Background and ObjectivesIdiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, invariably fatal fibrotic lung disease with no lasting option for therapy. Mesenchymal stem cells (MSCs) could be a promising modality for the treatment of IPF. Aim of the study was to investigate improvement in survivability and anti-fibrotic efficacy of human adipose-derived mesenchymal stem cells (AD-MSCs) in comparison with pirfenidone in the bleomycin-induced pulmonary fibrosis model.MethodsHuman AD-MSCs were administered intravenously on day 3, 6 and 9 after an intra-tracheal challenge with bleomycin, whereas, pirfenidone was given orally in drinking water at the rate of 100 mg/kg body weight three times a day daily from day 3 onward. AD-MSCs were labelled with PKH-67 before administration to detect engraftment. Disease severity and improvement was assessed and compared between sham control and vehicle control groups using Kaplan-Meier survival analysis, biochemical and molecular analysis, histopathology and high resolution computed tomography (HRCT) parameters at the end of study.ResultsResults demonstrated that AD-MSCs significantly increase survivability; reduce organ weight and collagen deposition better than pirfenidone group. Histological analyses and HRCT of the lung revealed that AD-MSCs afforded protection against bleomycin induced fibrosis and protect architecture of the lung. Gene expression analysis revealed that AD-MSCs potently suppressed pro-fibrotic genes induced by bleomycin. More importantly, AD-MSCs were found to inhibit pro-inflammatory related transcripts.ConclusionsOur results provided direct evidence that AD-MSC-mediated immunomodulation and anti-fibrotic effect in the lungs resulted in marked protection in pulmonary fibrosis, but at an early stage of disease.

Mesenchymal stem cells (MSC) are currently being evaluated in equine clinical studies for their potential to treat various disorders and injuries. Studies have shown that both autologous and allogeneic stem cells appear to be safe. However, an efficient cell expansion method that is reliable and cost-effective is warranted to provide off-the-shelf clinical grade stem cells. Our study aimed to determine optimum culture conditions for efficient large-scale stem cell expansion. We produced cGMP standard equine adipose derived mesenchymal stem cells on a large scale. Five different medium combinations-Dulbecco's modified Eagle's medium-knockout (DMEM-KO), alpha modified minimum essential medium (α-MEM), 50:50 DMEM-KO/α-MEM, 75:25 DMEM-KO/α-MEM and 25:75 DMEM-KO/α-MEM-at seeding densities of 1000, 2000, 3000, 4000 and 5000 cells/cm 2 , were used to determine the optimum culture conditions for large-scale production. Growth kinetics, immunophenotypes, karyotypes, morphology, trilineage differentiation, T-cell proliferation, virus positivity, pre-clinical toxicity and expression of pluripotency markers were analysed. Among the medium combinations and seeding densities tested, 25:75 DMEM-KO/α-MEM at a seeding density of 5000 cells/cm 2 was found to be optimum for large-scale expansion. This medium combination gave a significantly higher cell yield than the other medium combinations, while preserving their stem cell characteristics and differentiation potential. The results indicated that the adoption of an appropriate culture system significantly improved cell yield, thus enabling the production of sufficient cells for therapeutic application in a cost-effective manner. The results also showed that the method of large-scale expansion requires minimal manipulation of cells, and it could be expanded ex vivo within two passages while retaining the characteristics of true stem cells.

Low resistance motion of liquids on a well-defined path is beneficial for several MEMS based applications including energy harvesting and switching.By eliminating the contact line we demonstrate low resistance motion of a liquid bulge on pre-wetted strips. The bulge appears on wetted strips due to a morphological instability. The wetted strip confines the mercury bulge and defines its path of motion. Resistance to initiate motion of the bulge was studied experimentally and compared to other cases. An electret based energy harvesting device using bulge motion has been fabricated and tested.

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