PMID- 25383184
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141112
LR  - 20181113
IS  - 2046-1402 (Print)
IS  - 2046-1402 (Electronic)
IS  - 2046-1402 (Linking)
VI  - 3
DP  - 2014
TI  - Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats 
      with focal ischemia.
PG  - 131
LID - 10.12688/f1000research.4219.2 [doi]
LID - 131
AB  - The pursuit of targeting multiple pathways in the ischemic cascade of cerebral 
      stroke is a promising treatment option. We examined the regenerative potential of 
      conditioned medium derived from rat and human apoptotic mononuclear cells (MNC), 
      rMNC (apo sec) and hMNC (apo sec), in experimental stroke. We performed middle 
      cerebral artery occlusion on Wistar rats and administered apoptotic 
      MNC-secretomes intraperitoneally in two experimental settings. Ischemic lesion 
      volumes were determined 48 hours after cerebral ischemia. Neurological 
      evaluations were performed after 6, 24 and 48 hours. Immunoblots were conducted 
      to analyze neuroprotective signal-transduction in human primary glia cells and 
      neurons. Neuronal sprouting assays were performed and neurotrophic factors in 
      both hMNC (apo sec) and rat plasma were quantified using ELISA. Administration of 
      rat as well as human apoptotic MNC-secretomes significantly reduced ischemic 
      lesion volumes by 36% and 37%, respectively. Neurological examinations revealed 
      improvement after stroke in both treatment groups. Co-incubation of human 
      astrocytes, Schwann cells and neurons with hMNC (apo sec) resulted in activation 
      of several signaling cascades associated with the regulation of cytoprotective 
      gene products and enhanced neuronal sprouting in vitro. Analysis of neurotrophic 
      factors in hMNC (apo sec) and rat plasma revealed high levels of brain derived 
      neurotrophic factor (BDNF). Our data indicate that apoptotic MNC-secretomes 
      elicit neuroprotective effects on rats that have undergone ischemic stroke.
FAU - Altmann, Patrick
AU  - Altmann P
AD  - Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, 
      Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and 
      Regeneration, Vienna, 1090, Austria.
FAU - Mildner, Michael
AU  - Mildner M
AD  - Department of Dermatology, Medical University of Vienna, Vienna, 1090, Austria.
FAU - Haider, Thomas
AU  - Haider T
AD  - Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, 
      Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and 
      Regeneration, Vienna, 1090, Austria.
FAU - Traxler, Denise
AU  - Traxler D
AD  - Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, 
      Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and 
      Regeneration, Vienna, 1090, Austria.
FAU - Beer, Lucian
AU  - Beer L
AD  - Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, 
      Austria.
FAU - Ristl, Robin
AU  - Ristl R
AD  - Section for Medical Statistics, Center for Medical Statistics, Informatics, and 
      Intelligent Systems, Medical University of Vienna, Vienna, 1090, Austria.
FAU - Golabi, Bahar
AU  - Golabi B
AD  - Department of Dermatology, Medical University of Vienna, Vienna, 1090, Austria.
FAU - Gabriel, Christian
AU  - Gabriel C
AD  - Red Cross Transfusion Service for Upper Austria, Linz, 4017, Austria.
FAU - Leutmezer, Fritz
AU  - Leutmezer F
AD  - Department of Neurology, Medical University of Vienna, Vienna, 1090, Austria.
FAU - Ankersmit, Hendrik Jan
AU  - Ankersmit HJ
AD  - Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, 
      Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and 
      Regeneration, Vienna, 1090, Austria.
LA  - eng
PT  - Journal Article
DEP - 20140619
PL  - England
TA  - F1000Res
JT  - F1000Research
JID - 101594320
PMC - PMC4215751
COIS- Competing interests: The Medical University of Vienna has claimed financial 
      interest (Patent number: PCT/EP09/67534, filed 18 Dec 2008; Patent name: 
      Pharmaceutical preparation comprising supernatant of blood mononuclear cell). 
      Hendrik Jan Ankersmit is a shareholder of APOSCIENCE AG, which owns the rights to 
      commercialize apoptotic MNC-secretomes for therapeutic use. All other authors 
      declare that they have no competing interests. APOSCIENCE AG is a funder of his 
      study.
EDAT- 2014/11/11 06:00
MHDA- 2014/11/11 06:01
PMCR- 2014/10/28
CRDT- 2014/11/13 06:00
PHST- 2014/10/20 00:00 [accepted]
PHST- 2014/11/13 06:00 [entrez]
PHST- 2014/11/11 06:00 [pubmed]
PHST- 2014/11/11 06:01 [medline]
PHST- 2014/10/28 00:00 [pmc-release]
AID - 10.12688/f1000research.4219.2 [doi]
PST - epublish
SO  - F1000Res. 2014 Jun 19;3:131. doi: 10.12688/f1000research.4219.2. eCollection 
      2014.