facilitates CaV 1...
October 23, 2018: Stem Cells
Tyler J Wildes, Catherine T Flores, Duane A Mitchell
Hematopoietic stem and progenitor cells (HSPCs) are the progenitor cells that can regenerate the entire blood compartment, including the immune system. Recent studies have unearthed considerable immune-modulating potential of these cells. They can migrate through chemotactic gradients, differentiate into functional immune cells, and cross-talk with immune cells during infections, autoimmune diseases, and cancers. While the primary role of HSPCs during solid malignancies is considered immunosuppressive, recent studies have discovered immune-activating HSPCs and progeny...
October 23, 2018: Stem Cells
Lan G Coffman, Alexander T Pearson, Leonard G Frisbie, Zachary Freeman, Elizabeth Christie, David D Bowtell, Ronald J Buckanovich
Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment (TME). We previously demonstrated that CA-MSCs differentially express bone morphogenetic protein family members, promote tumor cell growth, increase cancer "stemness," and chemotherapy resistance. Here, we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate global changes in CA-MSC gene expression. Using these expression profiles, we create a unique predictive algorithm to classify CA-MSCs...
October 23, 2018: Stem Cells
Awad Jarrar, Fiorenza Lotti, Jennifer DeVecchio, Sylvain Ferrandon, Gerald Gantt, Adam Mace, Georgios Karagkounis, Matthew Orloff, Monica Venere, Masahiro Hitomi, Justin Lathia, Jeremy N Rich, Matthew F Kalady
Colorectal cancer remains a leading killer in the United States with resistance to treatment as the largest hurdle to cure. Colorectal cancer-initiating cells (CICs) are a self-renewing tumor population that contribute to tumor relapse. Here, we report that patient-derived CICs display relative chemoresistance compared to differentiated progeny. In contrast, conventional cell lines failed model therapeutic resistance. CICs preferentially repaired chemotherapy-induced DNA breaks, prompting us to interrogate DNA damage pathways against which pharmacologic inhibitors have been developed...
October 23, 2018: Stem Cells
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