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Battling Lung Fibrosis with Allogeneic Lung Spheroid Cells

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Review of “Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Current therapeutic strategies for idiopathic pulmonary fibrosis (IPF), a chronic, progressive, life-threatening disease characterized by dysfunction of the lung interstitium and poor oxygen acquisition, treat the symptoms and not the disease and their application entails numerous unwanted side effects [1].

In the search for alternative treatments for disorders such as IPF, many researchers turn to mesenchymal stem cells (MSCs) derived from bone marrow or adipose tissue. However, researchers from the laboratories of Ke Cheng (North Carolina State University, Raleigh, NC, USA) and Leonard Jason Lobo (University of North Carolina, Chapel Hill, NC, USA) instead turned to adult lung spheroid cells (LSCs) [2] as a source of therapeutic lung stem cells. 

Their new STEM CELLS Translational Medicine study, which employs a rat model of interstitial lung disease [3], assessed the abilities of syngeneic and allogeneic LSCs to attenuate pulmonary fibrosis [4], with the hope of translating this approach to human patients.

To generate LSCs, Cores et al. first plated patient-derived lung spheroids onto fibronectin-coated flasks, where they dissociated and proliferated to yield sufficient cell numbers for assessment and transplantation. In vitro analysis suggested that LSC-secreted factors reduced fibrosis and promoted angiogenesis via paracrine mechanisms, while in vivo, intravenous delivery of both syngeneic and allogeneic LSCs inhibited the onset of fibrosis in rats following bleomycin-induced pulmonary inflammation. Both LSC types protected alveolar cells (pneumocytes - Aquaporin‐5‐positive green cells in the adjoined figure), inhibited pulmonary apoptosis, and promoted angiogenesis, while allogeneic LSC transplantation did not elicit systemic or local immune rejection.

The authors hope that the therapeutic success of allogeneic LSCs in their rat model may alter the future of cell-based treatment of lung disease. The availability of lung tissue from various sources (surgical and transplant discards, and recently deceased cadavers) will allow for the expansion and storage of a vast number of allogeneic LSCs with the potential to quickly and cost-effectively treat scores of patients.

The team behind this new study now aspire to study allogeneic LSC treatment in larger animal models with the expectation of translating their therapeutic strategy from the bench to the bedside. Stay tuned to the Stem Cells Portal to see how this exciting new approach progresses!

References

  1. Ratner, M., Landmark approvals in idiopathic pulmonary fibrosis. Nat Biotechnol 2014;32:1069-70.
  2. Dinh, P.C., et al., Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies. Respir Res 2017;18:132.
  3. Henry, E., et al., Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis. Stem Cells Transl Med 2015.
  4. Cores, J., et al., Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis. STEM CELLS Translational Medicine 2017;6:1905-1916.