Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats with focal ischemia.
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.
Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Vienna, 1090, Austria.
Patrick
P
Altmann
Department of Dermatology, Medical University of Vienna, Vienna, 1090, Austria.
Michael
M
Mildner
Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Vienna, 1090, Austria.
Thomas
T
Haider
Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Vienna, 1090, Austria.
Denise
D
Traxler
Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria.
Lucian
L
Beer
Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, 1090, Austria.
Robin
R
Ristl
Department of Dermatology, Medical University of Vienna, Vienna, 1090, Austria.
Bahar
B
Golabi
Red Cross Transfusion Service for Upper Austria, Linz, 4017, Austria.
Christian
C
Gabriel
Department of Neurology, Medical University of Vienna, Vienna, 1090, Austria.
Fritz
F
Leutmezer
Department of Thoracic Surgery, Medical University of Vienna, Vienna, 1090, Austria ; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Vienna, 1090, Austria.
Hendrik Jan
HJ
Ankersmit