The lung is in direct contact with the environment which is highly contaminated with microbes and pollutants, the result of which is damage to structural cells. Under these conditions the affected cells must be repaired. Compensation of dying structural cells of lung is done by endogenous progenitor cells. Endogenous stem cells have ability for regeneration damaged epithelium via conformity their function and structure. The capability of the lung precursor cells for repair and development declins with aging, and these cells are not usually enough for relief extensive damages. The objective of exogenous stem cells transplantation (such as embryonic, adults, etc.) and the differentiated lung cells are replacement of the damaged cells. The exogenous stem cells transplantation in animal models has demonstrated, which the cells can be replaced in the lung and developed into the adult phenotypes. Exogenous stem cells-based treatments, have produced a new method for the lung diseases. The stem cell therapy and the use of differentiated lung cells are effective in the repair of damaged lung because the cells can replace the damaged cells and support endogenous renovation and development. Introduction: The lung is a complex structure with alveoli millions, many airways and wide vascular surface that carry out the gas exchange. The lung is in direct contact with the environment and during normal breathing, the airways transmit large volumes of air, which is highly contaminated with microbes and pollutants but lung has multi-faceted defense mechanisms, which are important for survival (Hogg et al., 2004; MokhberDezfouli et al., 2017). Despite these defensive barriers, respiratory system is vulnerable, the result of which is damage to structural cells. Under these conditions the affected cells must be renewed or die by apoptosis or necrosis. Compensation of dying structural cells of lung is done by endogenous progenitor cells to be improved (Moodley et al., 2011). Repair and regeneration of damaged pulmonary cells are slower compared to other cells in the adult tissues for example intestinal and skin cells. However, the possibility of repairing and regeneration the damaged pulmonary cells occurs after respiratory infection (Barkauskas et al., 2013). So understanding lung regeneration capacity and role of stem cells are extremely important for use of therapeutic. The diseases of lung respond differently to the present therapies and their continuation will lead to death. Although diagnosis of timely and rapid and pharmaceutical treatments lead to improvement of early symptoms but the abilities and daily activities of patients are decreased and the disease signs may again reveal in the long term. Also, in some patients, the only option for survival is the lung transplantation while there is the severe shortage in the lung donor (Sueblinvong and Weiss, 2010). Therefore, further researches should be done on ways, which can increase the lung repair and regeneration and help in the pulmonary diseases treatment. The recent results represent, which the stem cells application can be effective in regeneration and repair of the damaged tissue (Wang et al., 2010). Therefore, one way for treatment of lung diseases is stem cell therapy, which can replace the cells of damaged and endothelial epithelial and support endogenous cells renovation. When the progenitor cells activity of lung is impaired due to damage, replacement of endothelial and epithelial cells is disrupted. This leads to renovation disruption (MokhberDezfouli et al., 2017). The stem cells application can help in replacement of endothelial and epithelial cells after severe damages. Furthermore, the healthy part of the lung can enhance the healing process and prevent fibrosis via the regeneration stimulation and possible mechanisms including immunomodulation and the release of trophic factors (Moodley et al., 2011). Development of lung: First, the definitive endoderm forms from inner cell mass after gastrulation. Then, the definitive endoderm develops the gut tube and is patterned along the anterior-posterior and the dorsal-ventral axes via the paracrine signals from the mesoderm (Zorn and Wells, 2009). Nkx2.1+ endoderm buds from the ventral anterior foregut to form the lung sprouts and then causes uniform divergence to develop the respiratory tree. Differentiation of cell continues in the early postnatal period to generate the multiple cell types, which the adult lung develop (Morrisey and Hogan, 2010; SadeghianChaleshtori et al., 2016). For production of pulmonary epithelial cells in vitro should pursue the same development as the fetal lung in the culture medium. So that, the stem cells should be induced to spread the definitive endoderm, followed by the generation of anterior foregut endoderm, and ultimately differentiation into the the lung lineages. The researchers have showed remarkable advance in the development of differentiated lung cells from the stem cells (Roszell et al., 2009; Schmeckebier et al., 2013; Huang et al., 2014; MokhberDezfouli et al., 2019). In the future, more knowledge of normal development of lung may help researchers for prevent from the pulmonary abnormalities. The lung repair process in damage: The pulmonary repair process after damage is a complex phenomenon. Endogenous stem cells have ability for regeneration damaged epithelium via conformity their function and structure. The examination on airways epithelium repair display that the improvement process of airway epithelium inclusive differentiation, migration of adjacent cells for cover the empty region, the progenitor cells proliferation for repair cell number and the cells differentiation for regeneration the cells function (Kamaruzaman et al., 2013; SadeghianChaleshtori et al., 2020a). The airways epithelium after injury, starts the improvement process for repair the blood-air barrier integrity. The cells of ATII differentiate into the cells of ATI that repair the epithelial coverage entirety. Polymorphonuclear leukocytes act until restore the pulmonary damage with secretion of the destructive agents. Meantime, the macrophages and alveolar cells eliminate the compounds of protein from the alveoli and the lung function improve (Saguil A, Fargo, 2012; SadeghianChaleshtori et al., 2020a). Stem cells and precursor cells: The stem cells can repair the damaged cells location by the internal renewal system (Biehl and Russell, 2009). The potential sources of precursor cells are recognized for the airways and lung epithelium and are distributed into two groups: the stem cells of endogenous and exogenous. The lung is a complex organ with more than forty types of different cell that there are distinct populations of progenitor cells in separate anatomical zones along the respiratory tree (Sueblinvong and Weiss, 2010). Moreover, the essential role of precursor cells of lung in repairing and regeneration the damage, the epithelial cells reversible phenotype and mucus plays an significant role in the damage repair (Wang et al., 2007). There are the endogenous stem cells types in the airways and lung. The capability of the lung precursor cells for restore (that is often discussed as the natural regeneration capacity) declins with aging, and these cells are not usually enough for relief extensive damages (SadeghianChaleshtori et al., 2020a). The objective of exogenous stem cells transplantation (such as embryonic, adults, etc.) and the differentiated lung cells are replacement of the dead cells or the damaged cells. The autologous or allogenic stem cells transplantation in animal models has demonstrated, which the cells can be replaced in the lung and developed into the adult phenotypes and as a result, the cellular response enhancement to injury (Kotton et al., 2001; SadeghianChaleshtori et al., 2020a). Exogenous stem cells-based treatments, have produced a new method for the lung diseases such as acute respiratory distress syndrome (Sadeghian Chaleshtori et al., 2020b). Conclusion: In the future, more knowledge of normal development of lung may help researchers for prevent from the pulmonary abnormalities. The capability of the lung precursor cells for repair and development declins with aging, and these cells are not usually enough for relief extensive damages. The exogenous stem cells transplantation in animal models has demonstrated, which the cells can be replaced in the lung and developed into the adult phenotypes. The stem cell therapy is effective in the repair damaged lung because the cells can replace the damaged cells.
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