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Abstract
This discourse contains three perspectives on various aspects of Stem Cell Biology and tools available to study and translate into Regenerative Medicine. The lung incessantly faces onslaught of the environment, constantly undergoes oxidative stress, and is an important organ of detoxification. In degenerative diseases and inflammation, the lung undergoes irreversible remodeling that is difficult to therapeutically address and/or transplant a dying tissue. The other difficulty is to study its development and regenerative aspects to best address the aforementioned problems. This perspective therefore addresses- firstly, review of types of stem cells, their pathway of action and models in invertebrate organisms vis-a-vis microenvironment and its dynamics; secondly, stem cells in higher organisms and niche; and lastly data and inference on a novel approach to study stem cell destruction patterns in an injury model and information on putative lung stem cell niche. Stem cells are cryptic cells known to retain certain primitive characteristics making them akin to ancient cells of invertebrates, developmental stages in invertebrates and vertebrates and pliant cells of complex creatures like mammals that demonstrate stimulus-specific behavious, whether to clonally propagate or to remain well protected and hidden within specialized niches, or mobilize and differentiate into mature functionally operative cells to house-keep, repair injury or make new tissues. In lung fibrosis, alveolar epithelium degenerates progressively. In keeping with the goal of regenerative medicine, various models and assays to evaluate long and short term identity of stem cells and their niches is the subject of this perspective. We also report identification and characterization of functional lung stem cells to clarify how stem cell niches counteract this degenerative process. Inferences drawn from this injury model of lung degeneration using a short term assay by tracking side population cells and a long term assay tracking label retaining cells have been presented.
Highlights
Stem cells need to fulfill the following four criteria to be classed as stem cells; a. in order to maintain the stem cell population, stem cells should be capable of continuous self renewal b. stem cell should have the ability to differentiate into a variety of mature cells c. stem cells should be able to integrate and differentiate into its source damaged site d. lastly, stem
Bleomycin-induced Idiopathic Pulmonary Fibrosis model C57Bl/6 female mice (8–10 weeks of age) were intratracheally instilled with 0.075 U/ml bleomycin in 40 μl volume under brief isofluorane anesthesia and animals were maintained under SPF conditions in the UW animal facilities and sacrificed periodically to below-mentioned parameters (Figure 1)
Ancillary inflammatory parameters and inflammatory cell recruitment patterns were studied as follows: Assessment of extent of fibrotic and inflammatory damage in the lung post bleomycin treatment Mice were sacrificed at 10 weeks and blood, lung parenchyma enzymatically digested by dispase 1.2 U/ml and BALf were analysed
Summary
As defined by researchers stem cells are cells that have the ability of self renewal through cell division and differentiate into a diverse array of cell lines [1].In the general sense, stem cells need to fulfill the following four criteria to be classed as stem cells; a. in order to maintain the stem cell population, stem cells should be capable of continuous self renewal b. stem cell should have the ability to differentiate into a variety of mature cells c. stem cells should be able to integrate and differentiate into its source damaged site d. lastly, stemWith recent developments in the field and advancement of technologies like fluorescence activated cell sorting (FACS), magnetic activated cell sorting (MACS) along with enhanced isolation, culture and molecular imaging techniques [2] there has been much speculation of its use in therapy, regenerative medicine, drug and toxicity screening [1]. In order to maintain the stem cell population, stem cells should be capable of continuous self renewal b. For e.g. hematopoietic stem cells (HSCs) can restore tissue function by directly integrating into the target tissue while mesenchymal stem cells (MSCs) tend to deliver the signals to target tissues like in ischemic cardiac injury. There are a myriad of effectors of lung injury, including infectious agents, particulate and chemical pollutants, radiation, and host defense mechanisms gone awry. Many of these processes are ablative in nature and require repair mechanisms that regenerate mature lung tissue through cell proliferation and differentiation. Like the side population (SP) cells, have not yet been localized to a single lung compartment
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