Introduction
Stem cell therapy is a new therapeutic approach with a wide range of applications. Regenerative medicine repairs and replaces impaired cells or organs. Regenerative medicine includes tissue engineering, cell therapies, biomedical engineering techniques, and gene therapy procedures, which help in the formation of new functional tissues. Stem cells are present in every tissue of the human body and form an endogenous system of repair and regeneration. Several stem cell approaches have been formulated to help in lung regeneration.
What Are Stem Cells?
Stem cells are present in every tissue of the body and are partially differentiated or undifferentiated cells that are capable of differentiating into various cell types. These cells can proliferate indefinitely to produce numerous stem cells of the same variety. Stem cells are present in the embryonic stage and adults, with slightly different properties. Stem cells are different from progenitor cells, which cannot divide exponentially, and precursor cells, which can differentiate into only one cell type. Stem cells are specialized cells that are different from other cells in the human body. These cells can divide and renew for a long time and have the ability to become specialized cells, though they do not have specific functions. Therefore, the ability of stem cells to repair and regenerate could cure various lung diseases.
What Are the Types of Stem Cells?
Stem cells are categorized into intrinsic and extrinsic stem cells. Several stem cell types have been used in regenerative medicine, including embryonic stem cells, umbilical cord blood stem cells, adult cells, resident tissue stem cells, and bone marrow stem cells. A recent advancement is the discovery of induced pluripotent stem cells from adult cells. This is called reprogramming, in which a pluripotent state (capable of differentiating into several cell types) is established from a previously differentiated cell. The major stem cell type includes the following:
- Endogenous Tissue Stem Cells: Endogenous stem cells are undifferentiated cells that are present in almost all the tissues of the body. These cells participate in tissue maintenance and repair. Studies have shown that, in case of lung injury, stem cells originate from within the lung and participate in tissue regeneration. These stem cells are present in protected niches in the distal airway. These cells are called resident progenitor cells of alveolar, endothelial, and interstitial type. Endothelial progenitor cells originate from circulating bone marrow-derived vascular progenitor cells and function to repair and restore the structure and integrity of the injured tissues. These cells may differentiate into smooth muscle cells to participate in vascular remodeling. Following lung injury, endothelial progenitor cells localize to areas of injury and help decrease inflammation. Systemic administration of endogenous progenitor cells in adult and pediatric populations with primary pulmonary hypertension showed significant improvements in cardiopulmonary and symptomatic outcomes.
- Embryonic Stem Cells: Studies showed that intratracheal instillation of human embryonic stem cells, previously differentiated into alveolar epithelial cells, improved survival and reduced lung inflammation in lung injury. However, many of the genes expressed by embryonic cells are not expressed by endogenous stem cells in the lung.
What Are the Stem Cell-Based Approaches in Lung Diseases?
Studies have shown that multipotent stem cells can suppress the activation, proliferation, and effector functions of the immune cells. Multipotent stem cells are being used in cell therapy for immune and inflammatory disorders of the lung due to their potential benefits. Multipotent stem cell approaches in various lung disorders include the following:
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Stem Cells in Pulmonary Fibrosis:
Idiopathic pulmonary fibrosis is a condition that causes excessive deposition of the extracellular matrix within the interstitium, resulting in obliteration of the airway and the alveolar architecture. It is a progressive condition that remains unresponsive to pharmacological therapy and results in respiratory failure and death. Hence, studies were conducted to demonstrate the effects of multipotent stem cells (MSCs) in pulmonary fibrosis. Following the systemic administration of MSCs, only a small number of cells engrafted in the lung and caused a significant reduction in inflammation and collagen deposition. Pulmonary fibrosis is often diagnosed at later stages when there is significant fibrosis and inflammation that might be conducive to the potential effects of MSCs.
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Acute Lung Injury:
Acute lung injury is caused by local or systemic inflammation that disrupts the alveolar-capillary interface, causes leakage of protein-rich fluids, and inflammatory cell infiltration. As pharmacological interventions have not proven effective, studies were conducted on the administration of MSCs. MSCs increased survival and reduced lung damage and edema, protein leak, and hemorrhage (bleeding) in animal models of acute lung injury.
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Pulmonary Hypertension:
Though endogenous progenitor cells have been investigated for use in pulmonary hypertension, studies have demonstrated the efficacy of MSCs in pulmonary hypertension. Studies have shown that MSCs may offer protective effects and might completely reverse pulmonary hypertension and increase survival. Hence, MSCs may serve as an alternative or adjunct to the use of endogenous progenitor cells in the treatment of pulmonary hypertension.
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Bronchopulmonary Dysplasia:
Bronchopulmonary dysplasia and hypoplasia are characterized by a decrease in the number of alveolar epithelial and distal airway cells. These disorders impair the pulmonary function and the quality of life. Therefore, MSCs were used to demonstrate their effects on treating bronchopulmonary dysplasia. However, the mechanism of ameliorating hyperoxia-induced lung injury has not been established.
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Stem Cells in COPD:
Chronic obstructive pulmonary disease (COPD) constitutes emphysema and chronic bronchitis. COPD causes progressive alveolar destruction and respiratory dysfunction resulting in death. Symptomatic treatments help alleviate symptoms, but there is no cure for this disease except lung transplantation. MSC administration causes the release of growth factors that stimulate new alveolar growth. Hence, MSCs decrease chronic inflammation in COPD, thereby improving pulmonary function and quality of life.
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Bronchiolitis Obliterans:
Bronchiolitis obliterans is a chronic progressive disease that causes progressive obliteration of the airway. Administration of MSCs in bronchiolitis obliterans decreases inflammation, thereby preventing the obliteration of the airways.
Conclusion
Stem cells are a boon to lung regeneration. The ability of the stem cells to replace the defective cells and integrate into an injured site to restore the functional epithelium could favor the management of various lung disorders. Though recent advancements offer great promise, translational challenges regarding the development of strategies to regenerate an adult lung do exist. Therefore, various cellular subtypes identified potentially help in lung regeneration and repair. In addition, recent advancements have provided information on stem cell subtypes, their transition states, and the intricate pathway that helps in differentiation.
