Article

Engineering Three-Dimensional Stem Cell Morphogenesis for the Development of Tissue Models and Scalable Regenerative Therapeutics

The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, 313 Ferst Drive, Atlanta, GA, 30332-0532, USA.
Annals of Biomedical Engineering (Impact Factor: 3.23). 12/2013; 42(2). DOI: 10.1007/s10439-013-0953-9
Source: PubMed

ABSTRACT The physiochemical stem cell microenvironment regulates the delicate balance between self-renewal and differentiation. The three-dimensional assembly of stem cells facilitates cellular interactions that promote morphogenesis, analogous to the multicellular, heterotypic tissue organization that accompanies embryogenesis. Therefore, expansion and differentiation of stem cells as multicellular aggregates provides a controlled platform for studying the biological and engineering principles underlying spatiotemporal morphogenesis and tissue patterning. Moreover, three-dimensional stem cell cultures are amenable to translational screening applications and therapies, which underscores the broad utility of scalable suspension cultures across laboratory and clinical scales. In this review, we discuss stem cell morphogenesis in the context of fundamental biophysical principles, including the three-dimensional modulation of adhesions, mechanics, and molecular transport and highlight the opportunities to employ stem cell spheroids for tissue modeling, bioprocessing, and regenerative therapies.

1 Bookmark
 · 
72 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human pluripotent stem cells (hPSCs) provide promising resources for regenerating tissues and organs and modeling development and diseases in vitro. To fulfill their promise, the fate, function, and organization of hPSCs need to be precisely regulated in a three-dimensional (3D) environment to mimic cellular structures and functions of native tissues and organs. In the past decade, innovations in 3D culture systems with functional biomaterials have enabled efficient and versatile control of hPSC fate at the cellular level. However, we are just at the beginning of bringing hPSC-based regeneration and development and disease modeling to the tissue and organ levels. In this review, we summarize existing bioengineered culture platforms for controlling hPSC fate and function by regulating inductive mechanical and biochemical cues coexisting in the synthetic cell microenvironment. We highlight recent excitements in developing 3D hPSC-based in vitro tissue and organ models with in vivo-like cellular structures, interactions, and functions. We further discuss an emerging multifaceted mechanotransductive signaling network – with transcriptional coactivators YAP and TAZ at the center stage – that regulate fates and behaviors of mammalian cells, including hPSCs. Future development of 3D biomaterial systems should incorporate dynamically modulated mechanical and chemical properties targeting specific intracellular signaling events leading to desirable hPSC fate patterning and functional tissue formation in 3D.
    Biomaterials 06/2015; 52. DOI:10.1016/j.biomaterials.2015.01.078 · 8.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Industrial sectors perform toxicological assessments of their potential products to ensure human safety and to fulfil regulatory requirements. These assessments often involve animal testing but ethical, cost and time concerns, together with a ban on it in specific sectors, make appropriate in vitro systems indispensable in toxicology. Here, we summarize the outcome of an EPAA (European Partnership of Alternatives to Animal Testing)-organized workshop on the use of stem cell derived (SCD)-systems in toxicology, with a focus on industrial applications. SCD-systems, in particular iPSC-derived, provide physiological cell culture systems of easy access and amenable to a variety of assays. They also present the opportunity to apply the vast repository of existing non-clinical data for the understanding of in vitro to in vivo translation. SCD-systems from several toxicologically relevant tissues exist; they generally recapitulate many aspects of physiology and respond to toxicological and pharmacological interventions. However, focused research is necessary to accelerate implementation of SCD-systems in an industrial setting and subsequent use of such systems by regulatory authorities. Research is required into the phenotypic characterization of the systems, since methods and protocols for generating terminally differentiated SCD-cells are still lacking. Organotypical, 3D-culture systems in bioreactors and microscale tissue engineering technologies should be fostered, as they promote and maintain differentiation and support co-culture systems. They need further development and validation for their successful implementation in toxicity testing in industry. Analytical measures also need to be implemented to enable compound exposure and metabolism measurements for in vitro to in vivo extrapolation. The future of SCD-toxicological tests will combine advanced cell culture technologies and biokinetic measurements to support regulatory and research applications. However, scientific and technical hurdles must be overcome before SCD-in vitro methods undergo appropriate validation and become accepted in the regulatory arena.
  • Source
    Nano Today 01/2015; DOI:10.1016/j.nantod.2014.12.002 · 18.43 Impact Factor

Full-text

Download
16 Downloads
Available from
May 20, 2014