PMID- 22268587
OWN - NLM
STAT- MEDLINE
DCOM- 20120522
LR  - 20220321
IS  - 1600-0609 (Electronic)
IS  - 0902-4441 (Linking)
VI  - 88
IP  - 5
DP  - 2012 May
TI  - Hypoxia improves expansion potential of human cord blood-derived hematopoietic 
      stem cells and marrow repopulation efficiency.
PG  - 396-405
LID - 10.1111/j.1600-0609.2012.01759.x [doi]
AB  - OBJECTIVES: In bone marrow, hematopoietic stem cells (HSCs) reside in the most 
      hypoxic endosteum niche, whereas the proliferating progenitors are located near 
      the relatively oxygen-rich vascular region. High oxygen tension is potentially 
      detrimental to HSCs. The objective of this investigation was to compare cellular, 
      functional, and molecular responses of human umbilical cord blood (UCB)-derived 
      hematopoietic stem and progenitor cells in culture under hypoxic and normoxic 
      conditions. METHODS: CD133-enriched UCB cells were cultured in growth factor 
      containing serum-free and serum-supplemented medium under 5% O(2) (hypoxia) or 
      21% O(2) (normoxia) for 10 d. The phenotypes of expanded cells were analyzed by 
      flow cytometry and the engraftability by SCID-repopulation assay. The expression 
      of hypoxia-inducible factor (HIF)-1alpha and some of its target genes was analyzed by 
      real-time RT-PCR. RESULTS: In hypoxic culture, CD34(+) CD38(-) cells were 
      expanded about 27-fold, which was significantly (P < 0.01) higher than that 
      obtained in normoxic culture. Serum-free culture did not support the growth of 
      cells in the presence of 21% O(2) . Myeloid colony-forming potential of cells was 
      significantly (P < 0.05) increased in 5% O(2) compared with 21% O(2) culture. 
      SCID-repopulation efficiency seems to be better preserved in the cells cultured 
      under hypoxic conditions. Hypoxia significantly (P < 0.05) induced the expression 
      of HIF-1alpha, vascular endothelial growth factor (VEGF), and ABCG2 genes and also 
      upregulated CXCR4 receptor expression. CONCLUSIONS: Low oxygen tension enhanced 
      the proliferation of UCB-derived HSC/progenitor cells and maintenance of 
      SCID-repopulating cells than normoxia. These expanded cells are expected to be 
      beneficial in the patients who lack human leukocyte antigen (HLA)-matched donors.
CI  - (c) 2012 John Wiley & Sons A/S.
FAU - Roy, Sushmita
AU  - Roy S
AD  - Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali 
      Marg, New Delhi, India.
FAU - Tripathy, Manjul
AU  - Tripathy M
FAU - Mathur, Nitin
AU  - Mathur N
FAU - Jain, Asish
AU  - Jain A
FAU - Mukhopadhyay, Asok
AU  - Mukhopadhyay A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120217
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 0 (ABCG2 protein, human)
RN  - 0 (AC133 Antigen)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Antigens, CD)
RN  - 0 (Culture Media)
RN  - 0 (Glycoproteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PROM1 protein, human)
RN  - 0 (Peptides)
RN  - 0 (Prom1 protein, mouse)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - AC133 Antigen
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2
MH  - ATP-Binding Cassette Transporters/metabolism
MH  - Animals
MH  - Antigens, CD/immunology
MH  - Apoptosis
MH  - Cell Division
MH  - *Cell Hypoxia
MH  - Cell Lineage
MH  - Cell Proliferation
MH  - Culture Media
MH  - Fetal Blood/*cytology
MH  - Flow Cytometry
MH  - Glycoproteins/immunology
MH  - Hematopoietic Stem Cells/*cytology/immunology
MH  - Humans
MH  - Mice
MH  - Mice, SCID
MH  - Neoplasm Proteins/metabolism
MH  - Peptides/immunology
MH  - Real-Time Polymerase Chain Reaction
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2012/01/25 06:00
MHDA- 2012/05/23 06:00
CRDT- 2012/01/25 06:00
PHST- 2012/01/25 06:00 [entrez]
PHST- 2012/01/25 06:00 [pubmed]
PHST- 2012/05/23 06:00 [medline]
AID - 10.1111/j.1600-0609.2012.01759.x [doi]
PST - ppublish
SO  - Eur J Haematol. 2012 May;88(5):396-405. doi: 10.1111/j.1600-0609.2012.01759.x. 
      Epub 2012 Feb 17.