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In the past several years, substantial progress has been made in identifying and addressing challenges in commercial and medical utilization of stem cells for drug evaluation and screening, development and disease modeling, and implementation of cell-based therapies. These advances have been the result of interactions between the stem cell biology and the bioengineering communities. The goal of this Special Issue of Biotechnology Journal dedicated to stem cell engineering is to explore the current state-of-the-art, and ponders future directions in bridging biology and engineering for the purpose of enabling translation of stem cell technologies to the marketplace and clinic.

This Special Issue of BTJ on stem cell engineering explores the current state-of-the-art and ponders future directions in bridging biology and engineering to bring stem cell technologies to the clinic.

Important advances have been made in developing culture systems for derivation, expansion, and differentiation of many different stem cell types, but significant hurdles remain. Currently, these hurdles include a lack of physiologically relevant microenvironments to provide defined cues to cells in the appropriate spatial and temporal context; robust scaling of culture and differentiation systems to provide sufficient numbers and quality of cells for biomedical applications; standardizing molecular and phenotypic metrics to characterize and define stem cells and their progeny; and monitoring, understanding, and regulating heterogeneous populations of cells in culture. In this issue, Simoes et al. [1] describe isolation and expansion of mesenchymal stem cells (MSCs) from umbilical cord matrix under defined serum-/xeno-free conditions. This study advances cell processing toward producing safer stem cell populations for cellular therapies. Rafiq et al. [2] explain the effects of oxygen and media exchange on human MSC metabolism and expansion. This article illustrates how laboratory experiments can guide development of scalable stem cell expansion systems. Choi and Murphy [3] report the development of an experimental platform to facilitate screening of the effects of inorganic biomaterial coatings on MSCs and identified a novel role of mineral coating morphology on hMSC expansion and osteogenic differentiation. Vincent et al. [4] report that substrate mechanics regulate MSC migration, suggesting that the mechanical microenvironment may regulate contributions of MSCs to development and regeneration in vivo.

Translating advances in stem cell science and engineering to the clinic will require expertise in tissue engineering, including designing and fabricating microenvironments to support cells, guide their function, and facilitate delivery.

The emerging technology of reprogramming cells from one state to another offers tremendous potential for generating stem and somatic cells with a desired genetic background, including patient-specific cells for transplantation and disease cells for modeling and drug discovery. In addition to engineering reprogramming tools, challenges in reprogramming include defining cell states, both molecularly and phenotypically, and identifying transitions between states. Along these lines, Gibson and Gersbach [5] describe the technologies for single cell analysis that will be important for characterizing cell heterogeneity and its effects on stem cell state transitions. Mooney et al. [6] review how cancer biology has provided insight into mechanistic regulation of stem cell fate decisions and how stem cell interactions with cancer cells may advance cancer therapies. Tiruthani et al. [7] describe recent advances in differentiating human embryonic stem cells to trophoblast-like cells, providing a window into the earliest stages of human development.

Transitioning from 2D to 3D environments represents a crucial step in translating laboratory findings into the clinic.

Translating advances in stem cell science and engineering to the clinic will require expertise in tissue engineering, including designing and fabricating microenvironments to support cells, guide their function, and facilitate delivery. Transitioning from 2D to 3D environments represents a crucial step in translating laboratory findings into the clinic. Hamilton et al. [8] describe a novel 3D-laminated hydrogel platform for coculturing different cell types. This system permits isolation of different cell populations following 3D culture and will facilitate analysis of intercellular interactions in 3D. Understanding and controlling the dynamic interplay between stem cells and the body during complex processes such as vascularization and immune responses will be crucial for obtaining effective clinical outcomes. Wanjare et al. [9] review the role of perivascular cells in blood vessel regeneration. Inclusion of perivascular cells in engineered blood vessels and understanding perivascular interactions with endothelial cells will be crucial in vascularizing stem cell-derived tissue constructs.

This special issue was motivated by the Third International Conference on Stem Cell Engineering, co-sponsored by the Society of Biological Engineering and the International Society for Stem Cell Research, held in Seattle, WA from April 29–May 2, 2012. We thank these societies, the conference sponsors, and all of the conference participants for the enlightening exchange of results and ideas at the meeting. We hope you enjoy the articles in this Special Issue.

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Prof. Brenda M. Ogle, Associate Chair of Graduate Admissions and Associate Professor, Department of Biomedical Engineering, College of Engineering, University of Wisconsin-Madison, WI, USA

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Prof. Sean P. Palecek, Department of Chemical and Biological Engineering, College of Engineering, University of Wisconsin-Madison, WI, USA

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