PMID- 25810725 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150326 LR - 20200930 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2015 DP - 2015 TI - Neuroprotective and antiapoptotic activity of lineage-negative bone marrow cells after intravitreal injection in a mouse model of acute retinal injury. PG - 620364 LID - 10.1155/2015/620364 [doi] LID - 620364 AB - We investigated effects of bone marrow-derived, lineage-negative cell (Lin(-)BMC) transplantation in acute retinal injury. Lin(-)BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin(-)BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin(-)BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin(-)BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin(-)BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors. FAU - Machalinska, Anna AU - Machalinska A AD - Department of Histology and Embryology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland ; Department of Ophthalmology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Roginska, Dorota AU - Roginska D AUID- ORCID: 0000-0001-8884-837X AD - Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Pius-Sadowska, Ewa AU - Pius-Sadowska E AD - Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Kawa, Milosz P AU - Kawa MP AD - Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Paczkowska, Edyta AU - Paczkowska E AD - Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Rudnicki, Michal AU - Rudnicki M AD - Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Lejkowska, Renata AU - Lejkowska R AD - Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Baumert, Bartlomiej AU - Baumert B AD - Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Wiszniewska, Barbara AU - Wiszniewska B AD - Department of Histology and Embryology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. FAU - Machalinski, Boguslaw AU - Machalinski B AD - Department of General Pathology, Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland. LA - eng PT - Journal Article DEP - 20150224 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC4354968 EDAT- 2015/03/27 06:00 MHDA- 2015/03/27 06:01 PMCR- 2015/02/24 CRDT- 2015/03/27 06:00 PHST- 2014/10/15 00:00 [received] PHST- 2015/01/02 00:00 [accepted] PHST- 2015/03/27 06:00 [entrez] PHST- 2015/03/27 06:00 [pubmed] PHST- 2015/03/27 06:01 [medline] PHST- 2015/02/24 00:00 [pmc-release] AID - 10.1155/2015/620364 [doi] PST - ppublish SO - Stem Cells Int. 2015;2015:620364. doi: 10.1155/2015/620364. Epub 2015 Feb 24.