Designing stem cell niches for differentiation and self-renewal

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche. Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro. In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries

Cognition as Embodied Morphological Computation

Cognitive science is considered to be the study of mind (consciousness and thought) and intelligence in humans. Under such definition variety of unsolved/unsolvable problems appear. This article argues for a broad understanding of cognition based on empirical results from i.a. natural sciences, self-organization, artificial intelligence and artificial life, network science and neuroscience, that apart from the high level mental activities in humans, includes sub-symbolic and sub-conscious processes, such as emotions, recognizes cognition in other living beings as well as extended and distributed/social cognition. The new idea of cognition as complex multiscale phenomenon evolved in living organisms based on bodily structures that process information, linking cognitivists and EEEE (embodied, embedded, enactive, extended) cognition approaches with the idea of morphological computation (info-computational self-organisation) in cognizing agents, emerging in evolution through interactions of a (living/cognizing) agent with the environment

The living aortic valve: From molecules to function.

The aortic valve lies in a unique hemodynamic environment, one characterized by a range of stresses (shear stress, bending forces, loading forces and strain) that vary in intensity and direction throughout the cardiac cycle. Yet, despite its changing environment, the aortic valve opens and closes over 100,000 times a day and, in the majority of human beings, will function normally over a lifespan of 70-90 years. Until relatively recently heart valves were considered passive structures that play no active role in the functioning of a valve, or in the maintenance of its integrity and durability. However, through clinical experience and basic research the aortic valve can now be characterized as a living, dynamic organ with the capacity to adapt to its complex mechanical and biomechanical environment through active and passive communication between its constituent parts. The clinical relevance of a living valve substitute in patients requiring aortic valve replacement has been confirmed. This highlights the importance of using tissue engineering to develop heart valve substitutes containing living cells which have the ability to assume the complex functioning of the native valve

Multi-scale cellular engineering: From molecules to organ-on-a-chip.

Recent technological advances in cellular and molecular engineering have provided new insights into biology and enabled the design, manufacturing, and manipulation of complex living systems. Here, we summarize the state of advances at the molecular, cellular, and multi-cellular levels using experimental and computational tools. The areas of focus include intrinsically disordered proteins, synthetic proteins, spatiotemporally dynamic extracellular matrices, organ-on-a-chip approaches, and computational modeling, which all have tremendous potential for advancing fundamental and translational science. Perspectives on the current limitations and future directions are also described, with the goal of stimulating interest to overcome these hurdles using multi-disciplinary approaches

How to Color a French Flag--Biologically Inspired Algorithms for Scale-Invariant Patterning

In the French flag problem, initially uncolored cells on a grid must differentiate to become blue, white or red. The goal is for the cells to color the grid as a French flag, i.e., a three-colored triband, in a distributed manner. To solve a generalized version of the problem in a distributed computational setting, we consider two models: a biologically-inspired version that relies on morphogens (diffusing proteins acting as chemical signals) and a more abstract version based on reliable message passing between cellular agents. Much of developmental biology research has focused on concentration-based approaches using morphogens, since morphogen gradients are thought to be an underlying mechanism in tissue patterning. We show that both our model types easily achieve a French ribbon - a French flag in the 1D case. However, extending the ribbon to the 2D flag in the concentration model is somewhat difficult unless each agent has additional positional information. Assuming that cells are are identical, it is impossible to achieve a French flag or even a close approximation. In contrast, using a message-based approach in the 2D case only requires assuming that agents can be represented as constant size state machines. We hope that our insights may lay some groundwork for what kind of message passing abstractions or guarantees, if any, may be useful in analogy to cells communicating at long and short distances to solve patterning problems. In addition, we hope that our models and findings may be of interest in the design of nano-robots