Our goal was to assess the ability of native heart extracellular matrix (ECM) to direct cardiac differentiation of human embryonic stem cells (hESCs) in vitro. In order to probe the effects of cardiac matrix on hESC differentiation, a series of hydrogels was prepared from decellularized ECM from porcine hearts by mixing ECM and collagen type I at varying ratios. Maturation of cardiac function in embryoid bodies formed from hESCs was documented in terms of spontaneous contractile behavior and the mRNA and protein expression of cardiac markers. Hydrogel with high ECM content (75% ECM, 25% collagen, no supplemental soluble factors) increased the fraction of cells expressing cardiac marker troponin T, when compared with either hydrogel with low ECM content (25% ECM, 75% collagen, no supplemental soluble factors) or collagen hydrogel (100% collagen, with supplemental soluble factors). Furthermore, cardiac maturation was promoted in high-ECM content hydrogels, as evidenced by the striation patterns of cardiac troponin I and by upregulation of Cx43 gene. Consistently, high-ECM content hydrogels improved the contractile function of cardiac cells, as evidenced by increased numbers of contracting cells and increased contraction amplitudes. The ability of native ECM hydrogel to induce cardiac differentiation of hESCs without the addition of soluble factors makes it an attractive biomaterial system for basic studies of cardiac development and potentially for the delivery of therapeutic cells into the heart.

There is a growing interest in the pivotal role of exosomes in cancer and in their use as biomarkers. However, despite the importance of the microenvironment for cancer initiation and progression, monolayer cultures of tumor cells still represent the main in vitro source of exosomes. As a result, their environmental regulation remains largely unknown. Here, we report a three-dimensional tumor model for studying exosomes, using Ewing's sarcoma type 1 as a clinically relevant example. The bioengineered model was designed based on the hypothesis that the 3-dimensionality, composition and stiffness of the tumor matrix are the critical determinants of the size and cargo of exosomes released by the cancer cells. We analyzed the effects of the tumor microenvironment on exosomes, and the effects of exosomes on the non-cancer cells from the bone niche. Exosomes from the tissue-engineered tumor had similar size distribution as those in the patients' plasma, and were markedly smaller than those in monolayer cultures. Bioengineered tumors and the patients' plasma contained high levels of the Polycomb histone methyltransferase EZH2 mRNA relatively to their monolayer counterparts. Notably, EZH2 mRNA, a potential tumor biomarker detectable in blood plasma, could be transferred to the surrounding mesenchymal stem cells. This study provides the first evidence that an in vitro culture environment can recapitulate some properties of tumor exosomes.

The goal of this study was to develop a polymeric carrier for delivery of anti-tumor drugs and sustained release of these agents in order to optimize anti-tumor activity while minimizing systemic effects. We used oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels modified with small negatively charged molecules, sodium methacrylate (SMA), for delivery of doxorubicin (DOX). SMA at different concentrations was incorporated into the OPF hydrogel with a photo-crosslinking method. The resulting hydrogels exhibited sensitivity to the pH and ionic strength of the surrounding environment. Our results revealed that DOX was bound to the negatively charged hydrogel through electrostatic interaction and was released in a timely fashion with an ion exchange mechanism. Release kinetics of DOX was directly correlated to the concentration of SMA in the hydrogel formulations. Anti-tumor activity of the released DOX was assessed using a human osteosarcoma cell line. Our data revealed that DOX released from the modified, charged hydrogels remained biologically active and had the capability to kill cancer cells. In contrast, control groups of unmodified OPF hydrogels with or without DOX did not exhibit any cytotoxicity. This study demonstrates the feasibility of using SMA-modified OPF hydrogels as a potential carrier for chemotherapeutic drugs for cancer treatments.

The dominant roles of the tumor microenvironment in regulating tumor formation, progression, and metastasis have driven the application of tissue engineering strategies in cancer biology. Highly dynamic and reciprocal communication of tumor cells with their surroundings suggests that studying cancer in custom-designed biomaterial scaffolds may lead to novel therapeutic targets and therapeutic regimens more reliably than traditional monolayer tissue culture models. As tissue engineering becomes progressively more successful in recapitulating the native tumor environment, critical insights into mechanisms of tumor resistance may be elucidated, to impact clinical practice, drug development, and biological research. We review here the recent developments in the use of custom-designed biomaterial scaffolds for modeling human tumors.

Objective: Previous studies showed an inconsistent association of fruit and vegetable consumption with bone health. We assessed the associations in Chinese adolescents, young and postmenopausal women. Design: A cross-sectional study conducted in China during July 2009 to May 2010. Setting: Bone mineral density (BMD) and content (BMC) at the whole body, lumbar spine and left hip were measured with dual-energy X-ray absorptiometry. Dietary intakes were assessed using an FFQ. All these values were separately standardized into Z-scores in each population subgroup. Subjects: One hundred and ten boys and 112 girls (11-14 years), 371 young women (20-34 years, postpartum within 2 weeks) and 333 postmenopausal women (50-70 years). Results: After adjustment for potential covariates, analysis of covariance showed a significantly positive association between fruit intake and BMD and BMC in all participants combined (P-trend: , 0?001 to 0?002). BMD Z-score increased by 0?25 (or 2?1 % of the mean), 0?22 (3?5 %), 0?23 (3?0 %) and 0?25 (3?5 %), and BMC Z-score increased by 0?33 (5?7 %), 0?25 (5?8 %), 0?34 (5?9 %) and 0?29 (4?7 %), at the total body, lumbar spine, total hip and femoral neck in participants belonging to the top tertile compared with the bottom tertile of fruit intake (all P , 0?05), respectively. There was no significant association between vegetable intake and bone mass at all bone sites studied except for total body BMD (P 5 0?030). Relatively more pronounced effects were observed in boys and postmenopausal women. Conclusion: Our findings add to the existing evidence that fruits and vegetables may have a bone sparing effect.