Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis

Stem Cells Transl Med. 2017 Oct;6(10):1905-1916. doi: 10.1002/sctm.16-0374. Epub 2017 Aug 7.

Abstract

Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis. Current animal and clinical studies focus on the use of adipose or bone marrow-derived mesenchymal stem cells. We, instead, have established adult lung spheroid cells (LSCs) as an intrinsic source of therapeutic lung stem cells. In the present study, we compared the efficacy and safety of syngeneic and allogeneic LSCs in immuno-competent rats with bleomycin-induced pulmonary inflammation in an effort to mitigate fibrosis development. We found that infusion of allogeneic LSCs reduces the progression of inflammation and fibrotic manifestation and preserves epithelial and endothelial health without eliciting significant immune rejection. Our study sheds light on potential future developments of LSCs as an allogeneic cell therapy for humans with pulmonary fibrosis. Stem Cells Translational Medicine 2017;9:1905-1916.

Keywords: Allogeneic; Fibrosis; Pulmonary; Stem cells; Syngeneic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / toxicity
  • Cells, Cultured
  • Female
  • Lung / cytology
  • Pulmonary Fibrosis / etiology
  • Pulmonary Fibrosis / therapy*
  • Rats
  • Rats, Wistar
  • Spheroids, Cellular / transplantation*
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / methods

Substances

  • Bleomycin