Bone marrow cells repair cigarette smoke-induced emphysema in rats

Abstract

The therapeutic potential of stem cells in chronic obstructive pulmonary disease is not well known although stem cell therapy is effective in models of other pulmonary diseases. We tested the capacities of bone marrow cells (BMCs), mesenchymal stem cells (MSCs), and conditioned media of MSCs (MSC-CM) to repair cigarette smoke-induced emphysema. Inbred female Lewis rats were exposed to cigarette smoke for 6 mo and then received BMCs, MSCs, or MSC-CM from male Lewis rats. For 2 mo after injection, the BMC treatment gradually alleviated the cigarette smoke-induced emphysema and restored the increased mean linear intercept. The BMC treatment significantly increased cell proliferation and the number of small pulmonary vessels, reduced apoptotic cell death, attenuated the mean pulmonary arterial pressure, and inhibited muscularization in small pulmonary vessels. However, only a few male donor cells were detected from 1 day to 1 mo after BMC administration. The MSCs and cell-free MSC-CM also induced the repair of emphysema and increased the number of small pulmonary vessels. Our data show that BMC, MSCs, and MSC-CM treatment repaired cigarette smoke-induced emphysema. The repair activity of these treatments is consistent with a paracrine effect rather than stem cell engraftment because most of the donor cells disappeared and because cell-free MSC-CM also induced the repair.

Mesenchymal stem cell-conditioned media recovers lung fibroblasts from cigarette smoke-induced damage

“…CSE was prepared as previously described (18,38). Briefly, 40 ml of cigarette smoke (Eighty Eight Light, containing 8.5 mg tar and 0.9 mg nicotine/cigarette; KT & G, Daejun, Korea) drawn into a 50-ml plastic syringe through a threeway cock was mixed with 10 ml of DMEM (Invitrogen) by vigorous shaking.…”

“…The animal experimental protocol was approved by the Institutional Animal Care and Use Committee of Asan Medical Center. MSC-CM was prepared from plastic-adherent rat MSCs, as in our previous report (18). In brief, following collection of bone marrow cells from femurs and tibias of 5-7-wk-old male Lewis rats, mononuclear cells were isolated by Percoll (Amersham, Piscataway, NJ) density gradient centrifugation (d ϭ 1.084).…”

“…Similarly, we recently reported that cell-free MSC-conditioned media (MSC-CM) is equipotent to MSCs in lung regeneration and increased formation of small pulmonary vessels, which is suggested as one of the reparative mechanisms in cigarette smoke-induced emphysema (18). However, even though vascular protective and angiogenic effects of conditioned media of stem cells have been proposed as one of the mechanisms for lung repair in animal models of emphysema (18,43) and bronchopulmonary dysplasia (4), effects of stem cell-conditioned media on lung fibroblasts have been barely demonstrated in the context of repair of lung damaged by cigarette smoke.…”

Extracellular Vesicles Derived from Gram-Negative Bacteria, such asEscherichia coli, Induce Emphysema Mainly via IL-17A–Mediated Neutrophilic Inflammation

“…In H&E-stained lung sections, the average (E) Cytokine levels in BAL fluid after the airway administration of E. coli EVs (1-, 10-, and 100-ng doses, respectively). interalveolar septal wall distance (mean linear intercept) was measured separately by two people in a blinded fashion (14).…”

Cell Therapy in Chronic Obstructive Pulmonary Disease: State of the Art and Perspectives

“…However, although the authors did not find evidence for an actual integration of MSC to the pulmonary tissue and the presence of cells with the pulmonary phenotype, there was demonstration that the SC transplant afforded a decrease in the lungs inflammation and edema induced by the LPS. There are, accordingly these results, the indication that the action mechanism of cells would be mediated by paracrine factors that stimulate tissue regeneration rather than cell engraftment into lungs (Huh et al, 2011).…”