Regulation of transplanted mesenchymal stem cells by the lung progenitor niche in rats with chronic obstructive pulmonary disease

Abstract

BackgroundStem cell transplantation is a promising method for the treatment of chronic obstructive pulmonary disease (COPD), and mesenchymal stem cells (MSCs) have clinical potential for lung repair/regeneration. However, the rates of engraftment and differentiation are generally low following MSC therapy for lung injury. In previous studies, we constructed a pulmonary surfactant-associated protein A (SPA) suicide gene system, rAAV-SPA-TK, which induced apoptosis in alveolar epithelial type II (AT II) cells and vacated the AT II cell niche. We hypothesized that this system would increase the rates of MSC engraftment and repair in COPD rats.MethodsThe MSC engraftment rate and morphometric changes in lung tissue in vivo were investigated by in situ hybridization, hematoxylin and eosin staining, Masson’s trichrome staining, immunohistochemistry, and real-time PCR. The expression of hypoxia inducible factor (HIF-1α) and stromal cell-derived factor-1 (SDF-1), and relationship between HIF-1α and SDF-1 in a hypoxic cell model were analyzed by real-time PCR, western blotting, and enzyme-linked immunosorbent assay.ResultsrAAV-SPA-TK transfection increased the recruitment of MSCs but induced pulmonary fibrosis in COPD rats. HIF-1α and SDF-1 expression were enhanced after rAAV-SPA-TK transfection. Hypoxia increased the expression of HIF-1α and SDF-1 in the hypoxic cell model, and SDF-1 expression was augmented by HIF-1α under hypoxic conditions.ConclusionsVacant AT II cell niches increase the homing and recruitment of MSCs to the lung in COPD rats. MSCs play an important role in lung repair and promote collagen fiber deposition after induction of secondary damage in AT II cells by rAAV-SPA-TK, which involves HIF-1α and SDF-1 signaling.

The role of osmolality in saline fluid nebulization after tracheostomy: time for changing?

“…A 0.5 cm long sample of tracheal tissue was excised nearly from the 0.3 to 0.8 com trachea portion lower the stoma, and was fixed in 2.5% glutaraldehyde for 24 h, the specimens were dehydrated and then embedded in paraffin, finally the transverse section of specimens were sliced for HE staining as previously described [19, 20], each tissue section was examined and photopgraphed using an Olympus light microscope (Olympus OX51), Image J software (US National Institutes of Health, Bethesda, MD, USA) was used to calculate the white blood cell counts, we tended to quantify the disarrangement of mucosal epithelium or basement membrane yet no accurate method to resort.…”

Development and characterization of a naturally derived lung extracellular matrix hydrogel

“…MSCs have been successfully delivered in solution as a therapy for acute lung injury in several models . Despite their success these therapies have failed to produce significant improvement when addressing chronic lung pathologies due to the low retention in the tissue over time . Cell delivery strategies for encapsulating and maintaining the therapeutic efficacy of the dosed cells have been developed from both natural and synthetic materials .…”

Optimal Dose and Timing of Umbilical Stem Cells Treatment in Pulmonary Arterial Hypertensive Rats

“…A number of studies demonstrated the efficacy of mesenchymal stem cell administration in many lung diseases including acute lung injury,8 bronchopulmonary dysplasia,910 chronic obstructive pulmonary disease,1112 fibrosing pulmonary injury,1314 pulmonary ischemia reperfusion injury,15 radiation induced lung injury,16 sepsis,17 and PAH 7918. Mesenchymal stem cells have an effect on lung inflammation and injury through paracrine interactions rather than direct interaction.…”