bims-cateng Biomed News
on Cell and tissue engineering
Issue of 2023–11–19
seven papers selected by
Chance Bowman, Dartmouth College
  1. Target-dependent RNA polymerase as universal platform for gene expression control in response to intracellular molecules.
  2. From Static to Dynamic: Smart Materials Pioneering Additive Manufacturing in Regenerative Medicine.
  3. Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors.
  4. Skeletal muscle cells opto-stimulation by intramembrane molecular transducers.
  5. Optimal control of gene regulatory networks for morphogen-driven tissue patterning.
  6. Transformable DNA Nanorobots Reversibly Regulating Cell Membrane Receptors for Modulation of Cellular Migrations.
  7. Fundamental properties of smart hydrogels for tissue engineering applications: A review.
  1. Nat Commun. 2023 Nov 17. 14(1): 7256
    Target-dependent RNA polymerase as universal platform for gene expression control in response to intracellular molecules.
    Shodai Komatsu, Hirohisa Ohno, Hirohide Saito.
      Controlling gene expression in response to specific molecules is an essential technique for regulating cellular functions. However, current platforms with transcription and translation regulators have a limited number of detectable molecules to induce gene expression. Here to address these issues, we present a Target-dependent RNA polymerase (TdRNAP) that can induce RNA transcription in response to the intracellular target specifically recognized by single antibody. By substituting the fused antibody, we demonstrate that TdRNAPs respond to a wide variety of molecules, including peptides, proteins, RNA, and small molecules, and produce desired transcripts in human cells. Furthermore, we show that multiple TdRNAPs can construct orthogonal and multilayer genetic circuits. Finally, we apply TdRNAP to achieve cell-specific genome editing that is autonomously triggered by detecting the target gene product. TdRNAP can expand the molecular variety for controlling gene expression and provide the genetic toolbox for bioengineering and future therapeutic applications.
    DOI:  https://doi.org/10.1038/s41467-023-42802-5
  2. Int J Mol Sci. 2023 Oct 30. pii: 15748. [Epub ahead of print]24(21):
    From Static to Dynamic: Smart Materials Pioneering Additive Manufacturing in Regenerative Medicine.
    Antreas Kantaros, Theodore Ganetsos.
      The emerging field of regenerative medicine holds immense promise for addressing complex tissue and organ regeneration challenges. Central to its advancement is the evolution of additive manufacturing techniques, which have transcended static constructs to embrace dynamic, biomimetic solutions. This manuscript explores the pivotal role of smart materials in this transformative journey, where materials are endowed with dynamic responsiveness to biological cues and environmental changes. By delving into the innovative integration of smart materials, such as shape memory polymers and stimulus-responsive hydrogels, into additive manufacturing processes, this research illuminates the potential to engineer tissue constructs with unparalleled biomimicry. From dynamically adapting scaffolds that mimic the mechanical behavior of native tissues to drug delivery systems that respond to physiological cues, the convergence of smart materials and additive manufacturing heralds a new era in regenerative medicine. This manuscript presents an insightful overview of recent advancements, challenges, and future prospects, underscoring the pivotal role of smart materials as pioneers in shaping the dynamic landscape of regenerative medicine and heralding a future where tissue engineering is propelled beyond static constructs towards biomimetic, responsive, and regenerative solutions.
    Keywords:  3D printing; 4D printing; biofabrication; biomedical engineering; biomimetic; dynamic biomaterials; dynamic constructs; regenerative medicine; shape memory polymers; smart materials; tissue engineering; tissue mimicry
    DOI:  https://doi.org/10.3390/ijms242115748
  3. Elife. 2023 Nov 14. pii: RP87081. [Epub ahead of print]12
    Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors.
    Lampros Mavrommatis, Hyun-Woo Jeong, Urs Kindler, Gemma Gomez-Giro, Marie-Cecile Kienitz, Martin Stehling, Olympia E Psathaki, Dagmar Zeuschner, M Gabriele Bixel, Dong Han, Gabriela Morosan-Puopolo, Daniela Gerovska, Ji Hun Yang, Jeong Beom Kim, Marcos J Arauzo-Bravo, Jens C Schwamborn, Stephan A Hahn, Ralf H Adams, Hans R Schöler, Matthias Vorgerd, Beate Brand-Saberi, Holm Zaehres.
      In vitro culture systems that structurally model human myogenesis and promote PAX7+ myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis toward limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single-cell comparison to human fetal and adult myogenic progenitor /satellite cells reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (CD44High/CD98+/MYOD1+) and dormant (PAX7High/FBN1High/SPRY1High) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.
    Keywords:  Myogenesis; Organoids; Pax7; human; ips cells; regenerative medicine; satellite cells; skeletal muscle; stem cells
    DOI:  https://doi.org/10.7554/eLife.87081
  4. Commun Biol. 2023 11 11. 6(1): 1148
    Skeletal muscle cells opto-stimulation by intramembrane molecular transducers.
    Ilaria Venturino, Vito Vurro, Silvio Bonfadini, Matteo Moschetta, Sara Perotto, Valentina Sesti, Luigino Criante, Chiara Bertarelli, Guglielmo Lanzani.
      Optical stimulation and control of muscle cell contraction opens up a number of interesting applications in hybrid robotic and medicine. Here we show that recently designed molecular phototransducer can be used to stimulate C2C12 skeletal muscle cells, properly grown to exhibit collective behaviour. C2C12 is a skeletal muscle cell line that does not require animal sacrifice Furthermore, it is an ideal cell model for evaluating the phototransducer pacing ability due to its negligible spontaneous activity. We study the stimulation process and analyse the distribution of responses in multinuclear cells, in particular looking at the consistency between stimulus and contraction. Contractions are detected by using an imaging software for object recognition. We find a deterministic response to light stimuli, yet with a certain distribution of erratic behaviour that is quantified and correlated to light intensity or stimulation frequency. Finally, we compare our optical stimulation with electrical stimulation showing advantages of the optical approach, like the reduced cell stress.
    DOI:  https://doi.org/10.1038/s42003-023-05538-y
  5. Cell Syst. 2023 Nov 15. pii: S2405-4712(23)00292-2. [Epub ahead of print]14(11): 940-952.e11
    Optimal control of gene regulatory networks for morphogen-driven tissue patterning.
    Alberto Pezzotta, James Briscoe.
      The generation of distinct cell types in developing tissues depends on establishing spatial patterns of gene expression. Often, this is directed by spatially graded chemical signals-known as morphogens. In the "French Flag model," morphogen concentration instructs cells to acquire specific fates. How this mechanism produces timely and organized cell-fate decisions, despite the presence of changing morphogen levels, molecular noise, and individual variability, is unclear. Moreover, feedback is present at various levels in developing tissues, breaking the link between morphogen concentration, signaling activity, and position. Here, we develop an alternative framework using optimal control theory to tackle the problem of morphogen-driven patterning: intracellular signaling is derived as the control strategy that guides cells to the correct fate while minimizing a combination of signaling levels and time. This approach recovers experimentally observed properties of patterning strategies and offers insight into design principles that produce timely, precise, and reproducible morphogen patterning.
    Keywords:  French Flag; control theory; dynamical systems; embryonic development; morphogen; optimal control
    DOI:  https://doi.org/10.1016/j.cels.2023.10.004
  6. ACS Nano. 2023 Nov 15.
    Transformable DNA Nanorobots Reversibly Regulating Cell Membrane Receptors for Modulation of Cellular Migrations.
    Bin Li, Yuning Wang, Baohong Liu.
      Oligomerization of cellular membrane receptors plays crucial roles in activating intracellular downstream signaling cascades for controlling cellular behaviors in physiological and pathological processes. However, the reversible and controllable regulation of receptors in a user-defined manner remains challenging. Herein, we developed a versatile DNA nanorobot (nR) with installed aptamers and hairpin structures to reversibly and controllably regulate cell migration. This was achieved by dimerization and de-dimerization of mesenchymal-epithelial transition (Met) receptors through DNA strand displacement reactions. The functionalized DNA nR not only plays similar roles as hepatocyte growth factor (HGF) in inducing cell migration but also allows a downgrade to the original state of cell migration. The advanced DNA nanomachines can be flexibly designed to target other receptors for manipulating cellular behaviors and thus represent a powerful tool for the future of biological and medical engineering.
    Keywords:  DNA nanotechnology; aptamers; cellular behaviors; receptors; reversible manipulation
    DOI:  https://doi.org/10.1021/acsnano.3c06305
  7. Int J Biol Macromol. 2023 Nov 10. pii: S0141-8130(23)04781-5. [Epub ahead of print]254(Pt 3): 127882
    Fundamental properties of smart hydrogels for tissue engineering applications: A review.
    Muhammad Umar Aslam Khan, Goran M Stojanović, Mohd Faizal Bin Abdullah, Alireza Dolatshahi-Pirouz, Hany E Marei, Nureddin Ashammakhi, Anwarul Hasan.
      Tissue engineering is an advanced and potential biomedical approach to treat patients suffering from lost or failed an organ or tissue to repair and regenerate damaged tissues that increase life expectancy. The biopolymers have been used to fabricate smart hydrogels to repair damaged tissue as they imitate the extracellular matrix (ECM) with intricate structural and functional characteristics. These hydrogels offer desired and controllable qualities, such as tunable mechanical stiffness and strength, inherent adaptability and biocompatibility, swellability, and biodegradability, all crucial for tissue engineering. Smart hydrogels provide a superior cellular environment for tissue engineering, enabling the generation of cutting-edge synthetic tissues due to their special qualities, such as stimuli sensitivity and reactivity. Numerous review articles have presented the exceptional potential of hydrogels for various biomedical applications, including drug delivery, regenerative medicine, and tissue engineering. Still, it is essential to write a comprehensive review article on smart hydrogels that successfully addresses the essential challenging issues in tissue engineering. Hence, the recent development on smart hydrogel for state-of-the-art tissue engineering conferred progress, highlighting significant challenges and future perspectives. This review discusses recent advances in smart hydrogels fabricated from biological macromolecules and their use for advanced tissue engineering. It also provides critical insight, emphasizing future research directions and progress in tissue engineering.
    Keywords:  Biopolymers; Fundamental properties; Smart hydrogels; Tissue engineering
    DOI:  https://doi.org/10.1016/j.ijbiomac.2023.127882
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