Intraperitoneal adoptive transfer of mesenchymal stem cells enhances recovery from acid aspiration acute lung injury in mice

Abstract

BackgroundMesenchymal stem cells (MSCs) might act as fine-tuners of inflammation during acute lung injury. We assessed the effects of adoptive transfer of MSCs in acid aspiration acute lung injury and explored the role of long pentraxin PTX3.MethodsWe conducted a prospective experimental interventional study on wild-type (WT) and PTX3-deficient (PTX3−/−) mice. Acute lung injury was induced in WT and PTX3−/− mice by instillation of hydrochloric acid into the right bronchus. One hour later, animals received intraperitoneal sterile phosphate-buffered saline (PBS), WT-MSCs (1 × 106) or PTX3−/−-MSCs (1 × 106). Twenty-four hours after injury, we measured the effects of treatments on arterial blood gases, wet/dry lung weight (W/D), CT scan analysis of lung collapse, neutrophils, TNFα and CXCL1 in bronchoalveolar lavage, and plasma PTX3. d-dimer was assayed in 1 week and OH-proline in 2 weeks to track the fibrotic evolution.ResultsIn 24 h, in comparison to PBS, WT-MSCs improved oxygenation and reduced W/D and alveolar collapse. These effects were associated with decreased concentrations of alveolar neutrophils and cytokines. WT-MSCs increased d-dimer concentration and decreased OH-proline levels, too.Treatment with PTX3−/−-MSCs ameliorated oxygenation, W/D, and alveolar TNFα, though to a lesser extent than WT-MSCs. PTX3−/−-MSCs did not improve lung collapse, neutrophil count, CXCL1, d-dimer, and OH-proline concentrations. The protective effects of WT-MSCs were dampened by lack of endogenous PTX3, too.ConclusionsIn acid aspiration acute lung injury, MSCs improve pulmonary function and limit fibrosis by fine-tuning inflammation. The role of PTX3 in determining MSCs’ effects might merit further scrutiny.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-017-0126-5) contains supplementary material, which is available to authorized users.

The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer

“…Similar results were obtained in a mouse model of acid aspiration-dependent acute lung injury (69), mimicking acute respiratory distress syndrome (ARDS) caused by aspiration of gastric contents (99). In the mouse model, beneficial effects of treatment with MSCs on the early acute inflammatory reaction, pulmonary edema and long-term fibrotic evolution and pulmonary function have been observed.…”

“…In different mouse models of non-infectious tissue damage, deficiency of the long pentraxin PTX3 was associated with altered thrombotic response to the lesion, increased deposition and persistence of fibrin, followed by increased collagen deposition (15, 62, 67–69) (Figure 3).…”

Porcine Wharton’s jelly cells distribute throughout the body after intraperitoneal injection

“…Our results contrast with the report of Bazhanov et al [ 8 ] who found that human bone marrow-derived MSCs appeared to aggregate with macrophages and B220 + lymphocytes in the peritoneal cavity of mice and did not reach other sites. Perhaps consistent with Bazhanov et al, Mauri et al [ 20 ] transplanted bone marrow-derived mouse MSCs into mice and did not detect the IP injected MSCs in the lungs, spleen, or liver 24 h after injection. They did, however, demonstrate improvement in lung functions in the transplanted mice after acute injury, and thus effects could have been due to paracrine mechanisms.…”

Pentraxin 3 and its role in tissue repair

“…W mysich modelach niezakaźnego uszkodzenia tkanki, niedobór długiej pentraksyny związany był ze zmienioną odpowiedzią zakrzepową, zwiększonym odkładaniem fibryny, po którym następowało zwiększone odkładanie się kolagenu [8,18,23,24]. Na skutek uszkodzenia tkanki następowało indukowanie miejscowego wydzielania PTX3.…”

“…Poziomy D-dimerów znacznie zwiększyły się u myszy po leczeniu komórkami MSCs bogatymi w PTX3, co wskazuje na zdolność komórek macierzystych do modulowania fibrynolizy płucnej i, w rezultacie, wpływania na bliznowacenie włókniste. Podanie MSCs ubogich w PTX3 skutkowało zmniejszonym stężeniem D dimerów w płucach w porównaniu do MSCs bogatych w PTX3, co nadawało nieprawidłowej fibrynolizie obserwowany, zmniejszony efekt terapeutyczny komórek MSC ubogich w PTX3 [24].…”