PMID- 27717376
OWN - NLM
STAT- MEDLINE
DCOM- 20171113
LR  - 20181202
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 7
IP  - 1
DP  - 2016 Oct 7
TI  - Rapid and efficient generation of neural progenitors from adult bone marrow 
      stromal cells by hypoxic preconditioning.
PG  - 146
LID - 146
AB  - BACKGROUND: Bone marrow stromal cells (BMSCs) are attractive as a source of 
      neural progenitors for ex vivo generation of neurons and glia. Limited numbers of 
      this subpopulation, however, hinder translation into autologous cell-based 
      therapy. Here, we demonstrate rapid and efficient conditioning with hypoxia to 
      enrich for these neural progenitor cells prior to further expansion in 
      neurosphere culture. METHOD: Adherent cultures of BMSCs (rat/human) were 
      subjected to 1 % oxygen for 24 h and then subcultured as neurospheres with 
      epidermal growth factor (EGF) and basic fibroblast growth factor supplementation. 
      Neurospheres and cell progeny were monitored immunocytochemically for marker 
      expression. To generate Schwann cell-like cells, neurospheres were plated out and 
      exposed to gliogenic medium. The resulting cells were co-cultured with purified 
      dorsal root ganglia (rat) neurons and then tested for commitment to the Schwann 
      cell fate. Fate-committed Schwann cells were subjected to in vitro myelination 
      assay. RESULTS: Transient hypoxic treatment increased the size and number of 
      neurospheres generated from both rat and human BMSCs. This effect was 
      EGF-dependent and attenuated with the EGF receptor inhibitor erlotinib. Hypoxia 
      did not affect the capacity of neurospheres to generate neuron- or glia-like 
      precursors. Human Schwann cell-like cells generated from hypoxia-treated BMSCs 
      demonstrated expression of S100beta /p75 and capacity for myelination in vitro. 
      CONCLUSION: Enhancing the yield of neural progenitor cells with hypoxic 
      preconditioning of BMSCs in vitro but without inherent risks of genetic 
      manipulation provides a platform for upscaling production of neural cell 
      derivatives for clinical application in cell-based therapy.
FAU - Mung, Kwan-Long
AU  - Mung KL
AD  - Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The 
      University of Hong Kong, Pokfulam, Hong Kong.
AD  - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, Pokfulam, Hong Kong.
FAU - Tsui, Yat-Ping
AU  - Tsui YP
AD  - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, Pokfulam, Hong Kong.
FAU - Tai, Evelyn Wing-Yin
AU  - Tai EW
AD  - Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The 
      University of Hong Kong, Pokfulam, Hong Kong.
AD  - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, Pokfulam, Hong Kong.
FAU - Chan, Ying-Shing
AU  - Chan YS
AD  - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, Pokfulam, Hong Kong.
FAU - Shum, Daisy Kwok-Yan
AU  - Shum DK
AD  - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of 
      Hong Kong, Pokfulam, Hong Kong.
FAU - Shea, Graham Ka-Hon
AU  - Shea GK
AD  - Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The 
      University of Hong Kong, Pokfulam, Hong Kong. gkshea@hku.hk.
AD  - General Office, 5/F, Professorial Block, Queen Mary Hospital, Pokfulam, Hong 
      Kong. gkshea@hku.hk.
LA  - eng
PT  - Journal Article
DEP - 20161007
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
SB  - IM
MH  - Animals
MH  - Cell Culture Techniques/methods
MH  - Cell Differentiation/physiology
MH  - Cells, Cultured
MH  - Coculture Techniques/methods
MH  - Fibroblast Growth Factor 2/metabolism
MH  - Ganglia, Spinal/cytology/metabolism
MH  - Humans
MH  - Hypoxia/*physiopathology
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Neural Stem Cells/*cytology/metabolism
MH  - Neurogenesis/physiology
MH  - Neuroglia/cytology/metabolism
MH  - Neurons/*cytology/metabolism
MH  - Rats
MH  - Schwann Cells/cytology/metabolism
MH  - Stem Cells/*cytology/metabolism
PMC - PMC5055711
OTO - NOTNLM
OT  - Bone marrow stromal cell
OT  - Hypoxia
OT  - Neural progenitor cell
OT  - Schwann cell
OT  - Stem cell niche
EDAT- 2016/10/09 06:00
MHDA- 2017/11/14 06:00
PMCR- 2016/10/07
CRDT- 2016/10/09 06:00
PHST- 2016/06/30 00:00 [received]
PHST- 2016/09/06 00:00 [accepted]
PHST- 2016/08/25 00:00 [revised]
PHST- 2016/10/09 06:00 [entrez]
PHST- 2016/10/09 06:00 [pubmed]
PHST- 2017/11/14 06:00 [medline]
PHST- 2016/10/07 00:00 [pmc-release]
AID - 10.1186/s13287-016-0409-x [pii]
AID - 409 [pii]
AID - 10.1186/s13287-016-0409-x [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2016 Oct 7;7(1):146. doi: 10.1186/s13287-016-0409-x.