title: The secretome of apoptotic human peripheral blood mononuclear cells attenuates secondary damage following spinal cord injury in rats.
abstract: After spinal cord injury (SCI), secondary damage caused by oxidative stress, inflammation, and ischemia leads to neurological deterioration. In recent years, therapeutic approaches to trauma have focused on modulating this secondary cascade. There is increasing evidence that the success of cell-based SCI therapy is due mainly to secreted factors rather than to cell implantation per se. This study investigated peripheral blood mononuclear cells as a source of factors for secretome- (MNC-secretome-) based therapy. Specifically, we investigated whether MNC-secretome had therapeutic effects in a rat SCI contusion model and its possible underlying mechanisms. Rats treated with MNC-secretome showed substantially improved functional recovery, attenuated cavity formation, and reduced acute axonal injury compared to control animals. Histological evaluation revealed higher vascular density in the spinal cords of treated animals. Immunohistochemistry showed that MNC-secretome treatment increased the recruitment of CD68(+) cells with concomitant reduction of oxidative stress as reflected by lower expression of inducible nitric oxide synthase. Notably, MNC-secretome showed angiogenic properties ex vivo in aortic rings and spinal cord tissue, and experiments showed that the angiogenic potential of MNC-secretome may be regulated by CXCL-1 upregulation in vivo. Moreover, systemic application of MNC-secretome activated the ERK1/2 pathway in the spinal cord. Taken together, these results indicate that factors in MNC-secretome can mitigate the pathophysiological processes of secondary damage after SCI and improve functional outcomes in rats.
authors: University Clinic for Trauma Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors: Thomas
authors: T
authors: Haider
authors: Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors: Romana
authors: R
authors: Höftberger
authors: Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
authors: Beate
authors: B
authors: Rüger
authors: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors: Michael
authors: M
authors: Mildner
authors: Center of Anatomy and Cell Biology, Medical University Vienna, Vienna, Austria.
authors: Roland
authors: R
authors: Blumer
authors: Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; Department of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors: Andreas
authors: A
authors: Mitterbauer
authors: Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; Department of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors: Tanja
authors: T
authors: Buchacher
authors: Department of Neurosurgery, Krankenanstalt Rudolfstiftung, Vienna, Austria.
authors: Camillo
authors: C
authors: Sherif
authors: Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; Department of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors: Patrick
authors: P
authors: Altmann
authors: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
authors: Heinz
authors: H
authors: Redl
authors: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria; Red Cross Blood Transfusion Service of Upper Austria, Linz, Austria.
authors: Christian
authors: C
authors: Gabriel
authors: Department of Cardiology, Medical University of Vienna, Vienna, Austria.
authors: Mariann
authors: M
authors: Gyöngyösi
authors: Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria; Center for Biomedical Technology, Danube University Krems, Krems, Austria.
authors: Michael B
authors: MB
authors: Fischer
authors: Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors: Gert
authors: G
authors: Lubec
authors: Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria; Department of Thoracic Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: hendrik.ankersmit@meduniwien.ac.at.
authors: Hendrik Jan
authors: HJ
authors: Ankersmit
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D064987:Cell- and Tissue-Based Therapy; D054360:Chemokine CXCL1 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000097:blood / Q000150:complications* / Q000628:therapy*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D054360:Chemokine CXCL1; D016207:Cytokines; D052247:Nitric Oxide Synthase Type II; D042461:Vascular Endothelial Growth Factor A; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Inflammation; MNC-secretome; Oxidative stress; PBMCs; Secondary damage; Spinal cord injury; Traumatic spinal cord injury