Previous phase I studies demonstrated safety and some beneficial effects of mesenchymal stem cells (MSCs) in patients with mild to moderate idiopathic pulmonary fibrosis (IPF). The aim of our study was to evaluate the safety, tolerability, and efficacy of a high cumulative dose of bone marrow MSCs in patients with rapid progressive course of severe to moderate IPF. Twenty patients with forced ventilation capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide (DLCO) ≥20% with a decline of both >10% over the previous 12 months were randomized into two groups: one group received two intravenous doses of allogeneic MSCs (2 × 10 8 cells) every 3 months, and the second group received a placebo. A total amount of 1.6 × 10 9 MSCs had been administered to each patient after the study completion. There were no significant adverse effects after administration of MSCs in any patients. In the group of MSC therapy, we observed significantly better improvement for the 6-minute walk distance in 13 weeks, for DLCO in 26 weeks, and for FVC in 39 weeks compared with placebo.FVC for 12 months in the MSCs therapy group increased by 7.8% from baseline, whereas it declined by 5.9% in the placebo group. We did not find differences between the groups in mortality (two patients died in each group) or any changes in the high-resolution computed tomography fibrosis score. In patients with IPF and a rapid pulmonary function decline, therapy with high doses of allogeneic MSCs is a safe and promising method to reduce disease progression.

Phytosterols are plant sterols found in foods such as oils, nuts and vegetables. Phytosterols, in the same way as cholesterol, contain a double bond and are susceptible to oxidation. The objective of the present study was to assess the potential toxic effects of b-sitosterol oxides on U937 cells. The effects of increasing concentrations (0-120 mM) of b-sitosterol oxides on cellular cytotoxicity, apoptosis, antioxidant status and genotoxicity was assessed over 12, 24 and 48 h exposure periods. Following 12 h, the viability of cells treated with 120 mM-b-sitosterol oxides was reduced to 51·7 % relative to control. At 24 and 48 h, both 60 and 120 mM-b-sitosterol oxides caused a significant decrease in cell viability. For comparison, a decrease in viability of cells treated with a cholesterol oxide, 7b-hydroxycholesterol (7b-OH, 30 mM), was evident at 24 h. An increase in apoptotic cells, assessed using Hoechst 33342, indicates that the mode of cell death in U937 cells following exposure to 7b-OH (30 mM) and b-sitosterol oxides (60 and 120 mM) was by apoptosis. The increase in apoptotic cells after 12 h following treatment with 120 mM-b-sitosterol oxides was accompanied by a decrease in cellular glutathione. Similarly, 7b-OH (30 mM) treatment resulted in decreased glutathione at 12 h. Catalase activity was not affected by any of the treatments. b-Sitosterol oxides had no genotoxic effects on U937 and V79 cells as assessed by the comet and sister chromatid exchange assays respectively. In general, the results indicate that thermally oxidised derivatives of b-sitosterol demonstrate similar biological effects as 7b-OH in U937 cells, but at higher concentrations.

Stem cells provide an alternative curative intervention for the infarcted heart by compensating for the cardiomyocyte loss subsequent to myocardial injury. The presence of resident stem and progenitor cell populations in the heart, and nuclear reprogramming of somatic cells with genetic induction of pluripotency markers are the emerging new developments in stem cell-based regenerative medicine. However, until safety and feasibility of these cells are established by extensive experimentation in in vitro and in vivo experimental models, skeletal muscle-derived myoblasts, and bone marrow cells remain the most well-studied donor cell types for myocardial regeneration and repair. This article provides a critical review of skeletal myoblasts as donor cells for transplantation in the light of published experimental and clinical data, and indepth discussion of the advantages and disadvantages of skeletal myoblast-based therapeutic intervention for augmentation of myocardial function in the infarcted heart. Furthermore, strategies to overcome the problems of arrhythmogenicity and failure of the transplanted skeletal myoblasts to integrate with the host cardiomyocytes are discussed. Keywordsheart; myoblast; myocardium; stem cell Despite the advances in medical and surgical treatment of myocardial infarction, ischemic heart disease remains the leading cause of morbidity and mortality on a global scale [1]. The gravity of the problem can be assessed by the fact that mortality from ischemic heart disease exceeds the mortality from cancer -as the 1-year survival rate is lower than 50%. The immune and inflammatory responses following myocardial infarction are characterized by neutrophil and macrophage accumulation, cytokine secretion, recruitment of T and B cells, and formation of antibodies specific to myosin and actin [2]. The successive biochemical, structural and functional adaptive changes in the infarcted and hibernating myocardium lead to expansion of the infarction zone and scarring, while the hibernating myocardium in the periphery of the infarct become hypertrophic. The hearts of patients who survive the acute phase of myocardial infarction subsequently enter into a vicious cycle of left ventricular remodeling as part of the compensatory mechanism caused by the massive loss of functioning cardiomyocytes. Various therapeutic options including pharmacotherapeutic intervention (e.g., angiotensin-converting enzyme inhibitors, β-blockers, diuretics and angiotensin receptors blockers) are available but only provide a symptomatic relief without † Author for correspondence: Tel.: +1 513 558 0145, haiderkh@ucmail.uc.edu. Financial & competing interests disclosureThe authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. addressing the fundamental issue of myoc...

We have designed a novel two-component matrix (SPRPix) for the encapsulation of directly reprogrammed human neural precursor cells (drNPC). The matrix is comprised of 1) a solid anisotropic complex scaffold prepared by electrospinning a mixture of recombinant analogues of the spider dragline silk proteins – spidroin 1 (rS1/9) and spidroin 2 (rS2/12) - and polycaprolactone (PCL) (rSS-PCL), and 2) a “liquid matrix” based on platelet-rich plasma (PRP). The combination of PRP and spidroin promoted drNPC proliferation with the formation of neural tissue organoids and dramatically activated neurogenesis. Differentiation of drNPCs generated large numbers of βIII-tubulin and MAP2 positive neurons as well as some GFAP-positive astrocytes, which likely had a neuronal supporting function. Interestingly the SPRPix microfibrils appeared to provide strong guidance cues as the differentiating neurons oriented their processes parallel to them. Implantation of the SPRPix matrix containing human drNPC into the brain and spinal cord of two healthy Rhesus macaque monkeys showed good biocompatibility: no astroglial and microglial reaction was present around the implanted construct. Importantly, the human drNPCs survived for the 3 month study period and differentiated into MAP2 positive neurons. Tissue engineered constructs based on SPRPix exhibits important attributes that warrant further examination in spinal cord injury treatment.