Stem Cell Engineering

This report provides an assessment of the state of stem cell engineering (SCE) globally. This is based on a yearlong study that was conducted by six panel members and managed by the World Technology Evaluation Center (WTEC). This opening chapter provides background for this study, outlines the scope of the study, identifies the six panel members, describes the study process, provides an overview of the principal findings, and finally states conclusions that hopefully provide the basis for stem cell engineering moving forward and for the acceleration of the progress being made in the broad field of stem cells.

Biological research in general is becoming increasingly interdisciplinary, and stem cell research in particular has strong potential to become progressively more so. In this field, there has for example been a growing recognition that, while biochemical signals play critical roles in regulating the behavior and fate decisions of stem cells, biology presents regulatory information to cells not only in the binary absence or presence of a given molecule, but also numerous biophysical aspects of these regulatory cues. These include mechanics, topographical features at multiple size scales, electrostatics, spatiotemporal variation in the presentation of biochemical cues, transport phenomena, and biochemical reaction kinetics. As a result, there are considerable opportunities for physical scientists and engineers to become increasingly involved in stem cell research, not only to gain basic insights into new mechanisms in stem cell biology but to create new technologies to advance this field. Within this report, chapter “High-throughput Screening, Microfluidics, Biosensors, and Real-time Phenotyping” discusses the development of technologies to discover novel signals that regulate stem cell behavior, and chapter “Computational Modeling and Stem Cell Engineering” reviews progress in the development of mathematical models that quantitatively investigate the underlying regulatory mechanisms. The present chapter will review research into now biophysical features of the microenvironment or niche regulate the behavior of a stem cell.

Key opportunities for the field of stem cell engineering involve identification of cues that regulate stem cell fate, constructing a systems level understanding of how cells sense and process information provided by the microenvironment, and designing environments to elicit the desired cell fate. Meeting these opportunities will be facilitated by collaborative, interdisciplinary interactions among engineers, scientists, and clinicians. Chapters “Physical and Engineering Principles in Stem Cell Research” and “Computational Modeling and Stem Cell Engineering” in this report address the principles by which physical cues can affect stem cells and how mathematical modeling can provide insight into mechanisms of stem cell regulation. For these efforts to be successful, spatial and dynamic control over the microenvironment is needed. This chapter will focus on how recent advances in cell culture platform design and manufacture permit systematic application of regulatory cues to stem cells, and the insight these systems have provided in stem cell biology and engineering.

A key goal of regenerative medicine and bioengineering is the quantitative and robust control over the fate and behavior of individual cells and their populations, both in vitro and in vivo. Central to this endeavor are stem cells (SCs), which can be functionally defined as undifferentiated cells of a multicellular organism that balance the capacity for sustained self-renewal with the potential to differentiate into specialized cell types. The biology of multicellular organisms necessitates the existence and precise control of SCs to facilitate development from a single cell during embryogenesis, and tissue homeostasis in the face of continual loss of terminally differentiated cells. It is therefore not surprising that SCs have been identified and isolated from numerous adult human tissues, as well as more recently, the inner cell mass of the preimplantation human blastocyst. SCs promise a renewable source of human tissue for research, pharmaceutical testing, and cell-based therapies. Fulfilling this promise will require not only the precise control of SC self-renewal and differentiation, but also imposing this control on the formation of more functionally complex tissue-like structures.

The ability to manufacture products from stem cells is required to deliver on the many envisioned potential applications of these cells and will ultimately dictate the translational success of stem cells. The technologies and processes for bioprocessing are dependent on insights gained from the physical science principles, screening technologies, and computational analysis approaches described in each of the previous chapters. Ultimately insights from each of these different approaches will contribute significantly to the different elements of biomanufacturing schemes including culture platforms, monitoring techniques, and quality control/assurance. The development and implementation of bioprocessing technologies will require collaborations between academic institutions and a rapidly growing global industry seeking to commercialize stem cell products, as well as interactions with regulatory agencies providing oversight of these processes. This chapter will highlight the most common current approaches and remaining challenges facing the development of bioprocessing technologies necessary for the scalable and robust manufacturing of stem cells and stem cell-derived products.