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

Hematopoietic Stem Cells / metabolism Animals Nestin / metabolism Extracellular Matrix / metabolism Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Mice Stem Cell Niche Hydrogels / chemistry Bioengineering / methods Humans Mesenchymal Stem Cells / metabolism Hematopoietic Stem Cell Transplantation Antigens, CD34 / metabolism Collagen Type I / metabolism Cell Differentiation Mice, Inbred C57BL

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
10 Jul 2024
Historique:
received: 09 08 2022
accepted: 27 06 2024
medline: 11 7 2024
pubmed: 11 7 2024
entrez: 10 7 2024
Statut: epublish

Résumé

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

Identifiants

DOI: 10.1038/s41467-024-50054-0 PMID: 38987295
pubmed: 38987295
doi: 10.1038/s41467-024-50054-0
pii: 10.1038/s41467-024-50054-0
doi:

Substances chimiques

Nestin 0
Hypoxia-Inducible Factor 1, alpha Subunit 0
Hydrogels 0
Antigens, CD34 0
Collagen Type I 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5791

Subventions

Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/N018419/1
Organisme : RCUK | Engineering and Physical Sciences Research Council (EPSRC)
ID : EP/P001114/1
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/R005567/1

Informations de copyright

© 2024. The Author(s).

Références

Burns, R., Leal, J., Sullivan, R. & Luengo-Fernandez, R. Economic burden of malignant blood disorders across Europe: a population-based cost analysis. Lancet Haematol. 3, e362–e370 (2016).
pubmed: 27476787 doi: 10.1016/S2352-3026(16)30062-X
Granot, N. & Storb, R. History of hematopoietic cell transplantation: challenges and progress. Haematologica 105, 2716–2729 (2020).
pubmed: 33054108 pmcid: 7716373 doi: 10.3324/haematol.2019.245688
State of the Registry 2020–2021. In: Anthony Nolan NHS Stem Cell Registry Annual Review 1–10 https://www.anthonynolan.org/sites/default/files/2022-06/State%20of%20The%20Registry%202020-2021.pdf (2022).
Zon, L. I. Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal. Nature 453, 306–313 (2008).
pubmed: 18480811 doi: 10.1038/nature07038
Yang, L. et al. Identification of Lin-Sca1+kit+CD34 +Flt3- short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients. Blood 105, 2717–2723 (2005).
pubmed: 15572596 doi: 10.1182/blood-2004-06-2159
Dexter, T., Moore, M. A. & Sheridan, A. P. Maintenance of hemopoietic stem cells and production of differentiated progeny in allogeneic and semiallogeneic bone marrow chimeras in vitro. J. Exp. Med. 145, 1612–1616 (1977).
pubmed: 325171 doi: 10.1084/jem.145.6.1612
Nakauchi, H., Sudo, K. & Hideo, E. M. A. Quantitative assessment of the stem cell self-renewal capacity. Ann. N. Y. Acad. Sci. 938, 18–25 (2001).
pubmed: 11458506 doi: 10.1111/j.1749-6632.2001.tb03570.x
Li, J. et al. Development and clinical advancement of small molecules for ex vivo expansion of hematopoietic stem cell. Acta Pharm. Sin. B 12, 2808–2831 (2021).
pubmed: 35755294 pmcid: 9214065 doi: 10.1016/j.apsb.2021.12.006
Fares, I. et al. EPCR expression marks UM171-expanded CD34+ cord blood stem cells. Blood 129, 3344–3351 (2017).
pubmed: 28408459 doi: 10.1182/blood-2016-11-750729
Wagner, J. E. et al. Phase I/II trial of stemregenin-1 expanded umbilical cord blood hematopoietic stem cells supports testing as a stand-alone graft. Cell Stem Cell 18, 144–155 (2016).
pubmed: 26669897 doi: 10.1016/j.stem.2015.10.004
Pinho, S. & Frenette, P. S. Haematopoietic stem cell activity and interactions with the niche. Nat. Rev. Mol. Cell Biol. https://doi.org/10.1038/s41580-019-0103-9 (2019).
Méndez-Ferrer, S. et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466, 829–834 (2010).
pubmed: 20703299 pmcid: 3146551 doi: 10.1038/nature09262
Kunisaki, Y. et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature 502, 637–643 (2013).
pubmed: 24107994 pmcid: 3821873 doi: 10.1038/nature12612
Ding, L. & Morrison, S. J. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature 495, 231–235 (2013).
pubmed: 23434755 pmcid: 3600153 doi: 10.1038/nature11885
Sacchetti, B. et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131, 324–336 (2007).
pubmed: 17956733 doi: 10.1016/j.cell.2007.08.025
Crisan, M. et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3, 301–313 (2008).
pubmed: 18786417 doi: 10.1016/j.stem.2008.07.003
Sugiyama, T., Kohara, H., Noda, M. & Nagasawa, T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25, 977–988 (2006).
pubmed: 17174120 doi: 10.1016/j.immuni.2006.10.016
Pinho, S. et al. PDGFR A and CD51 mark human stem cells capable of hematopoietic progenitor cell expansion. J. Exp. Med. 210, 1351–1367 (2013).
pubmed: 23776077 pmcid: 3698522 doi: 10.1084/jem.20122252
Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).
pubmed: 16923388 doi: 10.1016/j.cell.2006.06.044
Chen, X. et al. Mechanical heterogeneity in the bone microenvironment as characterized by atomic force microscopy. Biophys. J. 119, 502–513 (2020).
pubmed: 32668233 pmcid: 7401034 doi: 10.1016/j.bpj.2020.06.026
Calvi, L. M. et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425, 841–846 (2003).
pubmed: 14574413 doi: 10.1038/nature02040
Shen, B. et al. A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis. Nature 591, 438–444 (2021).
Salmerón-Sánchez, M. & Dalby, M. J. Synergistic growth factor microenvironments. Chem. Commun. 52, 13327–13336 (2016).
doi: 10.1039/C6CC06888J
Spencer, J. A. et al. Direct measurement of local oxygen concentration in the bone marrow of live animals. Nature 508, 269–273 (2014).
pubmed: 24590072 pmcid: 3984353 doi: 10.1038/nature13034
Estrada, J. C. et al. Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis. Cell Death Differ. 19, 743–755 (2012).
pubmed: 22139129 doi: 10.1038/cdd.2011.172
Guarnerio, J. et al. Bone marrow endosteal mesenchymal progenitors depend on HIF factors for maintenance and regulation of hematopoiesis. Stem Cell Rep. 2, 794–809 (2014).
doi: 10.1016/j.stemcr.2014.04.002
Nakahara, F. et al. Engineering a haematopoietic stem cell niche by revitalizing mesenchymal stromal cells. Nat. Cell Biol. 21, 560–567 (2019).
pubmed: 30988422 pmcid: 6499646 doi: 10.1038/s41556-019-0308-3
Leisten, I. et al. 3D co-culture of hematopoietic stem and progenitor cells and mesenchymal stem cells in collagen scaffolds as a model of the hematopoietic niche. Biomaterials 33, 1736–1747 (2012).
pubmed: 22136713 doi: 10.1016/j.biomaterials.2011.11.034
Gilchrist, A. E. & Harley, B. A. C. Connecting secretome to hematopoietic stem cell phenotype shifts in an engineered bone marrow niche. Integr. Biol. 12, 175–187 (2020).
doi: 10.1093/intbio/zyaa013
Bourgine, P. E. et al. In vitro biomimetic engineering of a human hematopoietic niche with functional properties. Proc. Natl. Acad. Sci. 115, E5688–E5695 (2018).
pubmed: 29866839 pmcid: 6016789 doi: 10.1073/pnas.1805440115
Rödling, L. et al. 3D models of the hematopoietic stem cell niche under steady-state and active conditions. Sci. Rep. 1–15 https://doi.org/10.1038/s41598-017-04808-0 (2017).
Chou, D. B. et al. On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology. Nat. Biomed. Eng. 4, 394–406 (2020).
Doulatov, S., Notta, F., Laurenti, E. & Dick, J. E. Hematopoiesis: a human perspective. Cell Stem Cell 10, 120–136 (2012).
pubmed: 22305562 doi: 10.1016/j.stem.2012.01.006
Klamer, S. & Voermans, C. The role of novel and known extracellular matrix and adhesion molecules in the homeostatic and regenerative bone marrow microenvironment. Cell Adh. Migr. 8, 563–577 (2014).
pubmed: 25482635 pmcid: 4594522 doi: 10.4161/19336918.2014.968501
Llopis-hernández, V. et al. Material-driven fibronectin assembly for high-efficiency presentation of growth factors. Sci. Adv. 1–11 https://doi.org/10.1126/sciadv.1600188 (2016).
Cheng, Z. A. et al. Nanoscale coatings for ultralow dose BMP-2-driven regeneration of critical-sized bone defects. Adv. Sci. 6, 1800361 (2018).
doi: 10.1002/advs.201800361
Itkin, T. et al. Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature 1–19 https://doi.org/10.1038/nature17624 (2016).
Asada, N. et al. Differential cytokine contributions of perivascular haematopoietic stem cell niches. https://doi.org/10.1038/ncb3475 (2017).
Nilsson, S. K. et al. Immunofluorescence characterization of key extracellular matrix proteins in murine bone marrow in situ. J. Histochem. Cytochem. 46, 371–377 (1998).
pubmed: 9487119 doi: 10.1177/002215549804600311
Choi, J. S. & Harley, B. A. C. Marrow-inspired matrix cues rapidly affect early fate decisions of hematopoietic stem and progenitor cells. Sci. Adv. 3, e1600455 (2017).
pubmed: 28070554 pmcid: 5218514 doi: 10.1126/sciadv.1600455
Früh, S. M., Schoen, I., Ries, J. & Vogel, V. Molecular architecture of native fibronectin fibrils. Nat. Commun. 6, 7275 (2015).
pubmed: 26041410 doi: 10.1038/ncomms8275
Klotzsch, E. et al. Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites. Proc. Natl. Acad. Sci. USA 106, 18267–18272 (2009).
pubmed: 19826086 pmcid: 2761242 doi: 10.1073/pnas.0907518106
Bieniek, M., Llopis-Hernandez, V., Douglas, K., Salmeron-Sanchez, M. & Lorenz, C. Minor chemistry changes alter surface hydration to control fibronectin adsorption and assembly into nanofibrils. Adv. Theory Simul. 1900169, 1–13 (2019).
Martino, M. M. & Hubbell, J. A. The 12th-14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain. FASEB J. 24, 4711–4721 (2010).
pubmed: 20671107
Park, D. et al. Nestin is required for the proper self-renewal of neural stem cells. Stem Cells 28, 2162–2171 (2010).
pubmed: 20963821 doi: 10.1002/stem.541
Coutu, D. L., Kokkaliaris, K. D., Kunz, L. & Schroeder, T. Three-dimensional map of nonhematopoietic bone and bone-marrow cells and molecules. Nat. Biotechnol. 35, 1202–1210 (2017).
pubmed: 29131149 doi: 10.1038/nbt.4006
Le Blanc, K. & Mougiakakos, D. Multipotent mesenchymal stromal cells and the innate immune system. Nat. Rev. Immunol. 12, 383–396 (2012).
pubmed: 22531326 doi: 10.1038/nri3209
Dorronsoro, A. et al. Intracellular role of IL-6 in mesenchymal stromal cell immunosuppression and proliferation. Sci. Rep. 10, 1–12 (2020).
doi: 10.1038/s41598-020-78864-4
Haghighitalab, A. et al. Investigating the effects of IDO1, PTGS2, and TGF-β1 overexpression on immunomodulatory properties of hTERT-MSCs and their extracellular vesicles. Sci. Rep. 11, 1–19 (2021).
doi: 10.1038/s41598-021-87153-7
He, Y. et al. Mesenchymal stem cell deficiency influences megakaryocytopoiesis through the TNFAIP3/NF-κB/SMAD pathway in patients with immune thrombocytopenia. Br. J. Haematol. 180, 395–411 (2018).
pubmed: 29327472 doi: 10.1111/bjh.15034
Shen, S. P. et al. EphA2 is a biomarker of hMSCs derived from human placenta and umbilical cord. Taiwan. J. Obstet. Gynecol. 54, 749–756 (2015).
pubmed: 26700997 doi: 10.1016/j.tjog.2015.10.012
Weidemann, A. & Johnson, R. S. Biology of HIF-1 a. Cell Death Differ. 15, 621–627 (2008).
pubmed: 18259201 doi: 10.1038/cdd.2008.12
Pattappa, G., Heywood, H. K., de Bruijn, J. D. & Lee, D. A. The metabolism of human mesenchymal stem cells during proliferation and differentiation. J. Cell. Physiol. 226, 2562–2570 (2011).
pubmed: 21792913 doi: 10.1002/jcp.22605
Vander Heiden, M. G., Cantley, L. C. & Thompson, C. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029–1033 (2009).
doi: 10.1126/science.1160809
Sahlgren, C. M. et al. Cdk5 regulates the organization of Nestin and its association with p35. Mol. Cell. Biol. 23, 5090–5106 (2003).
pubmed: 12832492 pmcid: 162223 doi: 10.1128/MCB.23.14.5090-5106.2003
Pallari, H.-M. et al. Nestin as a regulator of Cdk5 in differentiating myoblasts. Mol. Biol. Cell 22, 1539–1549 (2011).
pubmed: 21346193 pmcid: 3084676 doi: 10.1091/mbc.e10-07-0568
Sahlgren, C. M. et al. A nestin scaffold links Cdk5/p35 signaling to oxidant-induced cell death. EMBO J. 25, 4808–4819 (2006).
pubmed: 17036052 pmcid: 1618100 doi: 10.1038/sj.emboj.7601366
Galleu, A. et al. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci. Transl. Med. 9, 1–12 (2017).
doi: 10.1126/scitranslmed.aam7828
Shentu, Y. et al. Nestin promotes peritoneal fibrosis by protecting HIF1-α from proteasomal degradation. Front. Physiol. 11, 1–11 (2020).
doi: 10.3389/fphys.2020.517912
Van Galen, P. et al. Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion. Cell Stem Cell 14, 94–106 (2014).
pubmed: 24388174 doi: 10.1016/j.stem.2013.11.021
Wu, Y. et al. Highly efficient therapeutic gene editing of human hematopoietic stem cells. Nat. Med. 25, 776–783 (2019).
pubmed: 30911135 pmcid: 6512986 doi: 10.1038/s41591-019-0401-y
Grassinger, J., Haylock, D. N., Williams, B., Olsen, G. H. & Nilsson, S. K. Phenotypically identical hemopoietic stem cells isolated from different regions of bone marrow have different biologic potential. Blood 116, 3185–3196 (2010).
pubmed: 20631378 doi: 10.1182/blood-2009-12-260703
Ross, E. A. et al. Nanotopography reveals metabolites that maintain the immunosuppressive phenotype of mesenchymal stem cells. Nat. Commun. 14, 753 (2023).
pubmed: 36765065 pmcid: 9918539 doi: 10.1038/s41467-023-36293-7
Wilson, A. et al. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell 135, 1118–1129 (2008).
pubmed: 19062086 doi: 10.1016/j.cell.2008.10.048
Crippa, S. et al. Erratum: mesenchymal stromal cells improve the transplantation outcome of CRISPR-Cas9 gene-edited human HSPCs (Molecular Therapy, (S1525001622004993), (10.1016/j.ymthe.2022.08.011)). Mol. Ther. 30, 3333 (2022).
pubmed: 36096132 pmcid: 9552814 doi: 10.1016/j.ymthe.2022.09.005
Chaudhuri, O. et al. Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat. Mater. https://doi.org/10.1038/nmat4489 (2015).
Kaufmann, K. B. et al. A latent subset of human hematopoietic stem cells resists regenerative stress to preserve stemness. Nat. Immunol. 22, 723–734 (2021).
pubmed: 33958784 doi: 10.1038/s41590-021-00925-1
García-Prat, L. et al. TFEB-mediated endolysosomal activity controls human hematopoietic stem cell fate. Cell Stem Cell 28, 1838–1850.e10 (2021).
pubmed: 34343492 doi: 10.1016/j.stem.2021.07.003
Napolitano, G. & Ballabio, A. TFEB at a glance. J. Cell Sci. 129, 2475–2481 (2016).
pubmed: 27252382 pmcid: 4958300 doi: 10.1242/jcs.146365
Hsu, C. C. et al. Biophysical regulations of epigenetic state and notch signaling in neural development using microgroove substrates. ACS Appl. Mater. Interfaces https://doi.org/10.1021/acsami.2c01996 (2022).
Tajik, A. et al. Transcription upregulation via force-induced direct stretching of chromatin. Nat. Mater. 15, 1287–1296 (2016).
pubmed: 27548707 pmcid: 5121013 doi: 10.1038/nmat4729
Caiazzo, M. et al. Defined three-dimensional microenvironments boost induction of pluripotency. Nat. Mater. 15, 344–352 (2016).
pubmed: 26752655 doi: 10.1038/nmat4536
Nemec, S. & Kilian, K. A. Materials control of the epigenetics underlying cell plasticity. Nat. Rev. Mater. https://doi.org/10.1038/s41578-020-00238-z (2020).
Takayama, N. et al. The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization. Cell Stem Cell 28, 488–501.e10 (2021).
pubmed: 33242413 doi: 10.1016/j.stem.2020.11.001
Nakagawa, R., Soh, J. W. & Michie, A. M. Subversion of protein kinase Cα signaling in hematopoietic progenitor cells results in the generation of a B-cell chronic lymphocytic leukemia-like population in vivo. Cancer Res. 66, 527–534 (2006).
pubmed: 16397269 doi: 10.1158/0008-5472.CAN-05-0841
Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet. J. 17, 10 (2011).
doi: 10.14806/ej.17.1.200
Bray, N. L., Pimentel, H., Melsted, P. & Pachter, L. Near-optimal probabilistic RNA-seq quantification. Nat. Biotechnol. 34, 525–527 (2016).
pubmed: 27043002 doi: 10.1038/nbt.3519
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 1–21 (2014).
doi: 10.1186/s13059-014-0550-8
Westrop, G. D. et al. Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine. PLoS One 12, e0189072 (2017).
pubmed: 29267346 pmcid: 5739422 doi: 10.1371/journal.pone.0189072
Chokkathukalam, A. et al. MzMatch-ISO: An R tool for the annotation and relative quantification of isotope-labelled mass spectrometry data. Bioinformatics 29, 281–283 (2013).
pubmed: 23162054 doi: 10.1093/bioinformatics/bts674
Miller, P. H. et al. Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors. Blood 121, 3–6 (2013).
doi: 10.1182/blood-2012-09-456566
Brinkman, E. K., Chen, T., Amendola, M. & Van Steensel, B. Easy quantitative assessment of genome editing by sequence trace decomposition. Nucleic Acids Res. 42, 1–8 (2014).
doi: 10.1093/nar/gku936
Xiao, Y. et al. Current insights into the bone marrow niche: from biology in vivo to bioengineering ex vivo. Biomaterials 286, 121568 (2022).
pubmed: 35580474 doi: 10.1016/j.biomaterials.2022.121568

Auteurs

Hannah Donnelly (H)

Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom.
ORCID: 0000-0002-5154-9971

Ewan Ross (E)

Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom.

Yinbo Xiao (Y)

Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom.

Rio Hermantara (R)

School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, G61 1QH, United Kingdom.
ORCID: 0000-0002-0555-637X

Aqeel F Taqi (AF)

School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, G61 1QH, United Kingdom.

W Sebastian Doherty-Boyd (WS)

Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom.
ORCID: 0009-0002-4831-7480

Jennifer Cassels (J)

School of Cancer Sciences, Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, University of Glasgow, Glasgow, G12 0YN, United Kingdom.

Penelope M Tsimbouri (PM)

Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom.
ORCID: 0000-0001-5124-7458

Karen M Dunn (KM)

School of Cancer Sciences, Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, University of Glasgow, Glasgow, G12 0YN, United Kingdom.
ORCID: 0000-0002-6532-970X

Jodie Hay (J)

School of Cancer Sciences, Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, University of Glasgow, Glasgow, G12 0YN, United Kingdom.
ORCID: 0000-0002-2000-2578

Annie Cheng (A)

Centre for the Cellular Microenvironment, Division of Biomedical Engineering, James Watt School of Engineering, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom.

R M Dominic Meek (RMD)

Department of Trauma and Orthopaedics, Queen Elizabeth University Hospital, Glasgow, G51 4TF, United Kingdom.

Nikhil Jain (N)

Institute of Inflammation and Ageing, University of Birmingham, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom.

Christopher West (C)

MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, EH16 4UU, United Kingdom.

Helen Wheadon (H)

School of Cancer Sciences, Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, University of Glasgow, Glasgow, G12 0YN, United Kingdom.
ORCID: 0000-0001-9902-3170

Alison M Michie (AM)

School of Cancer Sciences, Paul O'Gorman Leukaemia Research Centre, Gartnavel General Hospital, University of Glasgow, Glasgow, G12 0YN, United Kingdom.
ORCID: 0000-0002-5404-475X

Bruno Peault (B)

MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, EH16 4UU, United Kingdom.

Adam G West (AG)

School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, G61 1QH, United Kingdom.

Manuel Salmeron-Sanchez (M)

Centre for the Cellular Microenvironment, Division of Biomedical Engineering, James Watt School of Engineering, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom. manuel.salmeron-sanchez@glasgow.ac.uk.
ORCID: 0000-0002-8112-2100

Matthew J Dalby (MJ)

Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom. matthew.dalby@glasgow.ac.uk.
ORCID: 0000-0002-0528-3359

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Cellules souches hématopoïétiques › Bioengineered niches that recreate...
questionsmedicales.fr › Eucaryotes › Animaux › Bioengineered niches that recreate...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Nestine › Bioengineered niches that recreate...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace extracellulaire › Matrice extracellulaire › Bioengineered niches that recreate...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique hélice-boucle-hélice › Facteur-1 induit par l'hypoxie › Sous-unité alpha du facteur-1 induit par l'hypoxie › Bioengineered niches that recreate...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Bioengineered niches that recreate...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Niche de cellules souches › Bioengineered niches that recreate...
questionsmedicales.fr › Préparations pharmaceutiques › Colloïdes › Gels › Hydrogels › Bioengineered niches that recreate...
questionsmedicales.fr › Technologie, industrie et agriculture › Ingénierie › Bioingénierie › Bioengineered niches that recreate...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Bioengineered niches that recreate...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches multipotentes › Cellules souches mésenchymateuses › Bioengineered niches that recreate...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › Transplantation de cellules souches hématopoïétiques › Bioengineered niches that recreate...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes CD › Antigènes CD34 › Bioengineered niches that recreate...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Collagène › Collagènes fibrillaires › Collagène de type I › Bioengineered niches that recreate...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Bioengineered niches that recreate...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Bioengineered niches that recreate...