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Biomedical subjects

André A Neves

Publications and source records attributed to André A Neves.

5 recordsLinked to original sources

Assessing responses to cancer therapy using molecular imaging.

Tumor responses to therapy in the clinic are still evaluated primarily from non-invasive imaging measurements of reductions in tumor size. This approach, however, lacks sensitivity and can only give a delayed indication of a positive response to treatment. Major advances in our understanding of the molecular mechanisms responsible for cancer, combined with new targeted clinical imaging technologies designed to detect the molecular correlates of disease progression and response to treatment, are set to revolutionize our approach to the detection and treatment of the disease. We describe here the imaging technologies available to image tumor cell proliferation and migration, metabolism, receptor and gene expression, apoptosis and tumor angiogenesis and vascular function, and show how measurements of these parameters can be used to give early indications of positive responses to treatment or to detect drug resistance and/or disease recurrence. Special emphasis has been placed on those applications that are already used in the clinic and those that are likely to translate into clinical application in the near future or whose use in preclinical studies is likely to facilitate translation of new treatments into the clinic.

Antineoplastic Agents↗

Evaluation of engineered meniscal cartilage constructs based on different scaffold geometries using magnetic resonance imaging and spectroscopy.

Magnetic resonance imaging (MRI) and spectroscopy (MRS) were used to evaluate the properties different scaffold geometries for the production of bioartificial meniscal cartilage constructs. Engineered were generated in perfusion bioreactors from mature sheep meniscal fibrochondrocytes,scaffolds cut from a knitted polyethylene therephtalate (PET) fabric, with a distribution of fibers, 50 microm pores and a density of 45 mg/cm(3) (NF scaffolds), and from two versions of this fabric, which included larger pore sizes (1500 x 500 microm(2)) and densities of (sIV scaffolds) and 83 mg/cm(3) (sV scaffolds). MRI methods were used to determine the permeability the constructs to a low molecular weight MR contrast agent and to measure the macroscopic of medium through and around the constructs. These parameters were correlated with measurements of cell growth and cellular energetics. Cell-free sIV scaffolds were 2- and 5-more porous to flow than the empty sV and NF scaffolds, respectively. These scaffolds, after days of cell growth, were also more permeable to an MR contrast agent. sIV scaffolds yielded(n = 9) with higher cellularities (41 +/- 1%) compared with NF (32 +/- 1%, p < 0.0001) and sV (30 +/- 1%, p < 0.0001) and, when normalized to cell numbers, demonstrated proportionally levels of nucleoside triphosphates (NTP), indicating increased cell viability. Scaffold geometry a marked effect on the properties of engineered meniscal cartilage. MRI and MRS are powerful techniques that can be used to optimize the design of engineered meniscal cartilage and that could be used subsequently to evaluate clinical outcome postimplantation.

Animals↗

Influence of stirring-induced mixing on cell proliferation and extracellular matrix deposition in meniscal cartilage constructs based on polyethylene terephthalate scaffolds.

The response of engineered meniscal cartilage constructs to stirring-induced mixing in spinner flasks was investigated. Polyethylene terephthalate scaffolds were seeded with meniscal fibrochondrocytes from 6 month-old sheep and cultured under a variety of stirring regimes for 28 days. Stirring-induced mixing increased up to 7-fold the deposition of glucosaminoglycans and up to 3-fold the deposition of collagen, when compared to static cultures. High and medium intensity stirring induced rapid cell proliferation, with maximal cell densities achieved within the first seven days of cultivation. Under these conditions, collagen and glucosaminoglycan deposition occurred predominantly in association with cell proliferation, the specific deposition rate of these biopolymers decreasing markedly after 7 days of cultivation, when the cell number reached a plateau. Constructs exposed to the highest intensity stirring had the highest levels of collagen and glucosaminoglycans and a more homogeneous cell distribution. As the success of the integration at a repair site in the knee of a meniscal construct is likely to be dependent on the cellular activity of the construct, these studies suggest that cultivation of meniscal cartilage constructs, under these conditions, should not extend for more than 7 days.

Animals↗

Functional assessment of tissue-engineered meniscal cartilage by magnetic resonance imaging and spectroscopy.

A perfusion bioreactor system was used to grow bioartificial meniscal cartilage tissue in vitro. Magnetic resonance imaging and magnetic resonance spectroscopy methods were used to characterize the flow and perfusion profiles and the growth, distribution, and bioenergetics of the fibrochondrocytes in the resulting constructs. These measurements were correlated with each other and with subsequent histologic analysis. The study has demonstrated that these noninvasive magnetic resonance methods will be useful for designing bioreactor operation strategies and cell scaffolds that lead to the production of tissue-engineered meniscal cartilage constructs with properties resembling those of the native tissue.

Bioreactors↗