ASU Scholarship Showcase

Due to the limitation of current pharmacological therapeutic strategies, stem cell therapies have emerged as a viable option for treating many incurable neurological disorders. Specifically, human pluripotent stem cell (hPSC)-derived neural progenitor cells (hNPCs), a multipotent cell population that is capable of near indefinite expansion and subsequent differentiation into the various cell types that comprise the central nervous system (CNS), could provide an unlimited source of cells for such cell-based therapies. However the clinical application of these cells will require (i) defined, xeno-free conditions for their expansion and neuronal differentiation and (ii) scalable culture systems that enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug screening purposes. Current extracellular matrix protein (ECMP)-based substrates for the culture of hNPCs are expensive, difficult to isolate, subject to batch-to-batch variations, and, therefore, unsuitable for clinical application of hNPCs. Using a high-throughput array-based screening approach, we identified a synthetic polymer, poly(4-vinyl phenol) (P4VP), that supported the long-term proliferation and self-renewal of hNPCs. The hNPCs cultured on P4VP maintained their characteristic morphology, expressed high levels of markers of multipotency, and retained their ability to differentiate into neurons. Such chemically defined substrates will eliminate critical roadblocks for the utilization of hNPCs for human neural regenerative repair, disease modeling, and drug discovery.

Adult and pluripotent stem cells represent a ready supply of cellular raw materials that can be used to generate the functionally mature cells needed to replace damaged or diseased heart tissue. However, the use of stem cells for cardiac regenerative therapies is limited by the low efficiency by which stem cells are differentiated in vitro to cardiac lineages as well as the inability to effectively deliver stem cells and their derivatives to regions of damaged myocardium. In this review, we discuss the various biomaterial-based approaches that are being implemented to direct stem cell fate both in vitro and in vivo. First, we discuss the stem cell types available for cardiac repair and the engineering of naturally and synthetically derived biomaterials to direct their in vitro differentiation to the cell types that comprise heart tissue. Next, we describe biomaterial-based approaches that are being implemented to enhance the in vivo integration and differentiation of stem cells delivered to areas of cardiac damage. Finally, we present emerging trends of using stem cell-based biomaterial approaches to deliver pro-survival factors and fully vascularized tissue to the damaged and diseased cardiac tissue.

The field of tissue engineering entered a new era with the development of human pluripotent stem cells (hPSCs), which are capable of unlimited expansion whilst retaining the potential to differentiate into all mature cell populations. However, these cells harbor significant risks, including tumor formation upon transplantation. One way to mitigate this risk is to develop expandable progenitor cell populations with restricted differentiation potential. Here, we used a cellular microarray technology to identify a defined and optimized culture condition that supports the derivation and propagation of a cell population with mesodermal properties. This cell population, referred to as intermediate mesodermal progenitor (IMP) cells, is capable of unlimited expansion, lacks tumor formation potential, and, upon appropriate stimulation, readily acquires properties of a sub-population of kidney cells. Interestingly, IMP cells fail to differentiate into other mesodermally-derived tissues, including blood and heart, suggesting that these cells are restricted to an intermediate mesodermal fate.

Using the City of Roanoke, Virginia as a study site, this paper quantifies the forest structure, ecosystem services and values of vacant and residential land. Single family residential land had more trees (1,683,000) than vacant land (210,000) due largely to the differences in land area (32.44 km² of vacant land vs. 57.94 km² residential). While the percentage of tree coverage was almost identical across land uses (30.6% in vacant to 32.3% in residential), the number of trees per ha is greater on residential land (290.3) than on vacant land (63.4). The average healthy leaf surface area on individual trees growing on vacant land was greater than that of individual trees on residential land. The fact that trees in vacant land were found to provide more ecosystem services per tree than residential trees was attributed to this leaf area difference. Trees on vacant land are growing in more natural conditions and there are more large trees per ha. Assessing the forest structure and ecosystem services of Roanoke’s vacant and residential land provides a picture of the current extent and condition of the vacant and residential land. Understanding these characteristics provides the information needed for improved management and utilization of urban vacant land and estimating green infrastructure value.

This study reviews scholarly papers and case studies on urban vacant land to gain a stronger understanding of its public value in terms of the ecological and social benefits it can bring. This literature review offers a conceptual overview of the potential benefits of vacant land with the goal of addressing gaps in knowledge about vacant land and to provide suggestions to planners and designers on how vacant properties can be integrated with other green infrastructure in cities. There are many opportunities to redevelop vacant land to enhance its ecological and social value, and many design professionals and scholars are becoming interested in finding new ways to exploit this potential, especially with regard to planning and design. A better appreciation of the public value of urban vacant land is vital for any effort to identify alternative strategies to optimize the way these spaces are utilized for both short-term and long-term uses to support urban regeneration and renewal. This study will help planners and designers to understand and plan for urban vacant land, leading to better utilization of these spaces and opening up alternative creative approaches to envisioning space and landscape design in our urban environments.

In the decade since Yamanaka and colleagues described methods to reprogram somatic cells into a pluripotent state, human induced pluripotent stem cells (hiPSCs) have demonstrated tremendous promise in numerous disease modeling, drug discovery, and regenerative medicine applications. More recently, the development and refinement of advanced gene transduction and editing technologies have further accelerated the potential of hiPSCs. In this review, we discuss the various gene editing technologies that are being implemented with hiPSCs. Specifically, we describe the emergence of technologies including zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 that can be used to edit the genome at precise locations, and discuss the strengths and weaknesses of each of these technologies. In addition, we present the current applications of these technologies in elucidating the mechanisms of human development and disease, developing novel and effective therapeutic molecules, and engineering cell-based therapies. Finally, we discuss the emerging technological advances in targeted gene editing methods.

Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.

An urban forest assessment is essential for developing a baseline from which to measure changes and trends. The most precise way to assess urban forests is to measure and record every tree on a site, but although this may work well for relatively small populations (e.g., street trees, small parks), it is prohibitively expensive for large tree populations. Thus, random sampling offers a cost-effective way to assess urban forest structure and the associated ecosystem services for large-scale assessments. The methodology applied to assess ecosystem services in this study can also be used to assess the ecosystem services provided by vacant land in other urban contexts and improve urban forest policies, planning, and the management of vacant land. The study’s findings support the inclusion of trees on vacant land and contribute to a new vision of vacant land as a valuable ecological resource by demonstrating how green infrastructure can be used to enhance ecosystem health and promote a better quality of life for city residents.

Background: Few existing interactive rehabilitation systems can effectively communicate multiple aspects of movement performance simultaneously, in a manner that appropriately adapts across various training scenarios. In order to address the need for such systems within stroke rehabilitation training, a unified approach for designing interactive systems for upper limb rehabilitation of stroke survivors has been developed and applied for the implementation of an Adaptive Mixed Reality Rehabilitation (AMRR) System.

Results: The AMRR system provides computational evaluation and multimedia feedback for the upper limb rehabilitation of stroke survivors. A participant's movements are tracked by motion capture technology and evaluated by computational means. The resulting data are used to generate interactive media-based feedback that communicates to the participant detailed, intuitive evaluations of his performance. This article describes how the AMRR system's interactive feedback is designed to address specific movement challenges faced by stroke survivors. Multimedia examples are provided to illustrate each feedback component. Supportive data are provided for three participants of varying impairment levels to demonstrate the system's ability to train both targeted and integrated aspects of movement.

Conclusions: The AMRR system supports training of multiple movement aspects together or in isolation, within adaptable sequences, through cohesive feedback that is based on formalized compositional design principles. From preliminary analysis of the data, we infer that the system's ability to train multiple foci together or in isolation in adaptable sequences, utilizing appropriately designed feedback, can lead to functional improvement. The evaluation and feedback frameworks established within the AMRR system will be applied to the development of a novel home-based system to provide an engaging yet low-cost extension of training for longer periods of time.

Background: Although principles based in motor learning, rehabilitation, and human-computer interfaces can guide the design of effective interactive systems for rehabilitation, a unified approach that connects these key principles into an integrated design, and can form a methodology that can be generalized to interactive stroke rehabilitation, is presently unavailable.

Results: This paper integrates phenomenological approaches to interaction and embodied knowledge with rehabilitation practices and theories to achieve the basis for a methodology that can support effective adaptive, interactive rehabilitation. Our resulting methodology provides guidelines for the development of an action representation, quantification of action, and the design of interactive feedback. As Part I of a two-part series, this paper presents key principles of the unified approach. Part II then describes the application of this approach within the implementation of the Adaptive Mixed Reality Rehabilitation (AMRR) system for stroke rehabilitation.

Conclusions: The accompanying principles for composing novel mixed reality environments for stroke rehabilitation can advance the design and implementation of effective mixed reality systems for the clinical setting, and ultimately be adapted for home-based application. They furthermore can be applied to other rehabilitation needs beyond stroke.