Cited by 84Mesenchymal stem cell researchHematopoietic Stem Cell TransplantationBone Tissue Engineering Materials

Effects of Severe Hypoxia on Bone Marrow Mesenchymal Stem Cells Differentiation Potential

Open access
Cicione, Claudia, Muiños-López, Emma, Hermida-Gómez, Tamara, Fuentes-Boquete, Isaac, Díaz-Prado, Silvia, Blanco, Francisco J.·2013·Stem Cells International

Abstract

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions.Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS).Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiation capacity in severe hypoxic cultures.Conclusions. In our experimental conditions, severe hypoxia affects the in vitro differentiation potential of BM-MSCs. Adipogenic, osteogenic, and chondrogenic differentiations are absent in severe hypoxic conditions. Our work underlines that severe hypoxia slows cell differentiation by means of molecular mechanisms since a decrease in the expression of adipocyte-, osteoblast-, and chondrocyte-specific genes was observed.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1155/2013/232896

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In neurological diseases, proteomic analysis revealed that hypoxia enhances the expression of proteins associated with neuroprotection, neural survival, differentiation, and axonal and neurite growth compared to the secretome obtained from normoxia-cultured MSCs.

    “proteomic analysis revealed that hypoxia enhances the expression of proteins [128], [129], [130] associated to neuroprotection, neural survival, differentiation, and axonal and neurite growth, when compared to the secretome obtained from normoxia-cultured MSCs [128].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [129]

    Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 52

  1. [1]Barlow S Brooke G Chatterjee K Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells Stem Cells and Development 2008 17 6 1095 1107 2-s2.0-57449102937 19006451
  2. [2]Hombach-Klonisch S Panigrahi S Rashedi I Adult stem cells and their trans-differentiation potential—perspectives and therapeutic applications Journal of Molecular Medicine 2008 86 12 1301 1314 2-s2.0-56949090024 18629466 PMC2954191
  3. [3]Minguell JJ Conget P Erices A Biology and clinical utilization of mesenchymal progenitor cells Brazilian Journal of Medical and Biological Research 2000 33 8 881 887 2-s2.0-0034244385 10920429
  4. [4]Pasquinelli G Tazzari P Ricci F Ultrastructural characteristics of human mesenchymal stromal (stem) cells derived from bone marrow and term placenta Ultrastructural Pathology 2007 31 1 23 31 2-s2.0-34147165019 17455095
  5. [5]Rydén M Dicker A Götherström C Functional characterization of human mesenchymal stem cell-derived adipocytes Biochemical and Biophysical Research Communications 2003 311 2 391 397 14592427
  6. [6]Muraglia A Cancedda R Quarto R Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model Journal of Cell Science 2000 113 7 1161 1166 2-s2.0-0034056758 10704367
  7. [7]Djouad F Bony C Häupl T Transcriptional profiles discriminate bone marrow-derived and synovium-derived mesenchymal stem cells Arthritis Research & Therapy 2005 7 6 R1304 R1315 2-s2.0-33644666806 16277684 PMC1297577
  8. [8]Sakaguchi Y Sekiya I Yagishita K Muneta T Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source Arthritis and Rheumatism 2005 52 8 2521 2529 2-s2.0-23644456193 16052568
  9. [9]Sato M Uchida K Nakajima H Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis Arthritis Research and Therapy 2012 14, article R31 2-s2.0-84856569681 PMC3392826 22314040
  10. [10]Pittenger MF Mesenchymal stem cells from adult bone marrow Methods in Molecular Biology 2008 449 27 44 2-s2.0-44649126719 18370081
  11. [11]Lasala GP Silva JA Kusnick BA Minguell JJ Combination stem cell therapy for the treatment of medically refractory coronary ischemia: A Phase I study Cardiovascular Revascularization Medicine 2011 12 1 29 34 2-s2.0-78651418001 21241969
  12. [12]Lee JS Hong JM Moon GJ A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke Stem Cells 2010 28 6 1099 1106 2-s2.0-77956638921 20506226
  13. [13]Satija NK Singh VK Verma YK Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine Journal of Cellular and Molecular Medicine 2009 13 11-12 4385 4402 2-s2.0-77951188870 19602034 PMC4515054
  14. [14]Talks KL Turley H Gatter KC The expression and distribution of the hypoxia-inducible factors HIF-1α and HIF-2α in normal human tissues, cancers, and tumor-associated macrophages American Journal of Pathology 2000 157 2 411 421 2-s2.0-0033870281 10934146 PMC1850121
  15. [16]Carrancio S López-Holgado N Sánchez-Guijo FM Optimization of mesenchymal stem cell expansion procedures by cell separation and culture conditions modification Experimental Hematology 2008 36 8 1014 1021 2-s2.0-47349086632 18468767
  16. [17]Kanichai M Ferguson D Prendergast PJ Campbell VA Hypoxia promotes chondrogenesis in rat mesenchymal stem cells: a role for AKT and hypoxia-inducible factor (HIF)-1α Journal of Cellular Physiology 2008 216 3 708 715 2-s2.0-48749086529 18366089
  17. [18]Koay EJ Athanasiou KA Hypoxic chondrogenic differentiation of human embryonic stem cells enhances cartilage protein synthesis and biomechanical functionality Osteoarthritis and Cartilage 2008 16 12 1450 1456 2-s2.0-55349109288 18541445
  18. [19]Grayson WL Zhao F Izadpanah R Bunnell B Ma T Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs Journal of Cellular Physiology 2006 207 2 331 339 2-s2.0-31744442047 16331674
  19. [20]Potier E Ferreira E Andriamanalijaona R Hypoxia affects mesenchymal stromal cell osteogenic differentiation and angiogenic factor expression Bone 2007 40 4 1078 1087 2-s2.0-33847713357 17276151
  20. [21]Dominici M Le Blanc K Mueller I Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement Cytotherapy 2006 8 4 315 317 2-s2.0-33747713246 16923606
  21. [22]Richler C Yaffe D The in vitro cultivation and differentiation capacities of myogenic cell lines Developmental Biology 1970 23 1 1 22 2-s2.0-0014841367 5481965
  22. [23]Johnstone B Hering TM Caplan AI Goldberg VM Yoo JU In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells Experimental Cell Research 1998 238 1 265 272 2-s2.0-0031817577 9457080
  23. [24]Livak KJ Schmittgen TD Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method Methods 2001 25 4 402 408 2-s2.0-0035710746 11846609
  24. [25]Sambrook J Fritsch EF Maniatis T Molecular Cloning: A Laboratory Manual 1989 2nd edition Cold Spring Harbor, NY, USA Cold Spring Harbor Laboratory Press
  25. [26]Hung S-P Ho JH Shih Y-RV Lo T Lee OK Hypoxia promotes proliferation and osteogenic differentiation potentials of human mesenchymal stem cells Journal of Orthopaedic Research 2012 30 2 260 266 2-s2.0-83855165785 21809383
  26. [27]Robins JC Akeno N Mukherjee A Hypoxia induces chondrocyte-specific gene expression in mesenchymal cells in association with transcriptional activation of Sox9 Bone 2005 37 3 313 322 2-s2.0-23844493183 16023419
  27. [28]Salim A Giaccia AJ Longaker MT Stem cell differentiation Nature Biotechnology 2004 22 804 805 15229534
  28. [29]Simon MC Keith B The role of oxygen availability in embryonic development and stem cell function Nature Reviews Molecular Cell Biology 2008 9 4 285 296 2-s2.0-41149115123 18285802 PMC2876333
  29. [30]Grant JL Smith B Bone marrow gas tensions, bone marrow blood flow, and erythropoiesis in man Annals of Internal Medicine 1963 58 801 809 2-s2.0-0001766243 13949863
  30. [32]Chow DC Wenning LA Miller WM Papoutsakis ET Modeling pO2 distributions in the bone marrow hematopoietic compartment. I. Krogh’s model Biophysical Journal 2001 81 675 684 11463616 PMC1301544
  31. [33]Chow DC Wenning LA Miller WM Papoutsakis ET Modeling pO2 distributions in the bone marrow hematopoietic compartment. II. Modified Kroghian models Biophysical Journal 2001 81 2 685 696 2-s2.0-0034907875 11463617 PMC1301545
  32. [34]Lavrentieva A Majore I Kasper C Hass R Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells Cell Communication and Signaling 2010 8, article 18 2-s2.0-77954562411 PMC2918620 20637101
  33. [35]Michiels C Minet E Mottet D Raes M Regulation of gene expression by oxygen: NF-κB and HIF-1, two extremes Free Radical Biology and Medicine 2002 33 9 1231 1242 2-s2.0-0036830469 12398931
  34. [36]Valorani MG Germani A Otto WR Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential Cell and Tissue Research 2010 341 1 111 120 2-s2.0-77954384101 20496083
  35. [37]van Oorschot AAM Smits AM Pardali E Doevendans PA Goumans M-J Low oxygen tension positively influences cardiomyocyte progenitor cell function Journal of Cellular and Molecular Medicine 2011 15 12 2723 2734 21306557 PMC4373441
  36. [38]Wang S Zhou Y Seavey CN Rapid and dynamic alterations of gene expression profiles of adult porcine bone marrow-derived stem cell in response to hypoxia Stem Cell Research 2010 4 2 117 128 2-s2.0-76749142384 20172499 PMC3763490
  37. [39]Lennon DP Edmison JM Caplan AI Cultivation of rat marrow-derived mesenchymal stem cells in reduced oxygen tension: effects on in vitro and in vivo osteochondrogenesis Journal of Cellular Physiology 2001 187 3 345 355 2-s2.0-0035028655 11319758
  38. [40]Parrinello S Samper E Krtolica A Goldstein J Melov S Campisi J Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts Nature Cell Biology 2003 5 8 741 747 2-s2.0-0042195820 12855956 PMC4940195
  39. [41]D’Ippolito G Diabira S Howard GA Roos BA Schiller PC Low oxygen tension inhibits osteogenic differentiation and enhances stemness of human MIAMI cells Bone 2006 39 3 513 522 2-s2.0-33646016858 16616713
  40. [42]Malladi P Xu Y Chiou M Giaccia AJ Longaker MT Effect of reduced oxygen tension on chondrogenesis and osteogenesis in adipose-derived mesenchymal cells American Journal of Physiology 2006 290 4 C1139 C1146 2-s2.0-33645125788 16291817
  41. [43]Schofield R The relationship between the spleen colony-forming cell and the haemopoietic stem cell Blood Cells 1978 4 1-2 7 25 2-s2.0-0018102359 747780
  42. [44]Ezashi T Das P Roberts RM Low O2 tensions and the prevention of differentiation of hES cells Proceedings of the National Academy of Sciences of the United States of America 2005 102 13 4783 4788 2-s2.0-16344380951 15772165 PMC554750
  43. [45]Genbacev O Miller RK Post-implantation differentiation and proliferation of cytotrophoblast cells: in vitro models—a review Placenta 2000 21 supplement A S45 S49 2-s2.0-10144219984 10831121
  44. [46]Fehrer C Brunauer R Laschober G Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan Aging Cell 2007 6 6 745 757 2-s2.0-36249020427 17925003
  45. [47]Fink T Abildtrup L Fogd K Induction of adipocyte-like phenotype in human mesenchymal stem cells by hypoxia Stem Cells 2004 22 7 1346 1355 2-s2.0-10444290010 15579652
  46. [48]Ren H Cao Y Zhao Q Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions Biochemical and Biophysical Research Communications 2006 347 1 12 21 16814746
  47. [49]Wang DW Fermor B Gimble JM Awad HA Guilak F Influence of oxygen on the proliferation and metabolism of adipose derived adult stem cells Journal of Cellular Physiology 2005 204 1 184 191 2-s2.0-20144385673 15754341
  48. [50]Semenza GL HIF-1, O2, and the 3 PHDs: how animal cells signal hypoxia to the nucleus Cell 2001 107 1 1 3 2-s2.0-0035812772 11595178
  49. [51]Mylotte LA Duffy AM Murphy M Metabolic flexibility permits mesenchymal stem cell survival in an ischemic environment Stem Cells 2008 26 5 1325 1336 2-s2.0-47949101704 18308942
  50. [52]Papandreou I Cairns RA Fontana L Lim AL Denko NC HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption Cell Metabolism 2006 3 3 187 197 2-s2.0-33644622570 16517406
  51. [53]dos Santos F Andrade PZ Boura JS Abecasis MM da Silva CL Cabral JMS Ex vivo expansion of human mesenchymal stem cells: a more effective cell proliferation kinetics and metabolism under hypoxia Journal of Cellular Physiology 2010 223 1 27 35 2-s2.0-75749145078 20020504
  52. [54]Ohnishi S Yasuda T Kitamura S Nagaya N Effect of hypoxia on gene expression of bone marrow-derived mesenchymal stem cells and mononuclear cells Stem Cells 2007 25 5 1166 1177 2-s2.0-34247619261 17289933

Cited by

Sorted by citations

Authors
Cicione, C., Muiños-López, E., Hermida-Gómez, T., Fuentes-Boquete, I., Díaz-Prado, S., & Blanco, F. J.
Affiliations
  • Universidade da Coruña (ES)
  • Rheumatology Division, INIBIC Hospital Universitario A Coruña, C/As Xubias S/N, 15006 A Coruña, Spain
  • CIBER-BBN-Cellular Therapy Area, Hospital Universitario A Coruña, C/As Xubias S/N, 15006 A Coruña, Spain
Corresponding author
Blanco, Francisco J.
Venue
Stem Cells International
Published
2013
Volume
2013
Pages
1-11
ISSN
  • 1687-966X (ISSN-L)
  • 1687-9678
OpenAlex
W2071227792
Cited by
84
References
2
Citations by year
2025: 2 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 7 · 2017: 8 · 2016: 17 · 2015: 5 · 2014: 6
FWCI
4.60
Type
journal article
Language
en
Open access
Locations
  • Stem Cells International (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Hispana (submittedVersion, cc-by)
  • Repositorio institucional da Universidade de Santiago de Compostela (University of Santiago de Compostela) (submittedVersion, other-oa)
  • RUC (Universidade Da Coruña) (submittedVersion, cc-by)
  • RUNA. Repositorio Institucional del Sergas (Servicio Gallego de Salud (SERGAS)) (submittedVersion, cc-by)
Funders
  • Xunta de Galicia (PS07/84, CB06-01-0040, PLE2009-0144, 08/2028)
  • Universidade da Coruña and Instituto de Salud Carlos (PS07/84, CB06-01-0040, PLE2009-0144, 08/2028)
  • Ministerio Ciencia e Innovacion (PS07/84, CB06-01-0040, PLE2009-0144, 08/2028)
  • Fondo Investigacion Sanitaria-PI (PS07/84, CB06-01-0040, PLE2009-0144, 08/2028)
  • Fondo de Investigación Sanitaria (PS07/84, CB06-01-0040, PLE2009-0144, 08/2028)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
Keywords
bone marrow mesenchymal stem cells, severe hypoxia, stem cell differentiation, adipogenesis, osteogenic differentiation, chondrogenic differentiation, lineage-specific gene expression, normoxia, cell therapy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review