Tissue Engineering and Regenerative Medicine 2015: A Year in Review

Abstract

This may be the most exciting time ever for the field of tissue engineering and regenerative medicine (TERM). After decades of progress, it has matured, integrated, and diversified into entirely new areas, and it is starting to make the pivotal shift toward translation. The most exciting science and applications continue to emerge at the boundaries of disciplines, through increasingly effective interactions between stem cell biologists, bioengineers, clinicians, and the commercial sector. In this "Year in Review," we highlight some of the major advances reported over the last year (Summer 2014-Fall 2015). Using a methodology similar to that established in previous years, we identified four areas that generated major progress in the field: (i) pluripotent stem cells, (ii) microtissue platforms for drug testing and disease modeling, (iii) tissue models of cancer, and (iv) whole organ engineering. For each area, we used some of the most impactful articles to illustrate the important concepts and results that advanced the state of the art of TERM. We conclude with reflections on emerging areas and perspectives for future development in the field.

FIG. 1.

Overview of the key areas of tissue engineering and regenerative medicine research. Highlighted regions reflect topics covered in this review article.

FIG. 2.

Immunecompatibility of patient-specific induced pluripotent (iPS) cell derivatives. iPS derived cells have been considered as nonimmunogenic due to their autologous nature. By differentiating iPS cells into smooth muscle cells (SMCs) and retinal pigment epithelium (RPE), Zhao et al. demonstrate that depending on the iPS cell derivation protocol there is a greater or lesser immune cell infiltration when these cells are implanted into autologous humanized mouse models. These findings support the notion that there may be residual antigens on the cells following differentiation. Reproduced with permission from Zhao et al.

FIG. 3.

Engineered brain microtissues. (a) The brain contains multiple cortical layers of gray matter and white matter tracts. (b) The different layers of gray matter are recreated using six concentric rings of silk scaffold, which are each seeded with cortical neurons. The center of the disk contains collagen and serves as an axon reservoir. The complete, assembled scaffold is shown: (c) in original color (d) with each concentric ring stained with a different food color, and finally (e–g) with live cells stained with either DiI (red) or DiO (green) to demonstrate that the scaffold permits alternating cellular layers. Scale bar: 1 mm. Reproduced with permission from Tang-Schomer et al.

FIG. 4.

Engineering a bone cancer niche. Peripheral media channels enable cancer cells (CCs) to extravasate into the central tissue-mimicking gel comprised of endothelial cells (ECs), Mesenchymal stem cells (MSCs), and osteoblast-differentiated cells (OB). The ECs form vasculature within the gel whereas the MSCs and OBs serve to mimic a bone microenvironment. Migration toward this bone microenvironment was found to be greater than a muscle-mimicking environment, and the investigators implicate the role of the adenosine receptor in inhibiting CC migration. Reproduced with permission from Jeon et al.

FIG. 5.

Stepwise regeneration of decellularized rat forelimbs. (a) Schematic of perfusion bioreactor used for electrical stimulation of engineered muscle tissue. (A) Electrical field stimulation. (B) Medium perfusion. (b) Composite grafts are engineered in a stepwise fashion. Initially, acellular scaffolds are perfused with human umbilical vein endothelial cell (HUVECs) through the brachial artery. Subsequently myoblasts, HUVECs, and fibroblasts are introduced. Electrical stimulation is used to facilitate muscle maturation. Autologous skin is then grafted onto the construct to create a barrier against environmental stressors. (c) Photo of regenerated composite tissue (left) with a tissue cross-section (right). Scale bar: 5 mm. Reproduced with permission from Jank et al.