IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-16065-3.html
   My bibliography  Save this article

Cas9-AAV6-engineered human mesenchymal stromal cells improved cutaneous wound healing in diabetic mice

Author

Listed:
  • Waracharee Srifa

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Nina Kosaric

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Alvaro Amorin

    (Stanford University School of Medicine)

  • Othmane Jadi

    (Stanford University School of Medicine)

  • Yujin Park

    (Stanford University School of Medicine)

  • Sruthi Mantri

    (Stanford University School of Medicine)

  • Joab Camarena

    (Stanford University School of Medicine)

  • Geoffrey C. Gurtner

    (Stanford University School of Medicine)

  • Matthew Porteus

    (Stanford University School of Medicine)

Abstract

Human mesenchymal stromal cells (hMSCs) are a promising source for engineered cell-based therapies in which genetic engineering could enhance therapeutic efficacy and install novel cellular functions. Here, we describe an optimized Cas9-AAV6-based genome editing tool platform for site-specific mutagenesis and integration of up to more than 3 kilobases of exogenous DNA in the genome of hMSCs derived from the bone marrow, adipose tissue, and umbilical cord blood without altering their ex vivo characteristics. We generate safe harbor-integrated lines of engineered hMSCs and show that engineered luciferase-expressing hMSCs are transiently active in vivo in wound beds of db/db mice. Moreover, we generate PDGF-BB- and VEGFA-hypersecreting hMSC lines as short-term, local wound healing agents with superior therapeutic efficacy over wildtype hMSCs in the diabetic mouse model without replacing resident cells long-term. This study establishes a precise genetic engineering platform for genetic studies of hMSCs and development of engineered hMSC-based therapies.

Suggested Citation

  • Waracharee Srifa & Nina Kosaric & Alvaro Amorin & Othmane Jadi & Yujin Park & Sruthi Mantri & Joab Camarena & Geoffrey C. Gurtner & Matthew Porteus, 2020. "Cas9-AAV6-engineered human mesenchymal stromal cells improved cutaneous wound healing in diabetic mice," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16065-3
    DOI: 10.1038/s41467-020-16065-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-16065-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-16065-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Dominic Henn & Dehua Zhao & Dharshan Sivaraj & Artem Trotsyuk & Clark Andrew Bonham & Katharina S. Fischer & Tim Kehl & Tobias Fehlmann & Autumn H. Greco & Hudson C. Kussie & Sylvia E. Moortgat Illouz, 2023. "Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Ron Baik & M. Kyle Cromer & Steve E. Glenn & Christopher A. Vakulskas & Kay O. Chmielewski & Amanda M. Dudek & William N. Feist & Julia Klermund & Suzette Shipp & Toni Cathomen & Daniel P. Dever & Mat, 2024. "Transient inhibition of 53BP1 increases the frequency of targeted integration in human hematopoietic stem and progenitor cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Yonger Xue & Yuebao Zhang & Yichen Zhong & Shi Du & Xucheng Hou & Wenqing Li & Haoyuan Li & Siyu Wang & Chang Wang & Jingyue Yan & Diana D. Kang & Binbin Deng & David W. McComb & Darrell J. Irvine & R, 2024. "LNP-RNA-engineered adipose stem cells for accelerated diabetic wound healing," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16065-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.