Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells

Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models. This body of work has provided evidence supporting clinical translational applications of adipose-derived cells in safety and efficacy trials. The present article reviews the case reports and phase I-III clinical evidence using autologous adipose-derived cells that have been published, to date, in the fields of gastroenterology, neurology, orthopedics, reconstructive surgery, and related clinical disciplines. Future directions and challenges facing the field are discussed and evaluated

Digital Signal Processing Reveals Circadian Baseline Oscillation in Majority of Mammalian Genes

In mammals, circadian periodicity has been described for gene expression in the hypothalamus and multiple peripheral tissues. It is accepted that 10%–15% of all genes oscillate in a daily rhythm, regulated by an intrinsic molecular clock. Statistical analyses of periodicity are limited by the small size of datasets and high levels of stochastic noise. Here, we propose a new approach applying digital signal processing algorithms separately to each group of genes oscillating in the same phase. Combined with the statistical tests for periodicity, this method identifies circadian baseline oscillation in almost 100% of all expressed genes. Consequently, circadian oscillation in gene expression should be evaluated in any study related to biological pathways. Changes in gene expression caused by mutations or regulation of environmental factors (such as photic stimuli or feeding) should be considered in the context of changes in the amplitude and phase of genetic oscillations

Pharmacokinetic pilot study of the antiangiogenic activity of standardized platycodi radix

Introduction: Platycodi radix is a radish used in food, such as Korean kimchi, and has been shown to cause weight loss in rodents. Platycodin D is considered its active ingredient and has been shown to inhibit lipases. The authors hypothesized that platycodi radix and the platycodin D it contains inhibit angiogenesis; another mechanism for weight loss. Methods: This study tested platycodi radix extract, platycodin D, and an extract of platycodi radix standardized to platycodin D for their ability to inhibit angiogenesis in a human adipose tissue assay. This study treated five healthy volunteers, orally, with platycodi radix extract standardized to 414 mg of platycodin D. Three volunteers were treated under fasting conditions, one volunteer with a 400 kcal meal, and one volunteer treated with a placebo. Blood was drawn over 5 hours to compare serum inhibition of the human adipose tissue angiogenesis. Results: Platycodin radix extract, platycodin D, and platycodi radix extract standardized to platycodin D all inhibited angiogenesis. The three volunteers who consumed platycodi radix extract standardized to 414 mg of platycodin D had a 25.76% reduction in angiogenesis from baseline at 60 minutes (P\u3c0.002), and had a statistically significant reduction in angiogenesis from 30 to 240 minutes (P\u3c0.05 to P\u3c0.002). The placebo decreased angiogenesis by 5.6% between 30 and 240 minutes, compared with 17.8% by the extract. The meal delayed absorption by approximately 3.5 hours. Conclusion: Platycodi radix extract standardized to platycodin D inhibited angiogenesis in human volunteers, and paves the way for a dose-response study and a human clinical obesity trial. © 2011 Springer Healthcare

Fine-Tuning Reception in the Bone: PPARγ and Company

PPARγ plays a central role in the formation of fat. Regulation of PPARγ activity depends on numerous factors ranging from dietary ligands to nuclear hormone coactivators and corepressors to oxygen-sensing mechanisms. In addition, the interplay of PPARγ with other nuclear hormone receptors has implications for the balance between adipogenesis and osteogenesis in mesenchymal stem cells of the bone marrow stroma. This review will explore a range of factors influencing PPARγ activity and how these interactions may affect osteogenesis

Permutation test for periodicity in short time series data

Abstract Background Periodic processes, such as the circadian rhythm, are important factors modulating and coordinating transcription of genes governing key metabolic pathways. Theoretically, even small fluctuations in the orchestration of circadian gene expression patterns among different tissues may result in functional asynchrony at the organism level and may contribute to a wide range of pathologic disorders. Identification of circadian expression pattern in time series data is important, but equally challenging. Microarray technology allows estimation of relative expression of thousands of genes at each time point. However, this estimation often lacks precision and microarray experiments are prohibitively expensive, limiting the number of data points in a time series expression profile. The data produced in these experiments carries a high degree of stochastic variation, obscuring the periodic pattern and a limited number of replicates, typically covering not more than two complete periods of oscillation. Results To address this issue, we have developed a simple, but effective, computational technique for the identification of a periodic pattern in relatively short time series, typical for microarray studies of circadian expression. This test is based on a random permutation of time points in order to estimate non-randomness of a periodogram. The Permutated time, or Pt-test, is able to detect oscillations within a given period in expression profiles dominated by a high degree of stochastic fluctuations or oscillations of different irrelevant frequencies. We have conducted a comprehensive study of circadian expression on a large data set produced at PBRC, representing three different peripheral murine tissues. We have also re-analyzed a number of similar time series data sets produced and published independently by other research groups over the past few years. Conclusion The Permutated time test (Pt-test) is demonstrated to be effective for detection of periodicity in short time series typical for high-density microarray experiments. The software is a set of C++ programs available from the authors on the open source basis.</p

Concise Review: Using Fat to Fight Disease: A Systematic Review of Nonhomologous Adipose‐Derived Stromal/Stem Cell Therapies

The objective of this Review is to describe the safety and efficacy of adipose stem/stromal cells (ASC) and stromal vascular fraction (SVF) in treating common diseases and the next steps in research that must occur prior to clinical use. Pubmed, Ovid Medline, Embase, Web of Science, and the Cochrane Library were searched for articles about use of SVF or ASC for disease therapy published between 2012 and 2017. One meta‐analysis, 2 randomized controlled trials, and 16 case series were included, representing 844 human patients. Sixty‐nine studies were performed in preclinical models of disease. ASCs improved symptoms, fistula healing, remission, and recurrence rates in severe cases of inflammatory bowel disease. In osteoarthritis, ASC and SVF improved symptom‐related, functional, radiographic, and histological scores. ASC and SVF were also shown to improve clinical outcomes in ischemic stroke, multiple sclerosis, myocardial ischemia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, chronic liver failure, glioblastoma, acute kidney injury, and chronic skin wounds. These effects were primarily paracrine in nature and mediated through reduction of inflammation and promotion of tissue repair. In the majority of human studies, autologous ASC and SVF from liposuction procedures were used, minimizing the risk to recipients. Very few serious, treatment‐related adverse events were reported. The main adverse event was postprocedural pain. SVF and ASC are promising therapies for a variety of human diseases, particularly for patients with severe cases refractory to current medical treatments. Further randomized controlled trials must be performed to elaborate potential safety and efficacy prior to clinical use. Stem Cells 2018;36:1311–1328Mesenchymal stem cells maintain homeostasis and may treat common diseases through homing, differentiation, and paracrine effects.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146316/1/stem2847_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146316/2/stem2847.pd

Competitive DNA transfection formulation via electroporation for human adipose stem cells and mesenchymal stem cells

<p>Abstract</p> <p>Background</p> <p>Adipose stem cells have a strong potential for use in cell-based therapy, but the current nucleofection technique, which relies on unknown buffers, prevents their use.</p> <p>Results</p> <p>We developed an optimal nucleofection formulation for human adipose stem cells by using a three-step method that we had developed previously. This method was designed to determine the optimal formulation for nucleofection that was capable of meeting or surpassing the established commercial buffer (Amaxa), in particular for murine adipose stem cells. By using this same buffer, we determined that the same formulation yields optimal transfection efficiency in human mesenchymal stem cells.</p> <p>Conclusions</p> <p>Our findings suggest that transfection efficiency in human stem cells can be boosted with proper formulation.</p