The Lactate Receptor GPR81 is a Mechanism of Leukemia-Associated Macrophage Polarization in the Bone Marrow Microenvironment.

Interactions between acute myeloid leukemia (AML) and the bone marrow microenvironment (BMME) are critical to leukemia progression and chemoresistance. Altered metabolite levels in the tumor microenvironment contribute to immunosuppression in solid tumors, while this has not been studied yet in the leukemic BMME. Metabolomics of AML patient bone marrow serum detected elevated metabolites, including lactate, compared to age- and sex-matched controls.

Myelodysplastic syndromes disable human CD271+VCAM1+CD146+ niches supporting normal hematopoietic stem/progenitor cells.

Mesenchymal stem/stromal cells (MSCs) within the bone marrow microenvironment (BMME) support normal hematopoietic stem and progenitor cells (HSPCs). However, the heterogeneity of human MSCs has limited the understanding of their contribution to clonal dynamics and evolution to myelodysplastic syndromes (MDS). We combined three MSC cell surface markers, CD271, VCAM-1 (Vascular Cell Adhesion Molecule-1) and CD146, to isolate distinct subsets of human MSCs from bone marrow aspirates of healthy controls (Control BM).

The Potential Role of 3D In Vitro Acute Myeloid Leukemia Culture Models in Understanding Drug Resistance in Leukemia Stem Cells.

The complexity of the bone marrow (BM) microenvironment makes studying hematological malignancies in vitro a challenging task. Three-dimensional cell cultures are being actively studied, particularly due to their ability to serve as a bridge of the gap between 2D cultures and animal models. The role of 3D in vitro models in studying the mechanisms of chemotherapeutic resistance and leukemia stem cells (LSCs) in acute myeloid leukemia (AML) is not well-reviewed.

Bone Marrow Microenvironment-On-Chip for Culture of Functional Hematopoietic Stem Cells.

Hematopoiesis takes place in the bone marrow and is supported by a complex cellular and molecular network in the bone marrow microenvironment. Commonly used models of the human bone marrow microenvironment include murine models and two-dimensional and three-dimensional tissue cultures. While these model systems have led to critical advances in the field, they fail to recapitulate many aspects of the human bone marrow.

Coherent response of the electronic system driven by non-interfering laser pulses.

The strength of light-matter interaction in condensed matter is fundamentally linked to the orientation and oscillation strength of the materials' optical transition dipoles. Structurally anisotropic materials, e.g.

Nanoparticle-Mediated Delivery of Micheliolide Analogs to Eliminate Leukemic Stem Cells in the Bone Marrow.

Micheliolide (MCL) is a naturally occurring sesquiterpene lactone that selectively targets leukemic stem cells (LSCs), which persist after conventional chemotherapy for myeloid leukemias, leading to disease relapse. To overcome modest MCL cytotoxicity, analogs with ≈two-threefold greater cytotoxicity against LSCs are synthesized via late-stage chemoenzymatic C-H functionalization. To enhance bone marrow delivery, MCL analogs are entrapped within bone-targeted polymeric nanoparticles (NPs).

Energy and Momentum Distribution of Surface Plasmon-Induced Hot Carriers Isolated Spatiotemporal Separation.

Understanding the differences between photon-induced and plasmon-induced hot electrons is essential for the construction of devices for plasmonic energy conversion. The mechanism of the plasmonic enhancement in photochemistry, photocatalysis, and light-harvesting and especially the role of hot carriers is still heavily discussed. The question remains, if plasmon-induced and photon-induced hot carriers are fundamentally different or if plasmonic enhancement is only an effect of field concentration producing these carriers in greater numbers.

From the niche to malignant hematopoiesis and back: reciprocal interactions between leukemia and the bone marrow microenvironment.

The bone marrow microenvironment (BMME) regulates hematopoiesis through a complex network of cellular and molecular components. Hematologic malignancies reside within, and extensively interact with, the same BMME. These interactions consequently alter both malignant and benign hematopoiesis in multiple ways, and can encompass initiation of malignancy, support of malignant progression, resistance to chemotherapy, and loss of normal hematopoiesis.

Reduction of leukemic burden via bone-targeted nanoparticle delivery of an inhibitor of C-chemokine (C-C motif) ligand 3 (CCL3) signaling.

Leukemias are challenging diseases to treat due, in part, to interactions between leukemia cells and the bone marrow microenvironment (BMME) that contribute significantly to disease progression. Studies have shown that leukemic cells secrete C-chemokine (C-C motif) ligand 3 (CCL3), to disrupt the BMME resulting in loss of hematopoiesis and support of leukemic cell survival and proliferation. In this study, a murine model of blast crisis chronic myelogenous leukemia (bcCML) that expresses the translocation products BCR/ABL and Nup98/HoxA9 was used to determine the role of CCL3 in BMME regulation.

Hematopoietic Stem Cell Cultures and Assays.

The adult hematopoietic system is repopulated in its entirety from a rare cell type known as hematopoietic stem cells (HSCs) that reside in the marrow space throughout the skeletal system. Here we describe the isolation and identification of HSCs both phenotypically and functionally.

Aged marrow macrophages expand platelet-biased hematopoietic stem cells via Interleukin1B.

The bone marrow microenvironment (BMME) contributes to the regulation of hematopoietic stem cell (HSC) function, though its role in age-associated lineage skewing is poorly understood. Here we show that dysfunction of aged marrow macrophages (Mφs) directs HSC platelet-bias. Mφs from the marrow of aged mice and humans exhibited an activated phenotype, with increased expression of inflammatory signals.

EVI1 overexpression reprograms hematopoiesis via upregulation of Spi1 transcription.

Inv(3q26) and t(3:3)(q21;q26) are specific to poor-prognosis myeloid malignancies, and result in marked overexpression of EVI1, a zinc-finger transcription factor and myeloid-specific oncoprotein. Despite extensive study, the mechanism by which EVI1 contributes to myeloid malignancy remains unclear. Here we describe a new mouse model that mimics the transcriptional effects of 3q26 rearrangement.

The Chemokine CCL3 Regulates Myeloid Differentiation and Hematopoietic Stem Cell Numbers.

The chemokine CCL3 is frequently overexpressed in malignancies and overexpression leads to microenvironmental dysfunction. In murine models of chronic myelogenous leukemia (CML), CCL3 is critical for the maintenance of a leukemia stem cell population, and leukemia progression. With CCL3 implicated as a potentially viable therapeutic target, it is important to carefully characterize its role in normal hematopoietic homeostasis.

The hematopoietic stem cell niche: What's so special about bone?

Hematopoietic stem cells (HSCs) require a supportive microenvironment to regulate their function and produce sufficient hematopoietic cells over the lifetime of an individual. With the exception of fish, all vertebrates, including mammals, maintain HSCs in a complex niche within the bone marrow. Several bone specific cellular populations have been implicated as components of the HSC niche and are part of a complex network that regulates HSC functions.

Robotic ultrasound-guided facet joint insertion.

Purpose: Facet joint insertion is a common treatment of chronic pain in the back and spine. This procedure is often performed under fluoroscopic guidance, where the staff's repetitive radiation exposure remains an unsolved problem. Robotic ultrasound (rUS) has the potential to reduce or even eliminate the use of radiation by using ultrasound with a robotic-guided needle insertion.

Anticancer activity profiling of parthenolide analogs generated via P450-mediated chemoenzymatic synthesis.

The plant-derived sesquiterpene lactone parthenolide (PTL) was recently found to possess promising anticancer activity but elaboration of this natural product scaffold for optimization of its pharmacological properties has proven challenging via available chemical methods. In this work, P450-catalyzed C-H hydroxylation of positions C9 and C14 in PTL was coupled to carbamoylation chemistry to yield a panel of novel carbamate-based PTL analogs ('parthenologs'). These compounds, along with a series of other C9- and C14-functionalized parthenologs obtained via O-H acylation, alkylation, and metal-catalyzed carbene insertion, were profiled for their cytotoxicity against a diverse panel of human cancer cell lines.

Acoustic window planning for ultrasound acquisition.

Unlabelled: Autonomous robotic ultrasound has recently gained considerable interest, especially for collaborative applications. Existing methods for acquisition trajectory planning are solely based on geometrical considerations, such as the pose of the transducer with respect to the patient surface.

Purpose: This work aims at establishing acoustic window planning to enable autonomous ultrasound acquisitions of anatomies with restricted acoustic windows, such as the liver or the heart.

The Notch Ligand Jagged1 Regulates the Osteoblastic Lineage by Maintaining the Osteoprogenitor Pool.

Notch signaling is critical for osteoblastic differentiation; however, the specific contribution of individual Notch ligands is unknown. Parathyroid hormone (PTH) regulates the Notch ligand Jagged1 in osteoblastic cells. To determine if osteolineage Jagged1 contributes to bone homeostasis, selective deletion of Jagged1 in osteolineage cells was achieved through the presence of Prx1 promoter-driven Cre recombinase expression, targeting mesenchymal stem cells (MSCs) and their progeny (PJag1 mice).

3D ultrasound registration-based visual servoing for neurosurgical navigation.

Purpose: We present a fully image-based visual servoing framework for neurosurgical navigation and needle guidance. The proposed servo-control scheme allows for compensation of target anatomy movements, maintaining high navigational accuracy over time, and automatic needle guide alignment for accurate manual insertions.

Method: Our system comprises a motorized 3D ultrasound (US) transducer mounted on a robotic arm and equipped with a needle guide.

Flexible mini gamma camera reconstructions of extended sources using step and shoot and list mode.

Purpose: Hand- and robot-guided mini gamma cameras have been introduced for the acquisition of single-photon emission computed tomography (SPECT) images. Less cumbersome than whole-body scanners, they allow for a fast acquisition of the radioactivity distribution, for example, to differentiate cancerous from hormonally hyperactive lesions inside the thyroid. This work compares acquisition protocols and reconstruction algorithms in an attempt to identify the most suitable approach for fast acquisition and efficient image reconstruction, suitable for localization of extended sources, such as lesions inside the thyroid.

Towards MRI-Based Autonomous Robotic US Acquisitions: A First Feasibility Study.

Robotic ultrasound has the potential to assist and guide physicians during interventions. In this work, we present a set of methods and a workflow to enable autonomous MRI-guided ultrasound acquisitions. Our approach uses a structured-light 3D scanner for patient-to-robot and image-to-patient calibration, which in turn is used to plan 3D ultrasound trajectories.

Multimodal US-gamma imaging using collaborative robotics for cancer staging biopsies.

Purpose: The staging of female breast cancer requires detailed information about the level of cancer spread through the lymphatic system. Common practice to obtain this information for patients with early-stage cancer is sentinel lymph node (SLN) biopsy, where LNs are radioactively identified for surgical removal and subsequent histological analysis. Punch needle biopsy is a less invasive approach but suffers from the lack of combined anatomical and nuclear information.

Personalized, relevance-based Multimodal Robotic Imaging and augmented reality for Computer Assisted Interventions.

In the last decade, many researchers in medical image computing and computer assisted interventions across the world focused on the development of the Virtual Physiological Human (VPH), aiming at changing the practice of medicine from classification and treatment of diseases to that of modeling and treating patients. These projects resulted in major advancements in segmentation, registration, morphological, physiological and biomechanical modeling based on state of art medical imaging as well as other sensory data. However, a major issue which has not yet come into the focus is personalizing intra-operative imaging, allowing for optimal treatment.