الفهرس 
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Abstract
The lung is one of the vital organs of the body and it is highly metabolic and synthetic organ composed of more than 40 cell type. The most prominent feature of its histology is the alveolar epithelium which is mostly formed of type I pneumocytes and few other types as type II pneumocytes and type III pneumocytes or brush cells. This alveolar epithelium is surrounded by the endothelium of the surrounding alveolar capillaries, but separated from it by interstitium. These three layers are considered as the air-blood barrier.
The air-blood barrier is permeable to oxygen and carbon dioxide that are present in the blood and in the air, thus it is concerned with gas exchange in the lungs. As a result of this fact, any disease affecting the air-blood barrier is considered as a fatal disease. The interstitial lung disease (ILD) is a group of diseases that affect the air-blood barrier causing its fibrosis and hence hinder the gas exchange between the blood and the air.
Bleomycin (BLM) is a therapeutic option for treatment of cancer specially germ-cell tumors, lymphomas and Kaposi’s squamous cell carcinoma. The therapeutic potency of BLM is believed to be related to its ability to cause both single- and double-stranded breaks in DNA in vitro.
Unfortunately after use of BLM for a long time as a safe chemotherapy for cancer, a dangerous side effect was appearing by the time. This side effect was diffuse interstitial pneumonitis that progresses to diffuse lung fibrosis.
The administration of BLM to rodents is considered to thoroughly reproduce the histologic alterations that are found in the human pulmonary fibrosis. The intratracheal administration of BLM in rats carries an advantage that a single injection produce rapid lung fibrosis in contrary to the other routes of administration. The first response in rat’s lung after intratracheal BLM injection appears after 3 days as inflammatory cellular infiltration followed by initiation of the fibrosis by day 7 which progresses to full development of fibrosis by day 15.
If the lung fibrosis as a fatal side effect of BLM is a bad news, the cellular therapy by stem cells as a promising new approach in treatment of varies diseases is considered as a good news.
Stem cells are present in different types including embryonic and adult stem cells. To gain the embryonic stem cells, the damage of the embryo at blastocyst stage is inevitable and so this is ethically prohibited. In contrary to that, the adult stem cells provide an alternative and ethically accepted source for the stem cells.
The first used source for adult stem cells was the bone marrow. Collection of bone marrow is very painful as it requires penetration of the bone in addition to that the frequency of incidence of graft-versus-host disease with stem cells isolated from the bone marrow is high.
Later on another source for adult stem cells was discovered which was the umbilical cord blood. It has the advantages of that it stem cells have more ability for differentiation and less incidence of graft-versus-host disease after their transplantation because the antigens of the blood cells are less developed.
In this research the ability of mononuclear cells (MNCs) that are isolated from the human umbilical cord blood and contains cord blood stem cells was assessed for prevention and treatment of the lung parenchymal fibrosis that was produced by intratracheal injection of BLM in adult rats.
The human umbilical cord blood was collected from gynecology department in Suez Canal University hospital and isolation of MNCs from it was carried out in the clinical pathology laboratory of Suez Canal University hospital.
The sample of the rats was divided into 6 groups according to the time of administration of BLM and cord blood MNCs . The lungs were collected from each rat and inflated by 10% neutral buffered formalin solution the fixed into 10% formalin the paraffin blocks were performed and lung sections were obtained and stained by Hematoxylin and Eosin, Masson trichrome and Heidenhain’s Azan trichrome stains.
The results of the research were collected and expressed into statistical analysis. The results revealed that the intratracheal injection of BLM in the rats produces inflammatory cellular infiltration within the first 5 days with the first development of the lung fibrosis also within the first 5 days. The full picture of pulmonary fibrosis appeared by day 28 after injection.
The administration of MNCs was performed in the rat’s tail vein after BLM administration at days 0, 5 and 10. the best results were obtained when the MNCs were transplanted at the same day of BLM injection (day 0). The effect of MNCs transplantation showed decrease by the delay after administration of BLM.
After obtaining of these results, we concluded that the MNCs that includes hematopoietic and mesenchymal stem cells that are isolated from human cord blood have the ability to repair the damage produced by the BLM injection. According to the above results the human umbilical cord blood MNCs can be used to treat cases of ILD and to protect from lung fibrosis in patients that use BLM as a chemotherapy for varies types of cancer.