Abstract
Aim:to perform a comparative analysis of the effi cacy of the inhaled and intravenous delivery of equivalent doses of bone marrow mesenchymal stem cells (BMMSCs) in rabbits according to the standard model of bleomycin pulmonary fi brosis.Materials and methods.After bronchoscopic instillation of bleomycin, 5 rabbits received intravenous transplantation of 2 × 106 allogeneic BMMSCs, other 5 rabbits – 2 × 107 MSCs inhaled via compressor nebulizer; control healthy and bleomycin group included 5 animals each.Results.Both groups treated with BMMSCs had a signifi cantly lower Ashcroft fi brosis index than the bleomycin control group. Expression of collagen in lung tissue in all groups with bleomycin injury was superior to healthy controls, but in animals underwent intravenous BMMSC transplantation collagen score was 0.74 points, and in inhaled treated group – 0.51 points, while in bleomycin controls – 2.1 point. Levels of TNF-α and TGF-β1 in BAL fl uids tended to decrease in treatment groups, but did not differ signifi cantly from control. A similar picture was observed in the cytological analysis of BAL.Conclusion.In general, both methods of delivering of BMMSCs to the lungs demonstrated similar therapeutic effects in inhibiting the development of experimental fi brosis, indicating that both intravenous and inhalational way of introduction can be used for subsequent clinical studies.
Highlights
Aim: to perform a comparative analysis of the efficacy of the inhaled and intravenous delivery of equivalent doses of bone marrow mesenchymal stem cells (BMMSCs) in rabbits according to the standard model of bleomycin pulmonary fibrosis
After bronchoscopic instillation of bleomycin, 5 rabbits received intravenous transplantation of 2 × allogeneic BMMSCs, other 5 rabbits – 2 × MSCs inhaled via compressor nebulizer; control healthy and bleomycin group included 5 animals each
Both groups treated with BMMSCs had a significantly lower Ashcroft fibrosis index than the bleomycin control group
Summary
Both groups treated with BMMSCs had a significantly lower Ashcroft fibrosis index than the bleomycin control group. Expression of collagen in lung tissue in all groups with bleomycin injury was superior to healthy controls, but in animals underwent intravenous BMMSC transplantation collagen score was 0.74 points, and in inhaled treated group – 0.51 points, while in bleomycin controls – 2.1 point. Both methods of delivering of BMMSCs to the lungs demonstrated similar therapeutic effects in inhibiting the development of experimental fibrosis, indicating that both intravenous and inhalational way of introduction can be used for subsequent clinical studies. Одним из перспективных подходов к лечению фиброзных заболеваний легких рассматривается трансплантация различных видов стволовых клеток (чаще мезенхимальных), которые за счет паракринных эффектов способны предотвратить или замедлить развитие фиброза в экспериментальных моделях [2,3,4]. Наша работа ставила задачу изучения эффектов аллогенных мезенхимальных стромальных клеток костного мозга (МСК) на модели легочного фиброза у более крупных животных – кроликов при разных путях доставки клеточного материала в легкие – ингаляционном и внутривенном
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