IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50054-0.html
   My bibliography  Save this article

Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells

Author

Listed:
  • Hannah Donnelly

    (University of Glasgow)

  • Ewan Ross

    (University of Glasgow)

  • Yinbo Xiao

    (University of Glasgow)

  • Rio Hermantara

    (University of Glasgow)

  • Aqeel F. Taqi

    (University of Glasgow)

  • W. Sebastian Doherty-Boyd

    (University of Glasgow)

  • Jennifer Cassels

    (University of Glasgow)

  • Penelope. M. Tsimbouri

    (University of Glasgow)

  • Karen M. Dunn

    (University of Glasgow)

  • Jodie Hay

    (University of Glasgow)

  • Annie Cheng

    (University of Glasgow)

  • R. M. Dominic Meek

    (Queen Elizabeth University Hospital)

  • Nikhil Jain

    (Queen Elizabeth Hospital)

  • Christopher West

    (The University of Edinburgh)

  • Helen Wheadon

    (University of Glasgow)

  • Alison M. Michie

    (University of Glasgow)

  • Bruno Peault

    (The University of Edinburgh)

  • Adam G. West

    (University of Glasgow)

  • Manuel Salmeron-Sanchez

    (University of Glasgow)

  • Matthew J. Dalby

    (University of Glasgow)

Abstract

Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via stem cell transplantation. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs and progenitor populations at the expense of naive LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1α expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1α expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders.

Suggested Citation

  • Hannah Donnelly & Ewan Ross & Yinbo Xiao & Rio Hermantara & Aqeel F. Taqi & W. Sebastian Doherty-Boyd & Jennifer Cassels & Penelope. M. Tsimbouri & Karen M. Dunn & Jodie Hay & Annie Cheng & R. M. Domi, 2024. "Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50054-0
    DOI: 10.1038/s41467-024-50054-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50054-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50054-0?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
    ---><---

    References listed on IDEAS

    as
    1. Leonard I. Zon, 2008. "Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal," Nature, Nature, vol. 453(7193), pages 306-313, May.
    2. Lei Ding & Sean J. Morrison, 2013. "Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches," Nature, Nature, vol. 495(7440), pages 231-235, March.
    3. Joel A. Spencer & Francesca Ferraro & Emmanuel Roussakis & Alyssa Klein & Juwell Wu & Judith M. Runnels & Walid Zaher & Luke J. Mortensen & Clemens Alt & Raphaël Turcotte & Rushdia Yusuf & Daniel Côté, 2014. "Direct measurement of local oxygen concentration in the bone marrow of live animals," Nature, Nature, vol. 508(7495), pages 269-273, April.
    4. Yuya Kunisaki & Ingmar Bruns & Christoph Scheiermann & Jalal Ahmed & Sandra Pinho & Dachuan Zhang & Toshihide Mizoguchi & Qiaozhi Wei & Daniel Lucas & Keisuke Ito & Jessica C. Mar & Aviv Bergman & Pau, 2013. "Arteriolar niches maintain haematopoietic stem cell quiescence," Nature, Nature, vol. 502(7473), pages 637-643, October.
    5. L. M. Calvi & G. B. Adams & K. W. Weibrecht & J. M. Weber & D. P. Olson & M. C. Knight & R. P. Martin & E. Schipani & P. Divieti & F. R. Bringhurst & L. A. Milner & H. M. Kronenberg & D. T. Scadden, 2003. "Osteoblastic cells regulate the haematopoietic stem cell niche," Nature, Nature, vol. 425(6960), pages 841-846, October.
    6. Ewan A. Ross & Lesley-Anne Turner & Hannah Donnelly & Anwer Saeed & Monica P. Tsimbouri & Karl V. Burgess & Gavin Blackburn & Vineetha Jayawarna & Yinbo Xiao & Mariana A. G. Oliva & Jennifer Willis & , 2023. "Nanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Bo Shen & Alpaslan Tasdogan & Jessalyn M. Ubellacker & Jingzhu Zhang & Elena D. Nosyreva & Liming Du & Malea M. Murphy & Shuiqing Hu & Yating Yi & Nergis Kara & Xin Liu & Shay Guela & Yuemeng Jia & Vi, 2021. "A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis," Nature, Nature, vol. 591(7850), pages 438-444, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Adrienne Anginot & Julie Nguyen & Zeina Abou Nader & Vincent Rondeau & Amélie Bonaud & Maria Kalogeraki & Antoine Boutin & Julia P. Lemos & Valeria Bisio & Joyce Koenen & Lea Hanna Doumit Sakr & Amand, 2023. "WHIM Syndrome-linked CXCR4 mutations drive osteoporosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Tiago C. Luis & Nikolaos Barkas & Joana Carrelha & Alice Giustacchini & Stefania Mazzi & Ruggiero Norfo & Bishan Wu & Affaf Aliouat & Jose A. Guerrero & Alba Rodriguez-Meira & Tiphaine Bouriez-Jones &, 2023. "Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Qiang Zhao & Young-Min Han & Ping Song & Zhixue Liu & Zuyi Yuan & Ming-Hui Zou, 2022. "Endothelial cell-specific expression of serine/threonine kinase 11 modulates dendritic cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Haoqing Jerry Wang & Yao Wang & Seyed Sajad Mirjavadi & Tomas Andersen & Laura Moldovan & Parham Vatankhah & Blake Russell & Jasmine Jin & Zijing Zhou & Qing Li & Charles D. Cox & Qian Peter Su & Lini, 2024. "Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Xianzhu Zhang & Wei Jiang & Chang Xie & Xinyu Wu & Qian Ren & Fei Wang & Xilin Shen & Yi Hong & Hongwei Wu & Youguo Liao & Yi Zhang & Renjie Liang & Wei Sun & Yuqing Gu & Tao Zhang & Yishan Chen & Wei, 2022. "Msx1+ stem cells recruited by bioactive tissue engineering graft for bone regeneration," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    6. Yang Liu & Qi Chen & Hyun-Woo Jeong & Bong Ihn Koh & Emma C. Watson & Cong Xu & Martin Stehling & Bin Zhou & Ralf H. Adams, 2022. "A specialized bone marrow microenvironment for fetal haematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Taichi Nakatani & Tatsuki Sugiyama & Yoshiki Omatsu & Hitomi Watanabe & Gen Kondoh & Takashi Nagasawa, 2023. "Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Young-Woong Kim & Greta Zara & HyunJun Kang & Sergio Branciamore & Denis O’Meally & Yuxin Feng & Chia-Yi Kuan & Yingjun Luo & Michael S. Nelson & Alex B. Brummer & Russell Rockne & Zhen Bouman Chen & , 2022. "Integration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelium," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Hyuek Jong Lee & Jueun Lee & Myung Jin Yang & Young-Chan Kim & Seon Pyo Hong & Jung Mo Kim & Geum-Sook Hwang & Gou Young Koh, 2023. "Endothelial cell-derived stem cell factor promotes lipid accumulation through c-Kit-mediated increase of lipogenic enzymes in brown adipocytes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Alexandra N. Rindone & Xiaonan Liu & Stephanie Farhat & Alexander Perdomo-Pantoja & Timothy F. Witham & Daniel L. Coutu & Mei Wan & Warren L. Grayson, 2021. "Quantitative 3D imaging of the cranial microvascular environment at single-cell resolution," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    11. Runfeng Miao & Harim Chun & Xing Feng & Ana Cordeiro Gomes & Jungmin Choi & João P. Pereira, 2022. "Competition between hematopoietic stem and progenitor cells controls hematopoietic stem cell compartment size," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    12. Géraldine Poncin & Aurore Beaulieu & Chantal Humblet & Albert Thiry & Kimimitsu Oda & Jacques Boniver & Marie-Paule Defresne, 2012. "Characterization of Spontaneous Bone Marrow Recovery after Sublethal Total Body Irradiation: Importance of the Osteoblastic/Adipocytic Balance," PLOS ONE, Public Library of Science, vol. 7(2), pages 1-13, February.
    13. Nathalia G. Amado & Elena D. Nosyreva & David Thompson & Thomas J. Egeland & Osita W. Ogujiofor & Michelle Yang & Alexandria N. Fusco & Niccolo Passoni & Jeremy Mathews & Brandi Cantarel & Linda A. Ba, 2024. "PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    14. Lorand Gabriel Parajdi & Radu Precup & Eduard Alexandru Bonci & Ciprian Tomuleasa, 2020. "A Mathematical Model of the Transition from Normal Hematopoiesis to the Chronic and Accelerated-Acute Stages in Myeloid Leukemia," Mathematics, MDPI, vol. 8(3), pages 1-18, March.
    15. Christina M. Termini & Amara Pang & Tiancheng Fang & Martina Roos & Vivian Y. Chang & Yurun Zhang & Nicollette J. Setiawan & Lia Signaevskaia & Michelle Li & Mindy M. Kim & Orel Tabibi & Paulina K. Li, 2021. "Neuropilin 1 regulates bone marrow vascular regeneration and hematopoietic reconstitution," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    16. Xue Zhong & Nagesh Peddada & Jianhui Wang & James J. Moresco & Xiaowei Zhan & John M. Shelton & Jeffrey A. SoRelle & Katie Keller & Danielle Renee Lazaro & Eva Marie Y. Moresco & Jin Huk Choi & Bruce , 2023. "OVOL2 sustains postnatal thymic epithelial cell identity," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    17. Yuki Matsushita & Angel Ka Yan Chu & Chiaki Tsutsumi-Arai & Shion Orikasa & Mizuki Nagata & Sunny Y. Wong & Joshua D. Welch & Wanida Ono & Noriaki Ono, 2022. "The fate of early perichondrial cells in developing bones," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    18. Alicia Villatoro & Vincent Cuminetti & Aurora Bernal & Carlos Torroja & Itziar Cossío & Alberto Benguría & Marc Ferré & Joanna Konieczny & Enrique Vázquez & Andrea Rubio & Peter Utnes & Almudena Tello, 2023. "Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation," Nature Communications, Nature, vol. 14(1), pages 1-28, December.
    19. Trent D. Hall & Hyunjin Kim & Mahmoud Dabbah & Jacquelyn A. Myers & Jeremy Chase Crawford & Antonio Morales-Hernandez & Claire E. Caprio & Pramika Sriram & Emilia Kooienga & Marta Derecka & Esther A. , 2022. "Murine fetal bone marrow does not support functional hematopoietic stem and progenitor cells until birth," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    20. Daniel C. Souza & Nicolas Hebert & Erica B. Esrick & M. Felicia Ciuculescu & Natasha M. Archer & Myriam Armant & Étienne Audureau & Christian Brendel & Giuseppe Caprio & Frédéric Galactéros & Donghui , 2023. "Genetic reversal of the globin switch concurrently modulates both fetal and sickle hemoglobin and reduces red cell sickling," Nature Communications, Nature, vol. 14(1), pages 1-10, 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:15:y:2024:i:1:d:10.1038_s41467-024-50054-0. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.