In vivo Models Serving ARDS research

Since our inception Melior has had a number of models representing pulmonary disease such as asthma.  With the COVID-19 pandemic we have expanded this capability with models especially suited for COVID-19 and ARDS.

The cytokine storm that is associated with COVID-19 subjects is closely linked to pulmonary complications including pulmonary extravasation (edema)^1-5.  Fluid laden pulmonary alveoli have poor oxygen exchange rates and are associated with reduced respiratory function. Patients experience lower oxygen saturation levels (SpO2) leading to Acute Respiratory Distress Syndrome (ARDS)  causing multiple organ failure and death.

Therefore, key components in this chain of events are pulmonary inflammation and pulmonary edema. For those patients who progress to ARDS but ultimately recover, some may still develop lasting pulmonary fibrosis.

Offering research scientists in their COVID-19 research studies, Melior routinely runs animal models that recapitulate aspects of a number of these key events including cytokine storm mediated pulmonary extravasation, reduced SpO2, and pulmonary fibrosis.

REFERENCES

1. Han J, et al. A critical role for Lyn kinase in strengthening endothelial integrity and barrier function. Blood. 2013 Dec 12;122(25):4140-9. doi: 10.1182/blood-2013-03-491423. Epub 2013 Oct 9. PMID: 24108461; PMCID: PMC3862279.

2. Kim MP, et al. Src family kinases as mediators of endothelial permeability: effects on inflammation and metastasis. Cell Tissue Res. 2009 Jan;335(1):249-59. doi: 10.1007/s00441-008-0682-9. Epub 2008 Sep 25. PMID: 18815812; PMCID: PMC3907084.

3. Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability. Physiol Rev. 2006 Jan;86(1):279-367. doi: 10.1152/physrev.00012.2005. PMID: 16371600.

4. Paul R, et al. Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke. Nat Med. 2001 Feb;7(2):222-7. doi: 10.1038/84675. PMID: 11175854.

5. Weis S, et al. Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction. J Clin Invest. 2004 Mar;113(6):885-94. doi: 10.1172/JCI20702. PMID: 15067321; PMCID: PMC362122.

Pulmonary Disease  Models

• • Allergic Asthma
  • Influenza
  • Pulmonary Edema
  • Pulmonary Fibrosis Model
  • Pulmonary Inflammation
  • Pulse Oximetry (SpO₂)