Mesenchymal stem cells

  • Article
    | Open Access

    Cranial sutures are major growth centers for the skull vault and premature fusion leads to pathological fusion, craniosynostosis. Here the authors isolate Wnt responsive skeletal stem and progenitor cells from sutures, that can be transplanted together with Wnt3a protein to repair craniosynostosis in a mouse model.

    • Siddharth Menon
    • , Ankit Salhotra
    •  & Natalina Quarto
  • Article
    | Open Access

    Different types of mesenchymal progenitors participate in ectopic bone formation. Here, the authors show Col2+ lineage cells adopt a lymphatic endothelium cell fate, which regulates local inflammatory microenvironment after trauma, thus influencing heterotopic ossification (HO) development via a FGFR3-BMPR1a pathway.

    • Dali Zhang
    • , Junlan Huang
    •  & Yangli Xie
  • Article
    | Open Access

    Whether the adult testis harbours a somatic progenitor population is unknown. Here, the authors provide evidence that the testis interstitial cells expressing the transcription factor Tcf21 maintain adult testis homeostasis during aging, and act as potential reserve somatic progenitors following injury.

    • Yu-chi Shen
    • , Adrienne Niederriter Shami
    •  & Saher Sue Hammoud
  • Article
    | Open Access

    Bone regeneration involves activation of tissue resident stem cells. Here the authors show that mesenchymal progenitors from skeletal muscle mediate the fibrotic response to bone injury and also contribute to bone repair; processes that are impaired when both muscle and bone are injured.

    • Anais Julien
    • , Anuya Kanagalingam
    •  & Céline Colnot
  • Article
    | Open Access

    Fabrication of dynamic, reversible and biocompatible scaffolds with non-invasive external triggers has so far been limited. Here, the authors report on the creation of 3D printed scaffolds with Janus structure that produce nanovibrations when exposed to ultrasound, promoting bone regeneration.

    • Sandra Camarero-Espinosa
    •  & Lorenzo Moroni
  • Article
    | Open Access

    Unlike human teeth, mouse incisors grow throughout life, based on stem and progenitor cell activity. Here the authors generate single cell RNA-seq comparative maps of continuously-growing mouse incisor, non-growing mouse molar and human teeth, combined with lineage tracing to reveal dental cell complexity.

    • Jan Krivanek
    • , Ruslan A. Soldatov
    •  & Igor Adameyko
  • Article
    | Open Access

    Methods to generate beige adipocytes from a human cell source are inefficient. Here, the authors present a protocol that efficiently generates beige adipocytes from human adipose-derived stem cells (ADSCs), which have potential utility in therapeutic development relating to metabolic diseases such as type 2 diabetes.

    • Amar M. Singh
    • , Liang Zhang
    •  & Stephen Dalton
  • Article
    | Open Access

    Mouse incisor growth depends upon mesenchymal stromal cells (MSCs) and transit amplifying cells (TACs). Here the authors describe a distinct population of MSCs that is maintained by TACs through Dlk1 ligand and that contribute to MTACs and mesenchymal lineages including dental pulp and odontoblasts.

    • Jemma Victoria Walker
    • , Heng Zhuang
    •  & Bing Hu
  • Article
    | Open Access

    Prior evidence suggested mesenchymal stromal cells (MSCs) required for skeletal formation, maintenance, and repair arise postnatally. Here, the authors show that Hoxa11 lineage-marked cells give rise to all skeletal lineages from embryogenesis through adulthood and are upstream progenitors of LepR- and Osx-lineage MSCs

    • Kyriel M. Pineault
    • , Jane Y. Song
    •  & Deneen M. Wellik
  • Article
    | Open Access

    Mesenchymal cells contribute to tumor angiogenesis by regulating proliferation and migration of endothelial cells. Here, the authors show that mesenchymal stem cells also have the ability to acquire an endothelial phenotype upon TGF-β stimulation via the downstream kinase JNK, and that p38α negatively regulates this process.

    • Raquel Batlle
    • , Eva Andrés
    •  & Angel R. Nebreda
  • Article
    | Open Access

    Mutations in equilibrative nucleoside transporter 3 (ENT3), encoded by SLC29A3, cause a spectrum of human genetic disorders. Here, the authors show altered haematopoietic stem cell and mesenchymal stem cell fates in ENT3-deficient mice, due to misregulation of the AMPK-mTOR-ULK axis.

    • Sreenath Nair
    • , Anne M. Strohecker
    •  & Rajgopal Govindarajan
  • Article
    | Open Access

    Increased inflammation during ageing promotes osteoporosis by activating osteoclast function and inhibiting osteoblasts. Here, the authors show that TGFβ1 release from bone matrix during ageing induces degradation of TRAF3 in mesenchymal progenitor cells, leading to reduced osteoblast differentiation and increased osteoclast formation, and suggesting that pharmacological stabilization of TRAF3 could ameliorate age-related osteoporosis.

    • Jinbo Li
    • , Akram Ayoub
    •  & Brendan F. Boyce
  • Article
    | Open Access

    Cerebral cavernous malformation is a vascular disease characterized by capillary-venous cavernomas in the central nervous system. Here the authors show that cavernomas display benign tumor characteristics and originate from the clonal expansion of mutated endothelial progenitors which can attract surrounding wild-type cells, inducing their mesenchymal transition and leading to growth of the cavernoma.

    • Matteo Malinverno
    • , Claudio Maderna
    •  & Elisabetta Dejana
  • Article
    | Open Access

    In human adipose tissue (AT), adipocytes are organized into units of lobules. Here the authors identify distinct fibrous septal and stromal compartments within AT lobules that differ in composition and potential between subcutaneous and visceral regions and are disturbed in obesity and metabolic syndrome.

    • D. Estève
    • , N. Boulet
    •  & J. Galitzky
  • Article
    | Open Access

    Promising pilot clinical trials of mesenchymal stem cells (MSCs) therapy of lupus await validation in larger, controlled trials. Here the authors show that MSCs expand CD1c+ dendritic cells in cell culture by producing FLT3L, and that in lupus patients, circulating CD1c+ dendritic cells and FLT3L are increased following MSCs therapy.

    • Xinran Yuan
    • , Xiaodong Qin
    •  & Lingyun Sun
  • Article
    | Open Access

    Mesenchymal stem cells derived from dental pulp (DP-MSCs) differ in oncogenesic and developmental potential compared to those from bone marrow. Here, the authors show that decreased DNA methylation and histone H3K9Me2 enrichment along with higher PTEN activation in DP-MSCs promotes osteogenesis and reduces oncogenesis.

    • Wen-Ching Shen
    • , Yung-Chih Lai
    •  & Shih-Chieh Hung
  • Article
    | Open Access

    The incorporation of cells into tissue engineering scaffolds can be a major challenge. Here, the authors report on anchoring thrombin to cell membranes for the in situ formation of fibrin scaffolds around the modified cells, demonstrate scaffold formation in vitro and show cell survival in vivo.

    • Robert C. Deller
    • , Thomas Richardson
    •  & Adam W. Perriman
  • Article
    | Open Access

    The white pulp of spleen is an important immune structure dynamically modulated during development and immune responses. Here the authors define, using multi-color lineage tracing and single-cell transcriptome analysis, the subset distribution and differentiation trajectory of fibroblastic reticular cells to serve structural insights for splenic white pulps.

    • Hung-Wei Cheng
    • , Lucas Onder
    •  & Burkhard Ludewig
  • Article
    | Open Access

    Ageing causes an inability to replace damaged tissue. Here, the authors perform proteomics analyses of human haematopoietic stem cells and other cells in the bone marrow niche at different ages and show changes in central carbon metabolism, reduced bone marrow niche function, and enhanced myeloid differentiation.

    • Marco L. Hennrich
    • , Natalie Romanov
    •  & Anthony D. Ho
  • Article
    | Open Access

    Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow and gut microbiota. Here, the authors show that chronic hypoxia predisposes bone marrow stem cells to premature senescence, which may be due to gut dysbiosis and gut microbiota-derived d-galactose accumulation.

    • Junyue Xing
    • , Yongquan Ying
    •  & Hao Zhang
  • Article
    | Open Access

    The periosteum, a tissue lining the bone surface, and the bone marrow are known to contain bone-forming cells. Here the authors show that skeletal stem cells reside in the mouse periosteum, and that periosteal cells have common embryonic origins with bone marrow stromal/stem cells (BMSCs), but are better at bone repair and long-term integration than BMSCs.

    • Oriane Duchamp de Lageneste
    • , Anaïs Julien
    •  & Céline Colnot
  • Article
    | Open Access

    Heterotopic ossification (HO) is a painful disease of unknown etiology characterized by extraskeletal bone formation after injury. Here the authors show that TGF-β is increased in HO lesions, where it promotes the early stages of HO pathology, and demonstrate that TGF-β inhibition ameliorates HO in mice.

    • Xiao Wang
    • , Fengfeng Li
    •  & Xu Cao
  • Article
    | Open Access

    Mesenchymal stem cell (MSC) fate can be mechanically regulated by substrate stiffness but this is difficult to control in a 3D hydrogel. Here the authors identify miRNAs that change expression in response to substrate stiffness and RhoA signalling and show that they can bias MSC fate in a 3D soft hydrogel.

    • Jessica E. Frith
    • , Gina D. Kusuma
    •  & Justin J. Cooper-White
  • Article
    | Open Access

    Osteochondroprogenitors are essential cells for skeletal development and homeostasis. Here the authors show that the desumoylase SENP6 suppresses p53 activity by desumoylating and stabilising TRIM28, and that SENP6 ablation leads to skeletal abnormalities, senescence in osteochondroprogenitors and chondrocytes, and premature ageing.

    • Jianshuang Li
    • , Di Lu
    •  & Tao Yang
  • Article
    | Open Access

    Mesenchymal stem cells are essential for bone development, but it is unclear if their activity is maintained after late puberty, when bone growth decelerates. The authors show that during late puberty in mice, these cells undergo senescence under the epigenetic control of Ezh2.

    • Changjun Li
    • , Yu Chai
    •  & Mei Wan
  • Article
    | Open Access

    The stem cells that maintain and repair adult joint tissues in mammals, including articular cartilage, remain incompletely defined. Here the authors perform lineage tracing studies in adult mice and find an ontogenetically defined progenitor cell population that is functional in the synovial joint and distinct from previously reported mesenchymal stem cell populations.

    • Anke J. Roelofs
    • , Janja Zupan
    •  & Cosimo De Bari
  • Article
    | Open Access

    Bone marrow cells producing the intermediate filament nestin guide monocyte egress to the bloodstream in response to infection. Here, the authors show that nestin-producing stromal cells direct inflammatory cell migration in atherosclerosis, and that stromal Mcp1 is crucial in this process.

    • Raquel del Toro
    • , Raphael Chèvre
    •  & Simón Méndez-Ferrer
  • Article
    | Open Access

    Human mesenchymal stem cells (hMSC) expressing paracrine factors may enhance therapeutic benefits when transplanted. Here, the authors show that hMSCs stably expressing prostacyclin enhance host regeneration and muscle mass gain in a mouse hindlimb ischaemia model, mediated by the long noncoding RNA H19.

    • Yuxiao Deng
    • , Zhongwei Yang
    •  & Qi Liu
  • Article
    | Open Access

    TLR and IL-1R1 ligands are danger signals released following tissue injury and during the healing response. Here, the authors show that IL-1β signalling via IL-1R1/MyD88 inhibits the Akt/GSK-3β/β-catenin pathway in mesenchymal stem cells, which suppresses their mobilization, proliferation, and differentiation into osteoblasts, processes necessary for bone regeneration.

    • Mikaël M. Martino
    • , Kenta Maruyama
    •  & Shizuo Akira
  • Article
    | Open Access

    Regenerative tissue engineering with mesenchymal stem cells is hampered by bulk methods of assessing differentiation status and a general assumption that expression of individual markers of stem cell differentiation correlate with functional capacity. Here the authors debunk this assumption by applying single-cell techniques to disassociate aggrecan mRNA abundance and matrix deposition.

    • Allison J. Cote
    • , Claire M. McLeod
    •  & Robert L. Mauck
  • Article
    | Open Access

    The physiological role of crosstalk between mesenchymal stem cells (MSC) and macrophages is unclear. Here, Phinney et al. show that MSCs transfer mitochondria to macrophages under oxidative stress, and desensitize macrophages to mitochondria by using microvesicles to repress Toll receptor signalling.

    • Donald G. Phinney
    • , Michelangelo Di Giuseppe
    •  & Luis A. Ortiz
  • Article
    | Open Access

    Avoiding central cell necrosis at the centre of large engineered tissue constructs is an important issue forin vitrotissue engineering. Here, the authors demonstrate that this problem may be overcome by oxygenating human mesenchymal stem cells with artificial membrane-binding proteins.

    • James P. K. Armstrong
    • , Rameen Shakur
    •  & Anthony P. Hollander
  • Article |

    Central to the lineage commitment of multipotent mesenchymal stem cells is the nuclear receptor PPARγ, the master regulator of adipogenesis. Here the authors use a variety of structural approaches to rationally design PPARγ inverse agonist SR2595, and demonstrate its ability to promote osteogenesis.

    • David P. Marciano
    • , Dana S. Kuruvilla
    •  & Patrick R. Griffin
  • Article |

    Studying the effects of extracellular matrix stiffening has been impeded because mostin vitromodels are static. Here, dynamic hydrogels are developed that stiffen in the presence of cells and are used to investigate the short-term (minutes-to-hours) and long-term (days-to-weeks) cellular responses to dynamic stiffening.

    • Murat Guvendiren
    •  & Jason A. Burdick