Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects.

Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair.

Advancing immunomodulatory functions in mesenchymal stem/stromal cells through targeting the GATA6-mediated pathway.

Background Aims: The immunomodulatory capacity of mesenchymal stem/stromal cells (MSCs) is a key feature that makes them particularly valuable for regenerative medicine. However, this potential is affected by the chronological aging of the donors and the cell expansion procedures in culture. We have demonstrated that GATA binding protein 6 (GATA6) plays a pivotal role in the aging of MSCs and inhibiting GATA6 rejuvenates the characteristics of MSCs.

Diphenyl disulfide potentiates the apoptosis of breast cancer cells through Bax proteolytic activation with accompanying autophagy.

Breast cancer is a leading cause of cancer-related death worldwide, and chemoresistance often leads to poor patient outcomes. In this study, we investigated the anticancer activity of synthetic diphenyl disulfide (DPDS) in breast cancer cell lines. DPDS inhibited cellular proliferation and viability in a dose-dependent manner and reduced colony formation, an index of clonogenicity.

CTR9 drives osteochondral lineage differentiation of human mesenchymal stem cells via epigenetic regulation of BMP-2 signaling.

Cell fate determination of human mesenchymal stem/stromal cells (hMSCs) is precisely regulated by lineage-specific transcription factors and epigenetic enzymes. We found that CTR9, a key scaffold subunit of polymerase-associated factor complex (PAFc), selectively regulates hMSC differentiation to osteoblasts and chondrocytes, but not to adipocytes. An in vivo ectopic osteogenesis assay confirmed the essentiality of CTR9 in hMSC-derived bone formation.

Epigenetic regulation of BAF60A determines efficiency of miniature swine iPSC generation.

Miniature pigs are an ideal animal model for translational research to evaluate stem cell therapies and regenerative applications. While the derivation of induced pluripotent stem cells (iPSCs) from miniature pigs has been demonstrated, there is still a lack of a reliable method to generate and maintain miniature pig iPSCs. In this study, we derived iPSCs from fibroblasts of Wisconsin miniature swine (WMS), Yucatan miniature swine (YMS), and Göttingen minipigs (GM) using our culture medium.

Reprogrammed Synovial Fluid-Derived Mesenchymal Stem/Stromal Cells Acquire Enhanced Therapeutic Potential for Articular Cartilage Repair.

Objectives: Functions of mesenchymal stem/stromal cells (MSCs) are affected by patient-dependent factors such as age and health condition. To tackle this problem, we used the cellular reprogramming technique to epigenetically alter human MSCs derived from the synovial fluid of joints with osteoarthritis (OA) to explore the potential of reprogrammed MSCs for repairing articular cartilage.

Materials And Methods: MSCs isolated from the synovial fluid of three patients' OA knees (Pa-MSCs) were reprogrammed through overexpression of pluripotency factors and then induced for differentiation to establish reprogrammed MSC (Re-MSC) lines.

Comparative evaluation of isogenic mesodermal and ectomesodermal chondrocytes from human iPSCs for cartilage regeneration.

Generating phenotypic chondrocytes from pluripotent stem cells is of great interest in the field of cartilage regeneration. In this study, we differentiated human induced pluripotent stem cells into the mesodermal and ectomesodermal lineages to prepare isogenic mesodermal cell-derived chondrocytes (MC-Chs) and neural crest cell-derived chondrocytes (NCC-Chs), respectively, for comparative evaluation. Our results showed that both MC-Chs and NCC-Chs expressed hyaline cartilage-associated markers and were capable of generating hyaline cartilage-like tissue ectopically and at joint defects.

Bi-component T2 mapping correlates with articular cartilage material properties.

Non-invasive estimation of cartilage material properties is useful for understanding cartilage health and creating subject-specific computational models. Bi-component T2 mapping measured using Multi-Component Driven Equilibrium Single Shot Observation of T and T (mcDESPOT) is sensitive for detecting cartilage degeneration within the human knee joint, but has not been correlated with cartilage composition and mechanical properties. Therefore, the purpose of this study was to investigate the relationship between bi-component T parameters measured using mcDESPOT at 3.

Collagen and chondroitin sulfate functionalized bioinspired fibers for tendon tissue engineering application.

Functional tendon tissue engineering depends on harnessing the biochemical and biophysical cues of the native tendon extracellular matrix. In this study, we fabricated highly-aligned poly(L-lactic acid) (PLLA) fibers with surfaces decorated by two of the crucial tendon ECM components, type 1 collagen (COL1) and chondroitin sulfate (CS), through a coaxial stable jet electrospinning approach. Effects of the biomimetic COL1-CS (shell)/PLLA (core) fibers on the tenogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro were investigated.

Endothelin-1 reduces catabolic activity of human mesenchymal stem/stromal cells during chondro- and osteo-lineage differentiation.

Human mesenchymal stem/stromal cells (hMSCs) reside in a vascularized microenvironment and experience a host of blood vessel secretions, including endothelin-1 (ET1). Previously, our group has demonstrated improved induction of osteogenesis and chondrogenesis in hMSCs through an ET1-induced increase in production of anabolic factors. The current study explores effects of ET1 on catabolic factors secreted by hMSCs during chondrogenesis and osteogenesis.

Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow-Derived Mesenchymal Stem Cells.

Background: Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM.

Purpose: To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model.

Study Design: Controlled laboratory study.

Emerging opportunities for induced pluripotent stem cells in orthopaedics.

Unlabelled: The discovery of induced pluripotent stem cells (iPSCs) has revolutionized biomedicine. Although the potential of iPSCs for tissue regeneration, disease modeling and drug screening has been largely recognized, findings of iPSC research to date are mostly focused on neurology, cardiology and haematology. For orthopaedics, growing interest in the unique cell type has prompted more researchers to get involved in iPSC research.

Human pluripotent stem cell-derived brain pericyte-like cells induce blood-brain barrier properties.

Brain pericytes play important roles in the formation and maintenance of the neurovascular unit (NVU), and their dysfunction has been implicated in central nervous system disorders. While human pluripotent stem cells (hPSCs) have been used to model other NVU cell types, including brain microvascular endothelial cells (BMECs), astrocytes, and neurons, hPSC-derived brain pericyte-like cells have not been integrated into these models. In this study, we generated neural crest stem cells (NCSCs), the embryonic precursor to forebrain pericytes, from hPSCs and subsequently differentiated NCSCs to brain pericyte-like cells.

Bone Morphogenetic Protein-6 Attenuates Type 1 Diabetes Mellitus-Associated Bone Loss.

Patients with type 1 diabetes mellitus (T1DM) often suffer from osteopenia or osteoporosis. Although most agree that T1DM-induced hyperglycemia is a risk factor for progressive bone loss, the mechanisms for the link between T1DM and bone loss still remain elusive. In this study, we found that bone marrow-derived mesenchymal stem cells (BMSCs) isolated from T1DM donors were less inducible for osteogenesis than those from non-T1DM donors and further identified a mechanism involving bone morphogenetic protein-6 (BMP6) that was produced significantly less in BMSCs derived from T1DM donors than that in control cells.

Emergence of topological phases by stacking of two-dimensional lattices with nonsymmorphic symmetry.

Topological semimetals have a variety of phases, whose Fermi surfaces can be nodal points, nodal lines and nodal loops. Here we construct four classes of 3D minimal models via vertically stacking a 2D nonsymmorphic lattice with and without breaking crystalline symmetries. As a result, four distinct topological phases can be generated in our minimal model, such as Dirac nodal line semimetals, Weyl nodal line semimetals, unconventional Weyl semimetals with topological charge [Formula: see text], and weak topological insulators.

Endothelin-1 differentially directs lineage specification of adipose- and bone marrow-derived mesenchymal stem cells.

Blood vessels composed of endothelial cells (ECs) contact with mesenchymal stem cells (MSCs) in different tissues, suggesting possible interaction between these 2 types of cells. We hypothesized that endothelin-1 (ET1), a secreted paracrine factor of ECs, can differentially direct the lineages of adipose-derived stem cells (ASCs) and bone marrow-derived MSCs (BMSCs). Predifferentiated ASCs and BMSCs were treated with ET1 for 2 cell passages and then induced for multilineage differentiation.

Endogenous biological factors modulated by substrate stiffness regulate endothelial differentiation of mesenchymal stem cells.

During the process of tissue regeneration facilitated by stem cells, physical properties of a scaffold affect behavior and activities of the cell. To enhance differentiation of human mesenchymal stem cells (MSCs) into endothelial-like cells (ELCs), we used electrospun fibrous substrates with different stiffness to enhance the differentiation. A simple method of annealing with different lengths of treatment time was employed to modulate stiffness of electrospun fibrous substrates without changing their chemistry.

Strategies to retain properties of bone marrow-derived mesenchymal stem cells ex vivo.

Mesenchymal stem cells (MSCs) have been extensively used for cell therapies and tissue engineering. The current MSC strategy requires a large quantity of cells for such applications, which can be achieved through cell expansion in culture. In the body, stem cell fate is largely determined by their microenvironment, known as the niche.

Mechano-Signal Transduction in Mesenchymal Stem Cells Induces Prosaposin Secretion to Drive the Proliferation of Breast Cancer Cells.

In response to chemical stimuli from cancer cells, mesenchymal stem cells (MSC) can differentiate into cancer-associated fibroblasts (CAF) and promote tumor progression. How mechanical stimuli such as stiffness of the extracellular matrix (ECM) contribute to MSC phenotype in cancer remains poorly understood. Here, we show that ECM stiffness leads to mechano-signal transduction in MSC, which promotes mammary tumor growth in part through secretion of the signaling protein prosaposin.

Identification of Bone Marrow-Derived Soluble Factors Regulating Human Mesenchymal Stem Cells for Bone Regeneration.

Maintaining properties of human bone marrow-derived mesenchymal stem cells (BMSCs) in culture for regenerative applications remains a great challenge. An emerging approach of constructing a culture environment mimicking the bone marrow niche to regulate BMSC activities has been developed. In this study, we have demonstrated a systematic approach to identify soluble factors of interest extracted from human bone marrow and used them in BMSC culture for tissue regeneration.