Cells Derived from the Circulation Contribute to the Repair of Lung Injury

Abstract

Bone marrow (stem/progenitor) cells have been shown to "differentiate" into cells in multiple tissues, including lung. A low number of hematopoietic stem/progenitor cells also circulate in peripheral blood. The physiologic roles of these cells are still uncertain. This study was designed to test, using parabiotic mice that were joined surgically, whether stem/progenitor cells in blood contributed to the regeneration of lung after injury. Parabiotic mice were generated surgically by joining green fluorescent protein transgenic mice and wild-type littermates. These mice developed a common circulation (approximately 50% green cells in blood) by 2 weeks after surgery. The wild-type mouse was either uninjured or lethally irradiated or received intratracheal elastase or the combination of radiation with intratracheal elastase injection. Radiation or the combination of radiation with elastase significantly increased the proportion of bright green cells in the lungs of the wild-type mice. Morphologically, interstitial monocytes/macrophages, subepithelial fibroblast-like interstitial cells, and additionally type I alveolar epithelial cells immunostained for green fluorescent protein in wild-type mice. Approximately 5 to 20% of lung fibroblasts primary cultured from injured wild-type mice were green fluorescent protein expressing cells, indicating their blood derivation. This study demonstrates that stem/progenitor cells in blood contribute to the repair of lung injury in irradiated mice.

Impaired Colony-Forming Capacity of Circulating Endothelial Progenitor Cells in Patients with Emphysema

“…Supporting this are several recent studies suggesting that bone marrow-derived stem cells may play an important role in the regeneration of injured lungs (Krause et al 2001;Theise et al 2002;Epperly et al 2003;Ortiz et al 2003;Abe et al 2004;Ishizawa et al 2004;Aliotta et al 2005). For example, after whole bone marrow or CD34 + Lin − cells are transplanted into lethally-irradiated female mice, they differentiate into bronchiolar epithelia and type 2 pneumocytes (Theise et al 2002).…”

“…A number of reports propose that bone marrow-derived stem cells contribute to the repair of injured organs, including the lung (Krause et al 2001;Theise et al 2002;Epperly et al 2003;Ortiz et al 2003;Abe et al 2004;Ishizawa et al 2004;Yamada et al 2004;Aliotta et al 2005). Endothelial progenitor cells (EPCs) that mobilize from the bone marrow are thought to play key roles in the maintenance of vascular integrity, and to act as "repair cells" in response to endothelial injury .…”

Mechanisms Promoting Chronic Lung Diseases: Will Targeting Stromal Cells Cure COPD and IPF?

“…Human and mouse studies have demonstrated that fibrocytes from peripheral blood migrate to skin wound chambers [49][50][51] and bronchial mucosa after antigen challenge 52 . Furthermore, these cells have been reported in disease states with fibrotic pathologies including hypertrophic scars, asthma and IPF [52][53][54][55] . Fibrocytes are pleiotropic and may contribute to fibrogenesis by directly producing collagen, as well as inflammatory cytokines, hematopoietic growth factors, and chemokines [54][55][56][57][58] (Fig.…”

Método imunomagnético associado ao meio MesenCult® na obtenção de células mononucleares da medula óssea de coelhos negativas para o anticorpo monoclonal CD45

“…Para expansão, é necessário isolá-las e purificá-las, sendo que ao se multiplicarem em cultura, caracterizam--se por apresentarem aderência ao plástico, ter aspecto de fibroblastos e se diferenciar em células distintas (Yu et al 2004). Após o isolamento e expansão podem se diferenciar em osteoblastos (Kassel, Roskilde & Erikson 1993), múscu-lo esquelético (Sampaolesi et al 2005), endotélio (Abe et al 2004), cardiomiócitos (Lima, Soares & Santos 2009), hepatócitos (Justesen et al 2002), adipócitos (Jiang et al 2002), tecido tendíneo (Kwan, Wan & Longaker 2003) e neurônios (Mendez-Otero et al 2009). …”