Development of a Three-Dimensional Bioengineering Technology to Generate Lung Tissue for Personalized Disease Modeling.

Stem cell technologies, especially patient-specific, induced stem cell pluripotency and directed differentiation, hold great promise for changing the landscape of medical therapies. Proper exploitation of these methods may lead to personalized organ transplants, but to regenerate organs, it is necessary to develop methods for assembling differentiated cells into functional, organ-level tissues. The generation of three-dimensional human tissue models also holds potential for medical advances in disease modeling, as full organ functionality may not be necessary to recapitulate disease pathophysiology.

Protein Adsorption Alters Hydrophobic Surfaces Used for Suspension Culture of Pluripotent Stem Cells.

This Letter examines the physical and chemical changes that occur at the interface of methyl-terminated alkanethiol self-assembled monolayers (SAMs) after exposure to cell culture media used to derive embryoid bodies (EBs) from pluripotent stem cells. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy analysis of the SAMs indicates that protein components within the EB cell culture medium preferentially adsorb at the hydrophobic interface. In addition, we examined the adsorption process using surface plasmon resonance and atomic force microscopy.

Ensemble multivariate analysis to improve identification of articular cartilage disease in noisy Raman spectra.

The development of new methods for the early diagnosis of cartilage disease could offer significant improvement in patient care. Raman spectroscopy is an emerging biomedical technology with unique potential to recognize disease tissues, though difficulty in obtaining the samples needed to train a diagnostic and excessive signal noise could slow its development into a clinical tool. In the current report we detail the use of principal component analysis--linear discriminant analysis (PCA-LDA) on spectra from pairs of materials modeling cartilage disease to create multiple spectral scoring metrics, which could limit the reliance on primary training data for identifying disease in low signal-to-noise-ratio (SNR) Raman spectra.

Chemoselective immobilization of proteins by microcontact printing and bio-orthogonal click reactions.

Herein, a combination of microcontact printing of functionalized alkanethiols and site-specific modification of proteins is utilized to chemoselectively immobilize proteins onto gold surfaces, either by oxime- or copper-catalyzed alkyne-azide click chemistry. Two molecules capable of click reactions were synthesized, an aminooxy-functionalized alkanethiol and an azide-functionalized alkanethiol, and self-assembled monolayer (SAM) formation on gold was confirmed by IR spectroscopy. The alkanethiols were then individually patterned onto gold surfaces by microcontact printing.

Lysophosphatidic acid mediates myeloid differentiation within the human bone marrow microenvironment.

Lysophosphatidic acid (LPA) is a pleiotropic phospholipid present in the blood and certain tissues at high concentrations; its diverse effects are mediated through differential, tissue specific expression of LPA receptors. Our goal was to determine if LPA exerts lineage-specific effects during normal human hematopoiesis. In vitro stimulation of CD34+ human hematopoietic progenitors by LPA induced myeloid differentiation but had no effect on lymphoid differentiation.

A spatially and chemically defined platform for the uniform growth of human pluripotent stem cells.

We report the design of a chemically defined platform engineered for the culture of human pluripotent stem cells (hPSCs) that supports the long-term maintenance of self-renewing hPSC populations in a more uniform manner than standard culture systems. Microcontact printing (μCP) of alkanethiol self-assembled monolayers (SAMs) was used to spatially direct hPSC adherence. This technique not only establishes control over hPSC colony size and shape but also preserves genetic stability and provides unprecedented uniformity in the pluripotency of hPSC populations that is quantitatively assessed in the present study.