Bone Marrow Stromal Cell Therapy Reduces proNGF and p75 Expression in Mice with Experimental Autoimmune Encephalomyelitis
| Autor: | Jing Zhang, Michael Chopp, Stanton B. Elias, Mei Lu, Qi Gao, Jade Borneman, Xuguang Zheng, Cynthia Roberts, Smita Savant-Bhonsale, Chaya Brodie, Yi Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
musculoskeletal diseases
Pathology medicine.medical_specialty Stromal cell Encephalomyelitis Autoimmune Experimental Encephalomyelitis Apoptosis Bone Marrow Cells Receptors Nerve Growth Factor Biology Motor Activity Nerve Fibers Myelinated Article Cell Line Mice Nerve Growth Factor medicine Animals Protein Precursors Cells Cultured Bone Marrow Transplantation Neurons Experimental autoimmune encephalomyelitis Brain hemic and immune systems Recovery of Function medicine.disease Oligodendrocyte biological factors Mice Inbred C57BL Oligodendroglia medicine.anatomical_structure Nerve growth factor Neurology nervous system Cancer research Neuroglia Female Neurology (clinical) Bone marrow sense organs Stromal Cells |
| Popis: | Demyelination is prominent in experimental autoimmune encephalomyelitis (EAE). The receptor p75 and its high affinity ligand proNGF are required for oligodendrocyte death after injury. We hypothesize that bone marrow stromal cells (BMSCs) provide therapeutic benefit in EAE mice by reducing proNGF/p75 expression. PBS or BMSCs (2 x 10(circumflex)6) were administered intravenously on the day of EAE onset. Neurological function and demyelination areas were measured. Immunohistochemical staining was used to measure apoptotic oligodendrocytes, expression of proNGF and p75, and the relationship between proNGF and p75 in neural cells. proNGF was used to treat oligodendrocytes in culture with or without BMSCs. EAE mice exhibited neurological function deficit and demyelination, and expression of proNGF and p75 was increased. BMSC treatment improved functional recovery, reduced demyelination area and apoptotic oligodendrocytes, decreased expression of proNGF and p75 compared with PBS treatment. proNGF(+) cells colocalized with neural cell markers, while p75 colocalized with an oligodendrocytic marker, and proNGF colocalized with p75. proNGF induced apoptosis of oligodendrocytes in vitro, and p75 antibody blocked this apoptotic activity. BMSCs reduced p75 expression and apoptotic activity in oligodendrocytes with proNGF treatment. BMSC treatment benefits on EAE mice may be fostered by decreasing the cellular expression of proNGF and p75, thereby reducing oligodendrocyte death. |
| Databáze: | OpenAIRE |
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