LIM domain only 2 (LMO2) expression distinguishes T-lymphoblastic leukemia/lymphoma from indolent T-lymphoblastic proliferations.

Aims: An indolent T-lymphoblastic proliferation (iT-LBP) is a benign, reactive expansion of immature terminal deoxynucleotidyl transferase (TdT)-positive T cells found in extrathymic tissues. iT-LBP can be challenging to distinguish from malignant processes, specifically T-lymphoblastic lymphoma (T-LBL), given the overlapping clinical and histological features. Recently, it has been shown that LIM domain only 2 (LMO2) is overexpressed in T-LBL but not in reactive immature TdT+ T cells in the thymus.

Myeloid Cell Nuclear Differentiation Antigen (MNDA) Positivity in Primary Follicles: Potential Pitfall in the Differential Diagnosis With Marginal Zone Lymphoma.

Myeloid cell nuclear differentiation antigen (MNDA) is an immunohistochemical marker that is used to distinguish marginal zone lymphomas (MZLs) from other small B-cell lymphomas. An index case that showed MNDA staining in primary follicles prompted the current study to evaluate whether MNDA expression is widespread in primary follicles and to address whether it poses a potential diagnostic pitfall. Of the 15 cases with primary follicles identified by a search of the laboratory information system, 7 had positive MNDA staining.

Sudden Death of a Young Man by Acute Hemorrhagic Leukoencephalitis.

We report a case of acute hemorrhagic leukoencephalitis in an adult man with a prodrome of "feeling unwell" two days prior to this death. At autopsy, external examination revealed minor external injuries including contusions on the scalp and left thigh and abrasions on the forehead and right eyebrow. Gross examination of the brain after coronal sectioning revealed multiple petechial hemorrhages in the white matter in the cerebral hemispheres, corpus callosum, basal ganglia, brainstem, and cerebellum.

Tumor shrinkage associated with whole-mount histopathologic techniques in oral tongue carcinoma.

Shrinkage artifact of tumor tissue from histologic processing has not been rigorously quantified, particularly where the entire tumor is represented in a whole-mount specimen. Fourteen patients underwent partial-glossectomy for oral tongue carcinoma (OTC). Specimens were embedded into agar, cut into 3 mm blocks and photographed (macroscopic image), prior to histopathologic processing.

High-throughput combinatorial cell co-culture using microfluidics.

Co-culture strategies are foundational in cell biology. These systems, which serve as mimics of in vivo tissue niches, are typically poorly defined in terms of cell ratios, local cues and supportive cell-cell interactions. In the stem cell niche, the ability to screen cell-cell interactions and identify local supportive microenvironments has a broad range of applications in transplantation, tissue engineering and wound healing.

Enabling stem cell therapies through synthetic stem cell-niche engineering.

Enabling stem cell-targeted therapies requires an understanding of how to create local microenvironments (niches) that stimulate endogenous stem cells or serve as a platform to receive and guide the integration of transplanted stem cells and their derivatives. In vivo, the stem cell niche is a complex and dynamic unit. Although components of the in vivo niche continue to be described for many stem cell systems, how these components interact to modulate stem cell fate is only beginning to be understood.

Manipulation of signaling thresholds in "engineered stem cell niches" identifies design criteria for pluripotent stem cell screens.

In vivo, stem cell fate is regulated by local microenvironmental parameters. Governing parameters in this stem cell niche include soluble factors, extra-cellular matrix, and cell-cell interactions. The complexity of this in vivo niche limits analyses into how individual niche parameters regulate stem cell fate.

Micropatterning of human embryonic stem cells dissects the mesoderm and endoderm lineages.

Human pluripotent cells such as human embryonic stem cells (hESC) are a great potential source of cells for cell-based therapies; however, directing their differentiation into the desired cell types with high purity remains a challenge. The stem cell microenvironment plays a vital role in directing hESC fate and we have previously shown that manipulation of colony size in a serum- and cytokine-free environment controls self-renewal and differentiation toward the extraembryonic endoderm lineage. Here we show that, in the presence of bone morphogenetic protein 2 and activin A, control of colony size using a microcontact printing technology is able to direct hESC fate to either the mesoderm or the endoderm lineage.

Patterning mouse and human embryonic stem cells using micro-contact printing.

Local micro-environmental cues consisting of soluble cytokines, extra-cellular matrix (ECM), and cell-cell contacts are determining factors in stem cell fate. These extrinsic cues form a 'niche' that governs a stem cell's decision to either self-renew or differentiate into one or more cell types. Recently, it has been shown that micro-patterning stem cells in two- and three-dimensions can provide direct control over several parameters of the local micro-environment, including colony size, distance between colonies, ECM substrate, and homotypic or heterotypic cell-cell contact.

Generation of human embryonic stem cell-derived mesoderm and cardiac cells using size-specified aggregates in an oxygen-controlled bioreactor.

The ability to generate human pluripotent stem cell-derived cell types at sufficiently high numbers and in a reproducible manner is fundamental for clinical and biopharmaceutical applications. Current experimental methods for the differentiation of pluripotent cells such as human embryonic stem cells (hESC) rely on the generation of heterogeneous aggregates of cells, also called "embryoid bodies" (EBs), in small scale static culture. These protocols are typically (1) not scalable, (2) result in a wide range of EB sizes and (3) expose cells to fluctuations in physicochemical parameters.

Control of human embryonic stem cell colony and aggregate size heterogeneity influences differentiation trajectories.

To better understand endogenous parameters that influence pluripotent cell differentiation we used human embryonic stem cells (hESCs) as a model system. We demonstrate that differentiation trajectories in aggregate (embryoid body [EB])-induced differentiation, a common approach to mimic some of the spatial and temporal aspects of in vivo development, are affected by three factors: input hESC composition, input hESC colony size, and EB size. Using a microcontact printing approach, size-specified hESC colonies were formed by plating single-cell suspensions onto micropatterned (MP) extracellular matrix islands.

TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal.

Transforming growth factor-beta (TGFbeta) family members regulate many developmental and pathological events through Smad transcriptional modulators. How nuclear accumulation of Smad is coupled to the transcriptional machinery is poorly understood. Here we demonstrate that in response to TGFbeta stimulation the transcriptional regulator TAZ binds heteromeric Smad2/3-4 complexes and is recruited to TGFbeta response elements.

Niche-mediated control of human embryonic stem cell self-renewal and differentiation.

Complexity in the spatial organization of human embryonic stem cell (hESC) cultures creates heterogeneous microenvironments (niches) that influence hESC fate. This study demonstrates that the rate and trajectory of hESC differentiation can be controlled by engineering hESC niche properties. Niche size and composition regulate the balance between differentiation-inducing and -inhibiting factors.

Microfluidic production of biopolymer microcapsules with controlled morphology.

We report a microfluidic approach to generating capsules of biopolymer hydrogels. Droplets of an aqueous solution of a biopolymer were emulsified in an organic phase comprising a cross-linking agent. Polymer gelation was achieved in situ (on a microfluidic chip) by diffusion-controlled ionic cross-linking of the biopolymer, following the transfer of the cross-linking agent from the continuous phase to the droplets.

Development of a perfusion fed bioreactor for embryonic stem cell-derived cardiomyocyte generation: oxygen-mediated enhancement of cardiomyocyte output.

Cell transplantation is emerging as a promising new approach to replace scarred, nonfunctional myocardium in a diseased heart. At present, however, generating the numbers of donor cardiomyocytes required to develop and test animal models is a major limitation. Embryonic stem (ES) cells may be a promising source for therapeutic applications, potentially providing sufficient numbers of functionally relevant cells for transplantation into a variety of organs.