Following damage, the majority of bone marrow-derived airway cells express an epithelial marker

MacPherson, Heather; Keir, Pamela A; Edwards, Carol J; Webb, Shaun; Dorin, Julia R.

doi:10.1186/1465-9921-7-145

Cited by 28 publications

(29 citation statements)

References 33 publications

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“…Although in concordance with some recent reports (46,48,58,59), the lack of epithelial differentiation in this study is in sharp contrast with earlier reports describing up to 20% donorderived epithelial cells after marrow or stem cell transplantation (38)(39)(40)(41)(42)(43). As has been suggested by others (48), we speculate that these discrepant results may be attributed, at least in part, to variations in interpretation of the fluorescence findings.…”

Section: Discussioncontrasting

confidence: 57%

Fate and Effects of Adult Bone Marrow Cells in Lungs of Normoxic and Hyperoxic Newborn Mice

Fritzell

Mao²,

Gundavarapu³

et al. 2009

Am J Respir Cell Mol Biol

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Cell-based therapy in adult lung injury models is associated with highly variable donor cell engraftment and epithelial reconstitution. The role of marrow-derived cell therapy in neonatal lung injury is largely unknown. In this study, we determined the fate and effects of adult bone marrow cells in a model of neonatal lung injury. Wild-type mice placed in a normoxic or hyperoxic (95% O 2 ) environment received bone marrow cells from animals expressing green fluorescent protein (GFP) at Postnatal Day (P)5. Controls received vehicle buffer. Lungs were analyzed between Post-Transplantation (TPX) Day 2 and Week 8. The volume of GFP-immunoreactive donor cells, monitored by stereologic volumetry, remained constant between Post-TPX Weeks 1 and 8 and was similar in normoxic and hyperoxiaexposed recipients. Virtually all marrow-derived cells showed colocalization of GFP and the pan-macrophage marker, F4/80, by double immunofluorescence studies. Epithelial transdifferentiation was not seen. Marrow cell administration had adverse effects on somatic growth and alveolarization in normoxic mice, while no effects were discerned in hyperoxia-exposed recipients. Reexposure of marrowtreated animals to hyperoxia at P66 resulted in significant expansion of the donor-derived macrophage population. In conclusion, intranasal administration of unfractionated bone marrow cells to newborn mice does not achieve epithelial reconstitution, but establishes persistent alveolar macrophage chimerism. The predominantly adverse effects of marrow treatment in newborn lungs are likely due to macrophage-associated paracrine effects. While this model and route of cell therapy may not achieve epithelial reconstitution, the role of selected stem cell populations and/or alternate routes of administration for cell-based therapy in injured newborn lungs deserve further investigation.Keywords: stem cells; cell therapy; lung injury; newborns; BPD Premature infants with structurally immature lungs born between 23 and 28 weeks of gestation are at risk for development of bronchopulmonary dysplasia (BPD) or chronic lung disease of the newborn, a condition associated with high perinatal morbidity and mortality (1). An estimated 30% of infants with a birth weight between 500 and 1,500 g will develop BPD. Many of these infants require long-term ventilation and/or supplemental oxygen (2, 3). The main pathological hallmark of BPD is an arrest of alveolar development, characterized by large and simplified distal airspaces (4, 5). In addition, several recent reports have shown that the lungs of ventilated preterm infants with early BPD show markedly increased levels of alveolar epithelial cell death (6-8).We recently demonstrated that increased alveolar epithelial apoptosis in newborn mice is sufficient to disrupt alveolar remodeling (9), supporting our central hypothesis that loss of alveolar epithelial cells may play a critical role in the arrested alveolar development seen in BPD. The potential for stem cell-based therapy aimed at restoring or protecting the alveol...

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Section: Discussioncontrasting

confidence: 57%

Fate and Effects of Adult Bone Marrow Cells in Lungs of Normoxic and Hyperoxic Newborn Mice

Fritzell

Mao²,

Gundavarapu³

et al. 2009

Am J Respir Cell Mol Biol

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“…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).…”

Section: Lung Repair and Remodeling With Adult Bone Marrow-derived Stmentioning

confidence: 94%

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

Weiss

2008

Pulmonary Pharmacology & Therapeutics

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This review will critically evaluate recent findings suggesting that embryonic stem cells and stem cells derived from adult tissues, including bone marrow and umbilical cord blood, may be utilized in repair and regeneration of injured or diseased lungs. This is an exciting and rapidly moving field that holds promise as a novel therapeutic approach for cystic fibrosis and other lung diseases. However, while early studies suggested substantial lung remodeling, particularly with bone marrow-derived cells, more recent findings suggest that engraftment of adult marrow-derived cells in lung is a rare event of uncertain significance. Most recently, it has been suggested that a more relevant role of adult marrow-derived stem cells in lung is modulation of local inflammatory and immune responses. This review will also describe recent advances in understanding of local stem and progenitor cells in lung and their roles in lung development and repair.

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“…Examples of the second group, the exogenous stem cells, are: (2a) embryonic stem (ES) cells derived from the inner cell mass of a blastocyst-stage embryo (Coraux et al, 2005), or (human) amniotic fluid stem cells (Carraro et al, 2008), (2b) side-population (SP) cells from bone marrow, isolated by virtue of their ability to exclude the DNA-binding dye Hoechst 33342 (MacPherson et al, 2005;MacPherson et al, 2006), and epithelial stem cells present in bone marrow or in the circulation (Gomperts et al, 2006;Gomperts et al, 2007), (2c) fat-derived mesenchymal cells , and (2d) induced pluripotent stem (iPS) cells (Takahashi and Yamanaku, 2006;Geoghegan and Byrnes, 2008).…”

Section: Exogenous Stem Cellsmentioning

confidence: 99%

“…A possible role of exogenous SP cells in lung repair was demonstrated by studies of MacPherson et al (2005MacPherson et al ( , 2006. SP cells were isolated from the bone marrow of male mice, and seeded on tracheae from female mice, after the epithelium had been removed by treatment with 2% polidocanol.…”

Section: Exogenous Stem Cellsmentioning

confidence: 99%

“…One week after removal of the original epithelium, the epithelium had regrown, and it could be shown that a small proportion of cells had a Y chromosome and hence was of donor origin ("sex mismatch chimera") (MacPherson et al, 2005). The donor cells had epithelial characteristics as shown by cytokeratin expression, but also hematopoietic characteristics as shown by CD45 expression (MacPherson et al, 2006). Gomperts et al (2006) found another population of progenitor epithelial cells in bone marrow and in the circulation in mice.…”

Section: Exogenous Stem Cellsmentioning

confidence: 99%

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Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

Roomans

2010

eCM

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Stem/progenitor cells can be used to repair defects in the airway wall, resulting from e.g., tumors, trauma, tissue reactions following long-time intubations, or diseases that are associated with epithelial damage. Several potential sources of cells for airway epithelium have been identified. These can be divided into two groups. The first group consists of endogenous progenitor cells present in the respiratory tract. This group can be subdivided according to location into (a) a ductal cell type in the submucosal glands of the proximal trachea, (b) basal cells in the intercartilaginous zones of the lower trachea and bronchi, (c) variant Clara cells (Clara v -cells) in the bronchioles and (d) at the junctions between the bronchioles and the alveolar ducts, and (e) alveolar type II cells. This classification of progenitor cell niches is, however, controversial. The second group consists of exogenous stem cells derived from other tissues in the body. This second group can be subdivided into: (a) embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, or amniotic fluid stem cells, (b) side-population cells from bone marrow or epithelial stem cells present in bone marrow or circulation and (c) fat-derived mesenchymal cells. Airway epithelial cells can be co-cultured in a system that includes a basal lamina equivalent, extracellular factors from mesenchymal fibroblasts, and in an air-liquid interface system. Recently, spheroid-based culture systems have been developed. Several clinical applications have been suggested: cystic fibrosis, acute respiratory distress syndrome, chronic obstructive lung disease, pulmonary fibrosis, pulmonary edema, and pulmonary hypertension. Clinical applications so far are few, but include subglottic stenosis, tracheomalacia, bronchiomalacia, and emphysema.

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Following damage, the majority of bone marrow-derived airway cells express an epithelial marker

Cited by 28 publications

References 33 publications

Fate and Effects of Adult Bone Marrow Cells in Lungs of Normoxic and Hyperoxic Newborn Mice

Fate and Effects of Adult Bone Marrow Cells in Lungs of Normoxic and Hyperoxic Newborn Mice

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

Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

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