bims-cateng Biomed News
on Cell and tissue engineering
Issue of 2023‒10‒01
seven papers selected by
Chance Bowman, Dartmouth College
  1. Human embryo models offer glimpse into early development.
  2. Bioprocessing Considerations towards the Manufacturing of Therapeutic Skeletal and Smooth Muscle Cells.
  3. Evolution of CRISPR/Cas Systems for Precise Genome Editing.
  4. Recent Advances in Stem Cell Differentiation Control Using Drug Delivery Systems Based on Porous Functional Materials.
  5. Creation of an iPSC-Based Skeletal Muscle Model of McArdle Disease Harbouring the Mutation c.2392T>C (p.Trp798Arg) in the PYGM Gene.
  6. Protein-based delivery systems for RNA delivery.
  7. Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases.
  1. Nat Med. 2023 Sep 25.
    Human embryo models offer glimpse into early development.
    Karen O'Leary.
      
    Keywords:  Embryology; Stem cells; Technology
    DOI:  https://doi.org/10.1038/d41591-023-00083-x
  2. Bioengineering (Basel). 2023 Sep 09. pii: 1067. [Epub ahead of print]10(9):
    Bioprocessing Considerations towards the Manufacturing of Therapeutic Skeletal and Smooth Muscle Cells.
    Teresa Franchi-Mendes, Marília Silva, Ana Luísa Cartaxo, Ana Fernandes-Platzgummer, Joaquim M S Cabral, Cláudia L da Silva.
      Tissue engineering approaches within the muscle context represent a promising emerging field to address the current therapeutic challenges related with multiple pathological conditions affecting the muscle compartments, either skeletal muscle or smooth muscle, responsible for involuntary and voluntary contraction, respectively. In this review, several features and parameters involved in the bioprocessing of muscle cells are addressed. The cell isolation process is depicted, depending on the type of tissue (smooth or skeletal muscle), followed by the description of the challenges involving the use of adult donor tissue and the strategies to overcome the hurdles of reaching relevant cell numbers towards a clinical application. Specifically, the use of stem/progenitor cells is highlighted as a source for smooth and skeletal muscle cells towards the development of a cellular product able to maintain the target cell's identity and functionality. Moreover, taking into account the need for a robust and cost-effective bioprocess for cell manufacturing, the combination of muscle cells with biomaterials and the need for scale-up envisioning clinical applications are also approached.
    Keywords:  cell manufacturing; skeletal muscle cells; smooth muscle cells; tissue engineering
    DOI:  https://doi.org/10.3390/bioengineering10091067
  3. Int J Mol Sci. 2023 Sep 18. pii: 14233. [Epub ahead of print]24(18):
    Evolution of CRISPR/Cas Systems for Precise Genome Editing.
    Magdalena Hryhorowicz, Daniel Lipiński, Joanna Zeyland.
      The bacteria-derived CRISPR/Cas (an acronym for regularly interspaced short palindromic repeats/CRISPR-associated protein) system is currently the most widely used, versatile, and convenient tool for genome engineering. CRISPR/Cas-based technologies have been applied to disease modeling, gene therapies, transcriptional modulation, and diagnostics. Nevertheless, some challenges remain, such as the risk of immunological reactions or off-target effects. To overcome these problems, many new methods and CRISPR/Cas-based tools have been developed. In this review, we describe the current classification of CRISPR systems and new precise genome-editing technologies, summarize the latest applications of this technique in several fields of research, and, finally, discuss CRISPR/Cas system limitations, ethical issues, and challenges.
    Keywords:  CRISPR classification; CRISPR/Cas9 system; Cas12a nuclease; Cas13a nuclease; Cas9 nuclease; base editors; genome editing; prime editors
    DOI:  https://doi.org/10.3390/ijms241814233
  4. J Funct Biomater. 2023 Sep 20. pii: 483. [Epub ahead of print]14(9):
    Recent Advances in Stem Cell Differentiation Control Using Drug Delivery Systems Based on Porous Functional Materials.
    Yun-Sik Eom, Joon-Ha Park, Tae-Hyung Kim.
      The unique characteristics of stem cells, which include self-renewal and differentiation into specific cell types, have paved the way for the development of various biomedical applications such as stem cell therapy, disease modelling, and drug screening. The establishment of effective stem cell differentiation techniques is essential for the effective application of stem cells for various purposes. Ongoing research has sought to induce stem cell differentiation using diverse differentiation factors, including chemicals, proteins, and integrin expression. These differentiation factors play a pivotal role in a variety of applications. However, it is equally essential to acknowledge the potential hazards of uncontrolled differentiation. For example, uncontrolled differentiation can give rise to undesirable consequences, including cancerous mutations and stem cell death. Therefore, the development of innovative methods to control stem cell differentiation is crucial. In this review, we discuss recent research cases that have effectively utilised porous functional material-based drug delivery systems to regulate stem cell differentiation. Due to their unique substrate properties, drug delivery systems based on porous functional materials effectively induce stem cell differentiation through the steady release of differentiation factors. These ground-breaking techniques hold considerable promise for guiding and controlling the fate of stem cells for a wide range of biomedical applications, including stem cell therapy, disease modelling, and drug screening.
    Keywords:  differentiation control; drug delivery system; porous particle; stem cell
    DOI:  https://doi.org/10.3390/jfb14090483
  5. Biomedicines. 2023 Aug 31. pii: 2434. [Epub ahead of print]11(9):
    Creation of an iPSC-Based Skeletal Muscle Model of McArdle Disease Harbouring the Mutation c.2392T>C (p.Trp798Arg) in the PYGM Gene.
    Victoria Cerrada, Inés García-Consuegra, Joaquín Arenas, M Esther Gallardo.
      McArdle disease is a rare autosomal recessive condition caused by mutations in the PYGM gene. This gene encodes the skeletal muscle isoform of glycogen phosphorylase or myophosphorylase. Patients with McArdle disease have an inability to obtain energy from their muscle glycogen stores, which manifests as a marked exercise intolerance. Nowadays, there is no cure for this disorder and recommendations are intended to prevent and mitigate symptoms. There is great heterogeneity among the pathogenic variants found in the PYGM gene, and there is no obvious correlation between genotypes and phenotypes. Here, we present the generation of the first human iPSC-based skeletal muscle model harbouring the second most frequent mutation in PYGM in the Spanish population: NM_005609.4: c.2392T>C (p.Trp798Arg). To this end, iPSCs derived from a McArdle patient and a healthy control were both successfully differentiated into skeletal muscle cells using a small molecule-based protocol. The created McArdle skeletal muscle model was validated by confirming distinctive biochemical aspects of the disease such as the absence of myophosphorylase, the most typical biochemical feature of these patients. This model will be very valuable for use in future high-throughput pharmacological screenings.
    Keywords:  McArdle disease; PYGM; disease modelling; iPSCs; induced pluripotent stem cell; skeletal muscle differentiation
    DOI:  https://doi.org/10.3390/biomedicines11092434
  6. J Control Release. 2023 Sep 21. pii: S0168-3659(23)00619-3. [Epub ahead of print]
    Protein-based delivery systems for RNA delivery.
    Haichao Zhu, Hong Luo, Ruilong Chang, Yifan Yang, Dingkang Liu, Yue Ji, Hai Qin, Haibo Rong, Jun Yin.
      RNA-based therapeutics have emerged as promising approaches to modulate gene expression and generate therapeutic proteins or antigens capable of inducing immune responses to treat a variety of diseases, such as infectious diseases, cancers, immunologic disorders, and genetic disorders. However, the efficient delivery of RNA molecules into cells poses significant challenges due to their large molecular weight, negative charge, and susceptibility to degradation by RNase enzymes. To overcome these obstacles, viral and non-viral vectors have been developed, including lipid nanoparticles, viral vectors, proteins, dendritic macromolecules, among others. Among these carriers, protein-based delivery systems have garnered considerable attention due to their potential to address specific issues associated with nanoparticle-based systems, such as liver accumulation and immunogenicity. This review provides an overview of currently marketed RNA drugs, underscores the significance of RNA delivery vector development, delineates the essential characteristics of an ideal RNA delivery vector, and introduces existing protein carriers for RNA delivery. By offering valuable insights, this review aims to serve as a reference for the future development of protein-based delivery vectors for RNA therapeutics.
    Keywords:  Delivery vectors; Protein carriers; RNA delivery challenges; RNA drug; RNA-based therapeutics
    DOI:  https://doi.org/10.1016/j.jconrel.2023.09.032
  7. bioRxiv. 2023 Sep 13. pii: 2023.09.12.557440. [Epub ahead of print]
    Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases.
    Joana Ferreira da Silva, Connor J Tou, Emily M King, Madeline L Eller, Linyuan Ma, David Rufino-Ramos, Benjamin P Kleinstiver.
      Genome editing technologies that install diverse edits can widely enable genetic studies and new therapeutics. Here we develop click editing, a genome writing platform that couples the advantageous properties of DNA-dependent DNA polymerases with RNA-programmable nickases (e.g. CRISPR-Cas) to permit the installation of a range of edits including substitutions, insertions, and deletions. Click editors (CEs) leverage the "click"-like bioconjugation ability of HUH endonucleases (HUHes) with single stranded DNA substrates to covalently tether "click DNA" (clkDNA) templates encoding user-specifiable edits at targeted genomic loci. Through iterative optimization of the modular components of CEs (DNA polymerase and HUHe orthologs, architectural modifications, etc.) and their clkDNAs (template configurations, repair evading substitutions, etc.), we demonstrate the ability to install precise genome edits with minimal indels and no unwanted byproduct insertions. Since clkDNAs can be ordered as simple DNA oligonucleotides for cents per base, it is possible to screen many different clkDNA parameters rapidly and inexpensively to maximize edit efficiency. Together, click editing is a precise and highly versatile platform for modifying genomes with a simple workflow and broad utility across diverse biological applications.
    DOI:  https://doi.org/10.1101/2023.09.12.557440
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