Mastering translational medicine: interdisciplinary education for a new generation.

Graduate-level education in translational medicine will require more than just scientific research.

Biophysical regulation of histone acetylation in mesenchymal stem cells.

Histone deacetylation and acetylation are catalyzed by histone deacetylase (HDAC) and histone acetyltransferase, respectively, which play important roles in the regulation of chromatin remodeling, gene expression, and cell functions. However, whether and how biophysical cues modulate HDAC activity and histone acetylation is not well understood. Here, we tested the hypothesis that microtopographic patterning and mechanical strain on the substrate regulate nuclear shape, HDAC activity, and histone acetylation.

Engineering bi-layer nanofibrous conduits for peripheral nerve regeneration.

Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam.

Proteomic identification of biomarkers of vascular injury.

Predictive biomarkers may be beneficial for detecting, diagnosing, and assessing the risk of restenosis and vascular injury. We utilized proteomic profiling to identify protein markers in the blood following vascular injury, and corroborated the differential protein expression with immunological approaches. Rats underwent carotid artery injury, and plasma was collected after 2 or 5 weeks.

Dura mater regeneration with a novel synthetic, bilayered nanofibrous dural substitute: an experimental study.

Aim: To create a synthetic nanofibrous dural substitute that overcomes the limitations of current devices by enhancing dural healing via biomimetic nanoscale architecture and supporting both onlaid and sutured implantation.

Materials & Methods: A custom electrospinning process was used to create a bilayer dural substitute having aligned nanofibers on one side and random nanofibers on the other. Nanoscale architecture was verified using microscopy and macroscale mechanical properties were investigated using tensile testing.

Transforming growth factor-beta and notch signaling mediate stem cell differentiation into smooth muscle cells.

The differentiation of stem cells into smooth muscle cells (SMCs) plays an important role in vascular development and remodeling. In addition, stem cells represent a potential source of SMCs for regenerative medicine applications such as constructing vascular grafts. Previous studies have suggested that various biochemical factors, including transforming growth factor-beta (TGF-beta) and the Notch pathway, may play important roles in vascular differentiation.

The effect of fiber alignment and heparin coating on cell infiltration into nanofibrous PLLA scaffolds.

Biodegradable nanofibers simulate the fibril structure of natural extracellular matrix, and provide a cell-friendly microenvironment for tissue regeneration. However, the effects of nanofiber organization and immobilized biochemical factors on cell infiltration into three-dimensional scaffolds are not well understood. For example, cell infiltration into an electrospun nanofibrous matrix is often limited due to relatively small pore size between the fibers.

Proteomic Profiling of Mesenchymal Stem Cell Responses to Mechanical Strain and TGF-beta1.

Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells (SMCs) for constructing tissue-engineered vascular grafts. However, the details of how specific combinations of vascular microenvironmental factors regulate MSCs are not well understood. Previous studies have suggested that both mechanical stimulation with uniaxial cyclic strain and chemical stimulation with transforming growth factor-beta1 (TGF-beta1) can induce smooth muscle markers in MSCs.

Differential effects of x-rays and high-energy 56Fe ions on human mesenchymal stem cells.

Purpose: Stem cells hold great potential for regenerative medicine, but they have also been implicated in cancer and aging. How different kinds of ionizing radiation affect stem cell biology remains unexplored. This study was designed to compare the biological effects of X-rays and of high-linear energy transfer (LET) (56)Fe ions on human mesenchymal stem cells (hMSC).

Mechanical stimulation of stem cells using cyclic uniaxial strain.

The role of mechanical forces in the development and maintenance of biological tissues is well documented, including several mechanically regulated phenomena such as bone remodeling, muscular hypertrophy, and smooth muscle cell plasticity. However, the forces involved are often extremely complex and difficult to monitor and control in vivo. To better investigate the effects of mechanical forces on cells, we have developed an in vitro method for applying uniaxial cyclic tensile strain to adherent cells cultured on elastic membranes.

Mechanobiology of mesenchymal stem cells and their use in cardiovascular repair.

Mesenchymal stem cells (MSCs) derived from bone marrow have shown great promise in tissue repair. While these cells induce little immune response, they show marked self-renewal properties and can differentiate into many cell types. Recent evidence shows that mechanical factors such as fluid shear stress, mechanical strain and the rigidity of extracellular matrix can regulate the proliferation and differentiation of MSCs through various signaling pathways.

Bioactive nanofibers: synergistic effects of nanotopography and chemical signaling on cell guidance.

Biodegradable nanofibers have tremendous potential for tissue repair. However, the combined effects of nanofiber organization and immobilized bioactive factors on cell guidance are not well understood. In this study, we developed aligned and bioactive nanofibrous scaffolds by immobilizing extracellular matrix protein and growth factor onto nanofibers, which simulated the physical and biochemical properties of native matrix fibrils.

Anisotropic mechanosensing by mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are a potential source for the construction of tissue-engineered vascular grafts. However, how vascular mechanical forces regulate the genetic reprogramming in MSCs is not well understood. Mechanical strain in the vascular wall is anisotropic and mainly in the circumferential direction.

Regulation of vascular smooth muscle cells and mesenchymal stem cells by mechanical strain.

Vascular smooth muscle cells (SMCs) populate in the media of the blood vessel, and play an important role in the control of vasoactivity and the remodeling of the vessel wall. Blood vessels are constantly subjected to hemodynamic stresses, and the pulsatile nature of the blood flow results in a cyclic mechanical strain in the vessel walls. Accumulating evidence in the past two decades indicates that mechanical strain regulates vascular SMC phenotype, function and matrix remodeling.

Designation of the TARP syndrome and linkage to Xp11.23-q13.3 without samples from affected patients.

The Robin sequence is a well-known cause of cleft palate and can be sporadic or familial, isolated or syndromic. We present a four-generation family with a lethal disorder inherited in an X-linked recessive pattern that includes Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistence of the left superior vena cava. We have designated this disorder "TARP" syndrome.