Elisa Maria Amann1, Markus Thomas Rojewski1, Sinja Rodi2, Daniel Fürst2, Jörg Fiedler3, Annette Palmer4, Sonja Braumüller4, Markus Huber-Lang4, Hubert Schrezenmeier5, Rolf Erwin Brenner3. 1. Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, University of Ulm, Ulm, Germany; Institute of Transfusion Medicine, University of Ulm, Ulm, Germany. 2. Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, University of Ulm, Ulm, Germany. 3. Orthopedic Department, Division for Biochemistry of Joint and Connective Tissue Diseases, University of Ulm, Ulm, Germany. 4. Institute for Clinical and Experimental Trauma-Immunology, University of Ulm, Ulm, Germany. 5. Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, University of Ulm, Ulm, Germany; Institute of Transfusion Medicine, University of Ulm, Ulm, Germany. Electronic address: h.schrezenmeier@blutspende.de.
Abstract
BACKGROUND: Effective therapy of Acute Lung Injury (ALI) is still a major scientific and clinical problem. To define novel therapeutic strategies for sequelae of blunt chest trauma (TxT) like ALI/Acute Respiratory Distress Syndrome, we have investigated the immunomodulatory and regenerative effects of a single dose of ex vivo expanded human or rat mesenchymal stromal cells (hMSCs/rMSCs) with or without priming, immediately after the induction of TxT in Wistar rats. METHODS: We analyzed the histological score of lung injury, the cell count of the broncho alveolar lavage fluid (BAL), the change in local and systemic cytokine level and the recovery of the administered cells 24 h and 5 days post trauma. RESULTS: The treatment with hMSCs reduced the injury score 24 h after trauma by at least 50% compared with TxT rats without MSCs. In general, TxT rats treated with hMSCs exhibited a lower level of pro-inflammatory cytokines (interleukin [IL]-1B, IL-6) and chemokines (C-X-C motif chemokine ligand 1 [CXCL1], C-C motif chemokine ligand 2 [CCL2]), but a higher tumor necrosis factor alpha induced protein 6 (TNFAIP6) level in the BAL compared with TxT rats after 24 h. Five days after trauma, cytokine levels and the distribution of inflammatory cells were similar to sham rats. In contrast, the treatment with rMSCs did not reveal such therapeutic effects on the injury score and cytokine levels, except for TNFAIP6 level. CONCLUSION: TxT represents a suitable model to study effects of MSCs as an acute treatment strategy after trauma. However, the source of MSCs has to be carefully considered in the design of future studies.
BACKGROUND: Effective therapy of Acute Lung Injury (ALI) is still a major scientific and clinical problem. To define novel therapeutic strategies for sequelae of blunt chest trauma (TxT) like ALI/Acute Respiratory Distress Syndrome, we have investigated the immunomodulatory and regenerative effects of a single dose of ex vivo expanded human or rat mesenchymal stromal cells (hMSCs/rMSCs) with or without priming, immediately after the induction of TxT in Wistar rats. METHODS: We analyzed the histological score of lung injury, the cell count of the broncho alveolar lavage fluid (BAL), the change in local and systemic cytokine level and the recovery of the administered cells 24 h and 5 days post trauma. RESULTS: The treatment with hMSCs reduced the injury score 24 h after trauma by at least 50% compared with TxT rats without MSCs. In general, TxT rats treated with hMSCs exhibited a lower level of pro-inflammatory cytokines (interleukin [IL]-1B, IL-6) and chemokines (C-X-C motif chemokine ligand 1 [CXCL1], C-C motif chemokine ligand 2 [CCL2]), but a higher tumor necrosis factor alpha induced protein 6 (TNFAIP6) level in the BAL compared with TxT rats after 24 h. Five days after trauma, cytokine levels and the distribution of inflammatory cells were similar to sham rats. In contrast, the treatment with rMSCs did not reveal such therapeutic effects on the injury score and cytokine levels, except for TNFAIP6 level. CONCLUSION: TxT represents a suitable model to study effects of MSCs as an acute treatment strategy after trauma. However, the source of MSCs has to be carefully considered in the design of future studies.
Authors: Elisa Maria Amann; Alexander Groß; Markus Thomas Rojewski; Hans Armin Kestler; Miriam Kalbitz; Rolf Erwin Brenner; Markus Huber-Lang; Hubert Schrezenmeier Journal: PLoS One Date: 2019-05-14 Impact factor: 3.240
Authors: Lacy E Lowry; Maryanne C Herzig; Barbara A Christy; Richard Schäfer; Shibani Pati; Andrew P Cap; James A Bynum Journal: Stem Cell Rev Rep Date: 2021-01-08 Impact factor: 6.692