Regenerative medicine approaches for the management of respiratory tract fistulas

Trivisonno, Angelo; Nachira, Dania; Boškoski, Ivo; Porziella, Venanzio; Rocco, Giuliana Di; Baldari, Silvia; Toietta, Gabriele

doi:10.1186/s13287-020-01968-1

Cited by 14 publications

(6 citation statements)

References 113 publications

(146 reference statements)

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“…A respiratory tract fistula is an abnormal passage communicating between any component of the respiratory tract or between any part of the respiratory system and surrounding organs [1], including tracheal fistula (TF) and bronchial fistula (BF). Tracheal fistula includes tracheoesophageal fistula (TEF) and tracheomediastinal fistula (TMF).…”

Section: Introductionmentioning

confidence: 99%

The therapeutic effect of stem cells from human exfoliated deciduous teeth on a rat model of tracheal fistula

Wang

Lyu

et al. 2022

Stem Cell Res Ther

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Background Tracheal fistulas (TF) can be dangerous and even fatal in patients. The current treatment is really challenging. Previous studies reported that mesenchymal stem cells (MSCs) could be used to treat respiratory tract fistulas. Stem cells from human exfoliated deciduous teeth (SHED) are considered to be MSC-like cells that may also have the potential to treat the tracheal fistulas. In this study, we investigated the therapeutic effects of SHED in rat tracheal fistula models. Methods A total of 80 SD rats were randomly divided into five groups: a sham-operated group, a local PBS group (L-PBS), an intravenous PBS group (I-PBS), a local SHED treatment group (L-SHED), and an intravenous SHED treatment group (I-SHED). The L-SHED and I-SHED groups were given a topical application around the fistula or an intravenous injection of 1*107 SHED via the tail vein, respectively, while the L-PBS and I-PBS groups were given an equivalent volume of PBS through local or intravenous administration. A stereomicroscope was used to observe fistula healing on the 2nd, 3rd, and 5th days following transplantation. On the 7th day, the survival of SHED was observed by immunofluorescence. The pathology of the lungs and fistulas was observed by hematoxylin and eosin (H&E) and Masson staining. The expression levels of the Toll-like receptor 4 (TLR4), interleukin (IL)-1β, IL-33, and IL-4 were measured using immunohistochemistry. The expression levels of TLR4, high mobility group box 1 (HMGB1), and myeloid differentiation factor 88 (MYD88) were studied using western blotting. On day 14, airway responsiveness of rats was detected and analyzed. Results Fistula healing in the L-SHED and I-SHED groups was faster than that in their respective PBS groups after transplantation. The fistula diameters in the L-SHED and I-SHED groups were significantly smaller than those in the L-PBS and I-PBS groups on the 3rd day. Moreover, the phenomenon of fibroblast proliferation and new blood vessel growth around the fistula seemed more pronounced in the L-SHED and I-SHED groups. Although no discernible difference was found in airway responsiveness after SHED treatment, the degree of inflammation in the lungs was reduced by intravenous SHED treatment. However, there was no significant reduction in lung inflammation by local SHED treatment. The expression levels of IL-1β and IL-33 were decreased in the I-SHED group, while IL-4 was elevated compared with the I-PBS group. Interestingly, intravenous SHED treatment inhibited the activation of HMGB1/TLR4/MYD88 in the lung tissues of TF rats. Conclusions SHED transplantation accelerated the rate of fistula healing in rats. Intravenous SHED treatment reduced lung inflammation. Thus, SHED may have potential in the treatment of tracheal fistula, providing hope for future therapeutic development for TF.

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Section: Introductionmentioning

confidence: 99%

The therapeutic effect of stem cells from human exfoliated deciduous teeth on a rat model of tracheal fistula

Wang

Lyu

et al. 2022

Stem Cell Res Ther

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“…По мнению многих авторов, снизить риск развития бронхоплевральных свищей можно за счет улучшения васкуляризации культи. Применение клеточной терапии, в основе которой лежит стимуляция регенеративных процессов, в том числе и неоангиогенеза, должно будет оказывать положительный эффект на культю бронха [12].…”

Section: Introductionunclassified

Possibilities of cell therapy in thoracic surgery

Polyakov,

Porhanov,

Kovalenko

et al. 2023

The Scientific Notes of the Pavlov university

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Introduction. Bronchial fistula often occurs after lung surgery. This is an extremely severe complication with high mortality. Despite the variety methods for the treatment of bronchial fistula, the results are not always effective. In our paper, we presented a method of preventing the development of bronchial fistula based on the cell therapy. The objective of the study was to evaluate the effects of the cell therapy on the regeneration of damaged bronchial tissue in an experiment on non-human primates. Methods and materials. The study was performed on 6 non-human primates. Laboratory animals were divided into 2 groups: experimental and control. The left pneumonectomy with the formation of a stump of the main bronchus was done in each primate. In the experimental group, a regenerative product was introduced into the stump; in the control group, 0.9 % NaCl solution was used. The regenerative product consisted of autologous platelet-rich plasma activated by thermal lysis and the suspension of the xenogeneic fibroblast’s culture. The primates were observed for 7, 14 and 21 days, the peripheral blood was taken to study the dynamics of biologically active substances. A histological examination of the autopsy material was performed at the end of the follow-up time. Results. On the early postoperative period, a typical inflammatory reaction was observed and resulted by the intraoperative tissue damage. Then the morphological changes were different in both group. The inflammatory were mild, the restoration of the natural function of the mucous membrane and the formation of scar tissue were earlier in the experimental group than in the control group. An analysis of the dynamics of plasma mediators in the postoperative period revealed an earlier dominance of regenerative processes in the experimental group. Conclusion. The results of the study showed that the cell therapy stimulates the tissue regeneration, thereby preventing the failure of the bronchial stump suture.

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“…По данным нашего центра, в послеоперационном периоде свищи развиваются в 2,4% случаев. Основные причины развития бронхоплевральных свищей (БС) -пневмонэктомия и лобэктомия [2,3,5,6]. Другими причинами являются пневмония, которая может привести к некрозу стенки бронха, пневмоторакс, химиотерапия и радиотерапия при онкологии, а также туберкулез [2,5].…”

Section: Introductionunclassified

“…Кроме того, химиолучевая и/или антиангиогенная терапия, воздействуя на локальные изменения архитектоники сосудистой ткани, могут увеличить риск формирования свищей. Как правило, ТПС осложняются инфекционными процессами и практически всегда требуют оперативного вмешательства [5,13].…”

Section: Introductionunclassified

Cell Therapy for Upper Respiratory Tract Fistulas

Polyakov,

Porhanov,

Kovalenko

et al. 2023

Innovacionnaâ medicina Kubani

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Fistulas of various etiologies are one of the severe and life-threatening diseases of the upper respiratory tract. The most common cause is bronchial stump failure after pulmonary resection, usually pneumonectomy. The incidence and mortality of this complication is 3 %-4 % and 12.5 %-71.2 %, respectively. Despite the fact that many devices and methods have been described to date, it is usually treated with surgical closure. Standard surgical approaches are associated with significant morbidity and mortality and are not reliably successful. In recent years, cell therapies aimed to stimulate tissue healing rose to prominence and can be considered a potential treatment method. We review current trends in bronchopleural fistula treatment using cell therapy and report cases of the bronchopleural fistula treatment according to the research protocol developed in our clinic. Although clinical experience is quite limited owing to a small number of patients in the most studies, the information on safety and tolerance can help plan future larger trials with innovative methods to further improve clinical results.

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Regenerative medicine approaches for the management of respiratory tract fistulas

Cited by 14 publications

References 113 publications

The therapeutic effect of stem cells from human exfoliated deciduous teeth on a rat model of tracheal fistula

The therapeutic effect of stem cells from human exfoliated deciduous teeth on a rat model of tracheal fistula

Possibilities of cell therapy in thoracic surgery

Cell Therapy for Upper Respiratory Tract Fistulas

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