Rescue from Stx2-Producing E.?coli-Associated Encephalopathy by Intravenous Injection of Muse Cells in NOD-SCID Mice
| Autor: | Ryo Ozuru, Sohkichi Matsumoto, Shinsuke Kato, Kosuke Tashiro, Kaori Yasuda, Takahiro Tsuji, Muhammad Y. Amuran, Kimiharu Iwadate, Jun Fujii, Naoki Nishida, Yoichi Kurozawa, Noriko Konishi, Shohei Wakao, Junko Isobe, Morio Iino, Naoya Ohara, Takashi Matsuba, Eijiro Yamashita, Mari Dezawa, Arisato Yadoiwa, Misato Hida, Sari Matsumoto |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Cell Transplantation Mice SCID Shiga Toxin 2 Immunoglobulin G Disease Outbreaks Mice 0302 clinical medicine Japan Mice Inbred NOD Shiga toxin-producing Escherichia coli Drug Discovery Escherichia coli Infections Aged 80 and over 0303 health sciences Brain Diseases Mice Inbred ICR biology Shiga-Toxigenic Escherichia coli Brain Eculizumab Treatment Outcome 030220 oncology & carcinogenesis Injections Intravenous acute encephalopathy Molecular Medicine Female Original Article Stem cell medicine.drug Adult medicine.drug_class Encephalopathy Muse cells Monoclonal antibody Mesenchymal Stem Cell Transplantation Sudden death 03 medical and health sciences Genetics medicine Animals Humans Immunoadsorption Molecular Biology 030304 developmental biology Pharmacology Severe combined immunodeficiency business.industry medicine.disease Mice Inbred C57BL Disease Models Animal Immunology biology.protein business |
| Zdroj: | Ozuru, Ryo. Wakao, Shohei. Tsuji, Takahiro. et al. Rescue from Stx2-Producing E.coli-Associated Encephalopathy by Intravenous Injection of Muse Cells in NOD-SCID Mice. Molecular Therapy. 28. 100-118. 2020-01-08. Molecular Therapy |
| ISSN: | 1525-0016 |
| Popis: | Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis, hemolytic uremic syndrome, and acute encephalopathies that may lead to sudden death or severe neurologic sequelae. Current treatments, including immunoglobulin G (IgG) immunoadsorption, plasma exchange, steroid pulse therapy, and the monoclonal antibody eculizumab, have limited effects against the severe neurologic sequelae. Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative non-tumorigenic stem cells that naturally reside in the body and are currently under clinical trials for regenerative medicine. When administered intravenously, Musecells accumulate to the damaged tissue, where they exert anti-inflammatory, anti-apoptotic, anti-fibrotic, and immunomodulatory effects, and replace damaged cells by differentiating into tissue-constituent cells. Here, severely immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice orally inoculated with 9 × 109 colony-forming units of STEC O111 and treated 48 h later with intravenous injection of 5 × 104 Muse cells exhibited 100% survival and no severe after-effects of infection. Suppression of granulocyte-colony-stimulating factor (G-CSF) by RNAi abolished the beneficial effects of Muse cells, leading to a 40% death and significant body weight loss, suggesting the involvement of G-CSF in the beneficial effects of Muse cells in STEC-infected mice. Thus, intravenous administration of Muse cells could be a candidate therapeutic approach for preventing fatal encephalopathy after STEC infection. Graphical Abstract NOD-SCID mice orally inoculated with 9 × 109 colony-forming units of Shiga toxin-producing Escherichia coli (STEC) O111 and treated 48 h later with an intravenous injection of 5 × 104 human bone marrow-derived multilineage-differentiating stress-enduring (Muse) cells exhibited 100% survival. Thus, the intravenous administration of Muse cells might be a candidate therapeutic approach for preventing acute encephalopathy after STEC infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|