Int J Stem Cells.  2014 May;7(1):1-11.

Comparative Study between Intravenous and Intraperitoneal Stem Cell Therapy in Amiodarone Induced Lung Injury in Rat

• Zickri MB
• Fadl SG
• Metwally H

Abstract

BACKGROUND AND OBJECTIVES
The fibrosing form of lung injury (occupational, environmental, infective or drug induced) is associated with significant morbidity and mortality. Amiodarone (AM), often prescribed for control of arrhythmias is considered a potential cause. No effective treatment was confirmed, except lung transplantation. Intravenous (IV) stem cell therapy may produce pulmonary emboli or infarctions. Despite being commonly used in clinical practice, the intraperitoneal (IP.) route has been rarely used for cell delivery. The present study aimed at investigating and comparing the possible effect of IP stem cell therapy (SCT) on pulmonary toxicity versus the intravenous route in a rat model of amiodarone induced lung damage.
METHODS AND RESULTS
36 adult male albino rats were divided into 4 groups. Rats of AM group were given 30 mg/kg daily orally for 4 weeks. Rats of IV SCT group were injected with stem cells in the tail vein. Rats of IP SCT group received IP cell therapy. Histological, histochemical, immunohistochemical and morphometric studies were performed. Obstructed bronchioles, overdistended alveoli, reduced type I pneumocytes, increased thickness of alveolar septa and vessels wall besides increased area% of collagen fibers regressed in response to IV and IP SCT. The improvement was more obvious in IV group. The area% of Prussion blue +ve and CD105 +ve cells was significantly higher in IV group.
CONCLUSIONS
Cord blood MSC therapy proved definite amelioration of lung injury ending in fibrosis. The effect of IP SCT was slightly inferior to that of IV SCT, which may be overwhelmed by repeated IP injection.

Keyword

Mesenchymal stem cells; Amiodarone; Cord blood; Lung injury

MeSH Terms

Adult
Amiodarone*
Animals
Arrhythmias, Cardiac
Bronchioles
Cell- and Tissue-Based Therapy
Collagen
Fetal Blood
Fibrosis
Humans
Infarction
Lung
Lung Injury*
Lung Transplantation
Male
Mesenchymal Stromal Cells
Models, Animal
Mortality
Pneumocytes
Rats*
Stem Cells*
Veins
Amiodarone
Collagen

Figure

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  Fig. 1. (A) Section in the lung of a control rat showing two bronchioles (b), alveoli (a), alveolar sacs (S) and a vessel (v) (H&E, ×100). (B) Section in the lung of a control rat showing alveoli (a) and alveolar sacs (S) lined by multiple cells exhibiting flat nuclei (arrows). Note alveolar septa (I) (H&E, ×400).

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  Fig. 2. (A) Section in the lung of a rat in amiodarone group showing a small bronchiole with partial obliteration of the lumen by shed epithelial cells (*), thickened wall of two vessels (v), cellular aggregates in alveolar septa and cellular infiltration in the adventitia of bronhiole (arrowheads) (H&E, ×100). (B) Section in the lung of a rat in amiodarone group showing thickening of the alveolar septa exhibiting dense cellular infiltration (arrowheads), irregular alveoli (a) and alveolar spaces (S) lined by few cells exhibiting flat nuclei (arrows). Note multiple extravasated RBCs (*) (H&E, ×100). (C) Section in the lung of a rat in amiodarone group showing over-distended alveoli (a) with disrupted alveolar walls (*). Note cellular infiltrates in the alveolar septa (arrowheads) (H&E, ×400).

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  Fig. 3. (A) Section in the lung of a rat in IVI stem cell therapy group showing two bronchioles (b), one of them demonstrates cellular infiltrate in the adventitia (arrowhead) and a congested vessel (c) (H&E, ×100). (B) Section in the lung of a rat in IVI stem cell therapy group showing a bronchiole (b), a vessel with partially thickened wall (v), congested vessels (c) and extravasated RBCs (*) (H&E, ×100). (C) Section in the lung of a rat in IVI stem cell therapy group showing normal alveoli (a) and alveolar sacs (S) lined by multiple cells exhibiting flat nuclei (arrows). Note cellular infiltrates (arrowheads) and extravasated RBCs in few alveolar septa (*) (H&E, ×400).

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  Fig. 4. (A) Section in the lung of a rat in IPI stem cell therapy group showing three normal bronchioles (b) surrounded by infiltrating cells (arrowheads) and two vessels (v) with partial thickening of their walls. Note some congested vessels (c) (H&E, ×100). (B) Section in the lung of a rat in IPI stem cell therapy group showing a normal bronchiole (b) surrounded by infiltrating cells (arrowheads) and two vessels (v) with marked thickening of their walls (v) (H&E, ×100). (C) Section in the lung of a rat in IPI stem cell therapy group showing normal alveoli (a) and alveolar sacs (S) lined by multiple cells exhibiting flat nuclei (arrows). Note cellular infiltrates (arrowheads) and extravasated RBCs in multiple alveolar septa (*) (H&E, ×400).

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  Fig. 5. (A) Section in the lung of a control rat showing fine collagen fibers (arrowheads) in the alveolar septa, denser collagen fibers in the wall of a bronchiole (arrows) and in the adventitia (*) of a blood vessel (Masson’s trichrome, ×400). (B) Section in the lung of a rat in amiodarone group showing dense collagen fibers (arrows) and infiltrating cells (arrowheads) in the alveolar septa (Masson’s trichrome, ×400). (C) Section in the lung of a rat in IVI stem cell therapy group showing dense collagen fibers (*) in a septum and infiltrating cells (arrowhead) in another septum around normal alveoli (a) and alveolar sacs (S) (Masson’s trichrome, ×400). (D) Section in the lung of a rat in IPI stem cell therapy group showing dense collagen fibers (arrows) in some septa and infiltrating cells (arrowheads) in other septa (Masson’s trichrome, ×400).

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  Fig. 6. (A) Section in the lung of a control rat showing negative staining in the alveoli (a), alveolar sacs (S) and alveolar septa (I) (Prussian blue, ×400). (B) Section in the lung of a rat in IVI stem cell therapy group showing multiple Prussian blue positive cells (arrows) inside and around blood vessels (v), in the alveolar septa (I) and among the epithelial lining of a bronchiole (b) (Prussian blue, ×400). (C) Section in the lung of a rat in IPI stem cell therapy group showing some Prussian blue positive cells (arrows) inside blood vessels (v), in the alveolar septa (I) and in the adventitia of a bronchiole (b) (Prussian blue, ×400).

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  Fig. 7. (A) Section in the lung of a control rat showing negative immunostaining in the alveoli (a), alveolar sacs (S) and alveolar septa (I) (CD105 immunostaining, ×400). (B) Section in the lung of a rat in IVI stem cell therapy group showing multiple CD105 positive cells (arrows) in the alveolar septa and among the lining epithelium of the alveoli and alveolar sacs (CD105 immunostaining, ×400). (C) Section in the lung of a rat in IPI stem cell therapy group showing some CD105 positive cells (arrows) in the alveolar septa and among the lining epithelium of the alveoli and alveolar sacs (CD105 immunostaining, ×400).

Reference

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