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CURATOR
A pinboard by
Oula Khoury

PhD student, Wake Forest Institute of Regenerative Medicine

PINBOARD SUMMARY

We are investigating the immunomodulatory properties of perinatal stem cells to treat lung disease

High levels of inflammation are associated with chronic inflammatory and immune mediated conditions such as CF. CF is associated with exaggerated and prolonged inflammation in the lungs, which contributes to lung injury, fibrosis and loss of lung function. When pulmonary infection is apparent in the CF airways, the adaptive and innate immune response is disproportionate and dysregulated. Even in the absence of clinically apparent infection there is often evidence of inflammation in the CF airways. CF patients show elevated levels of neutrophils in the lung, which have increased neutrophil elastase and myeloperoxidase activity. CF macrophages display spontaneous and exaggerated pulmonary infiltration, and are polarized into the M1 pro-inflammatory phenotype and to a lesser extent into the M2 anti-inflammatory phenotype. Cells of the adaptive immune system, such as T lymphocytes are more abundant in CF airways and produce high levels of inflammatory cytokines. Additionally an imbalance of T lymphocyte subsets may have an important role in the CF inflammatory response. Therapeutic regimens for CF generally involve management of symptoms in an attempt to slow the progression of the disease. However, it is the repeated cycles of inflammation, injury and fibrosis that cause the chronic, life-threatening manifestations that ultimately lead to respiratory failure. Thus, therapies that can target this inflammatory environment and disrupt the destructive cycle of infection, inflammation and fibrosis would have a major impact in preventing the progression of lung disease. Perinatal stem cells have anti-inflammatory properties that make them a promising cell therapeutic approach for treating CF.

Hypothesis: We hypothesize that perinatal stem cells are capable of modulating the chronic hyper-inflammatory environment of the CF lung. Results: Perinatal stem cells significantly reduced neutrophil and macrophage pulmonary migration into the lungs of the bleomycin injured mouse, and prevented pulmonary fibrosis and loss of lung function. In human samples, administration of perinatal stem cells decreased of pro-inflammatory cytokines such as IL-6.

Conclusions:
These preliminary data suggest that perinatal stem cell therapy may be a useful immune-modulatory therapy for CF.

4 ITEMS PINNED

Human mesenchymal stem cells reduce lung injury in immunocompromised mice but not in immunocompetent mice.

Abstract: The immunomodulatory and immunosuppressive capacity of human mesenchymal stem cells (hMSC) is well recognized, but efficacies of hMSC in immunocompetent and immunocompromised animals have never been directly compared.We aimed to compare the efficacy of hMSC in preventing bleomycin-induced lung injury in immunocompromised SCID and immunocompetent C57Bl/6 mice.SCID and C57Bl/6 mice were subjected to a single bolus intranasal instillation of bleomycin to induce lung injury. One million hMSC were administered intravenously 24 h following the induction of bleomycin lung injury.hMSC xenotransplantation into SCID mice resulted in transient improvements in lung weight and tidal volume and to persistent improvement in inspiratory duty cycle, inspiratory flow rate and inspiration/expiration ratio. We did not observed protective effects in C57Bl/6 mice. This correlated with histological changes, where hMSC administration reduced Ashcroft scores, collagen deposition and inflammatory influx in the lungs of SCID mice, but not in those of C57Bl/6 mice.The application of hMSC for the treatment of acute and chronic lung injury is significantly affected by the immune status of the recipient. Lack of hMSC-mediated repair observed in C57Bl/6 mice was likely to be due to limitations of their immune privilege and differential priming of hMSC in immunocompetent versus immunocompromised hosts.

Pub.: 05 Dec '12, Pinned: 18 Jul '17