Evidence that Bone Marrow Cells Do Not Contribute to the Alveolar Epithelium

Abstract

An ongoing controversy is the role of marrow cells in populating the alveolar epithelium. In this study, we employed flow cytometry and histologic techniques to evaluate this process. Donor bone marrow was harvested from transgenic mice expressing the LacZ or eGFP gene ubiquitously, or under the control of the human surfactant protein (SP)-C promoter, and transplanted into lethally irradiated, neonatal mice. In recipients transplanted with marrow that express eGFP or lacZ ubiquitously, light microscopy revealed cells whose morphology and location were compatible with a type II cell phenotype. Consistent with this, fluorescent microscopy suggested colocalization of eGFP and pro-SP-C proteins in single cells. In mice transplanted with SP-C-eGFP marrow, engraftment was not detectable by histology or flow cytometry. We therefore used deconvolution microscopy to reanalyze histologic sections that were thought to show marrow-derived type II cells. We found that all putative marrow-derived pneumocytes resulted from the overlapping fluorescent signals of an endogenous pro-SP-Cϩ type II cell and a donor-derived eGFPϩ cell. Taken together, our observations underscore the technical difficulties associated with evaluating engraftment in lung, and argue against a contributory role for marrow cells in populating the alveolar epithelium.

Differentiation of Mouse Induced Pluripotent Stem Cells Into Alveolar Epithelial Cells In Vitro for Use In Vivo

“…Although some studies have demonstrated the therapeutic potential of bone marrow-derived stem cells in rodent lung injury models [23,[26][27][28], there is no evidence of a role for these stem cells in populating the lung alveolar epithelium in vivo [29][30][31][32]. Recent studies have reported efficient and direct derivation of lung alveolar epithelium from murine embryonic stem cells (ESCs) [10,11,14,16] for in vitro and in vivo applications.…”

Minimally cultured bone marrow mesenchymal stem cells ameliorate fibrotic lung injury

“…bone marrow transplantation-induced lung reconstitution in transgenic mice infused with surfactant protein C-enhanced green fluorescent protein transgenic bone marrow cells [29,30].…”

Stem cells and cell therapies for cystic fibrosis and other lung diseases

“…As reviewed in that report, many of those studies were based on sex-mismatched transplantation and in situ demonstration of Y chromosome-containing donor marrow-derived cells in recipient lungs by fluorescence in situ hybridization (FISH), followed by immunohistochemical phenotyping of the donorderived cells [18]. However, as analytical techniques have improved, despite the earlier reports demonstrating substantial engraftment of lung epithelium with donor-derived cells, more recent reports demonstrate that only small numbers of transplanted adult marrowderived cells engraft in recipient lungs, particularly in airway or alveolar epithelium [19][20][21][22]. This includes only rare engraftment and CFTR expression in airway epithelium following transplantation of adult marrow-derived cells containing wildtype CFTR to CFTR KO mice [21] (Figure 2).…”