Summary Regenerative medicine opens new opportunities in the repair of cicatricial lesions of the vocal folds. Here, we present a thorough morphological study, with the focus on the collagen structures in the mucosa of the vocal folds, dedicated to the effects of stem cells on the vocal folds repair after cicatricial lesions. We used a conventional experimental model of a mature scar of the rabbit vocal folds, which was surgically excised with a simultaneous implantation of autologous bone marrow‐derived mesenchymal stem cells (MSC) into the defect. The restoration of the vocal folds was studied 3 months postimplantation of stem cells and 6 months after the first surgery. The collagen structure assessment included histology, immunohistochemistry and atomic force microscopy (AFM) studies. According to the data of optical microscopy and AFM, as well as to immunohistochemical analysis, MSC implantation into the vocal fold defect leads not only to the general reduction of scarring, normal ratio of collagens type I and type III, but also to a more complete restoration of architecture and ultrastructure of collagen fibres in the mucosa, as compared to the control. The collagen structures in the scar tissue in the vocal folds with implanted MSC are more similar to those in the normal mucosa of the vocal folds than to those of the untreated scars. AFM has proven to be an instrumental technique in the assessment of the ultrastructure restoration in such studies. Lay Description Regenerative medicine opens new opportunities in the repair of the vocal fold scars. Because collagen is a main component in the vocal fold mucosa responsible for the scar formation and repair, we focus on the collagen structures in the mucosa of the vocal folds, using a thorough morphological study based on histology and atomic force microscopy (AFM). Atomic force microscopy is a scanning microscopic technique which allows revealing the internal structure of a tissue with a resolution up to nanometres. We used a conventional experimental model of a mature scar of the rabbit vocal folds, surgically excised and treated with a mesenchymal stem cells transplant. Our morphological study, primarily AFM, explicitly shows that the collagen structures in the scarred vocal folds almost completely restore after the stem cell treatment. Thus, the modern microscopic methods, and especially AFM are instrumental tools for monitoring the repair of the vocal folds scars.

This review aims at becoming a guide which will help to plan the experimental design and to choose adequate methods to assess the outcomes when testing cell-based products in the treatment of the damaged vocal folds. The requirements to preclinical trials of cell-based products remain rather hazy and dictated by the country regulations. Most parameters like the way the cells are administered, selection of the cell source, selection of a carrier, and design of in vivo studies are decided upon by each research team and may differ essentially between studies. The review covers the methodological aspects of preclinical studies such as experimental models, characterization of cell products, assessment of the study outcome using molecular, morphological and immunohistochemical analyses, as well as measuring the tissue physical properties. The unified recommendations to perform preclinical trials could significantly facilitate the translation of cell-based products into the clinical practice. Graphical abstract

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The article is a brief review of publications devoted to the problem of persistent dysphonia. The main cause of voice disorders is the scarring of the vocal folds resulting from trauma, surgical manipulation, inflammatory process. Treatment of cicatricial lesions of the vocal folds remains a challenge, as far as existing methods do not ВведениеГолос -основной способ общения, необходимый для адаптации человека в окружающей среде и социаль-ной реализации. Нарушение голосовых функций имеет значительные негативные последствия не только для со-циальной и профессиональной сфер жизнедеятельности человека, но и для здоровья. Одной из самых частых при-чин расстройства дыхательной и фонаторной функций являются рубцовые изменения голосовых складок. Рубцы в гортани как исход неспецифической воспалительной реакции могут возникать в результате широкого спектра патологических процессов, таких как перенапряжение и неправильное голосоведение, острый или хронический ларингит, особенно в сочетании с рефлюксной болез-нью, ожог, тупая или острая травма гортани, включая ятрогенные повреждения при интубации. Хирургические операции, затрагивающие глубокие слои слизистой обо-лочки голосовых складок, также могут стать причиной формирования рубцов. Изменение структуры голосовых складок обусловливает нарушение их вибрации и сопро-вождается стойкими расстройствами голоса. S.M. Cohen и соавт. указывают на примерно одинаковую распростра-ненность дисфоний во всех странах, более высокую среди женщин (1,2 против 0,74% у мужчин). Средний возраст больных составляет 46,3 года.

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