Prominin-1/CD133⁺ Lung Epithelial Progenitors Protect from Bleomycin-induced Pulmonary Fibrosis

Abstract

The combined antiinflammatory and regenerative capacity of bone marrow-derived pulmonary epithelial progenitors offers a promising approach for development of cell-based therapeutic strategies against pulmonary fibrosis.

Therapeutic effect of lung mixed culture-derived epithelial cells on lung fibrosis

“…Similarly, LMDECs can be harvested at least two times from the same dish. After harvesting LMDECs from mixed culture at 9 DIV, the dishes were further incubated for 7-10 days (16)(17)(18)(19), and the round cells floating or loosely attached to the adherent cells appeared again. The yield of round cells was reduced by 10% compared with that at 9 DIV.…”

“…On the basis of the notion that dissection of pulmonary tissue might create a specific pathophysiological microenvironment leading to activation of tissue-resident progenitor cells, 16 we prepared a crude culture of enzymatically digested lung tissue, and observed the time-dependent changes in cell behavior of the mixed culture. As shown in Figure 1a, round cells arose from spindle-shaped adherent cells showing confluence at 5 DIV, and aggregates of spherelike cells were also observed.…”

“…We next investigated the cells using various markers as follows: CD34, a marker of hematopoietic stem/progenitor cells covering from earlier multipotent progenitors to later lineage-restricted progenitors, 28 and an enrichment marker tool for BASCs; 17 CD90, one of the major markers of tissueresident MSCs; 29 c-kit, a marker for human lung stem cells with ES-like pluripotency; 30 prominin-1 (CD133), a marker of progenitors (PEP) of alveolar epithelial cell lineage; 16 and LGR6, a marker of human alveolar multipotent cells. 31 Expression of CD34, CD90, c-kit, prominin-1, and LGR6 on LMDECs was rarely observed (Supplementary Figure 2).…”

“…[10][11][12] In addition to these stem cells, many groups have reported that certain populations of putative stem/progenitor cells are resident in the mouse lung. [13][14][15][16] Bronchioalveolar stem cells (BASCs) characterized by coexpression of Clara cell secretory protein (CCSP/CC10) and surfactant protein (SP)-C have differentiating capacity to both airway and alveolar lineages, and contribute to alveolar epithelial homeostasis and repair after injury. 14,17 On the other hand, a lineage-tracing investigation suggested that CCSP-expressing cells including BASCs do not contribute to either the alveolar epithelial cell population during normal homeostasis or alveolar epithelial regeneration after naphthalene injury.…”

Epithelial cell restoration and regeneration in inflammatory lung diseases

“…The role of alveolar epithelial type II cells in lung tissue repair has been the focus of recent investigation once again, and intratracheal administration of isolated epithelial type II cells was shown to improve bleomycin-induced lung fibrosis in rats 28) . Intratracheal administration of bone marrow-derived lung epithelial progenitors and amniotic epithelial cells was also revealed to attenuate bleomycin-induced lung fibrosis in mice [29][30] . Thus, cell therapy could be a promising approach even for IPF/UIP.…”