Strong A.L.,Tulane University |
Burow M.E.,Tulane University |
Gimble J.M.,Tulane University |
Bunnell B.A.,Tulane University |
Bunnell B.A.,Lacell, Llc
Stem Cells | Year: 2015
With the recognition of obesity as a global health crisis, researchers have devoted greater effort to defining and understanding the pathophysiological molecular pathways regulating the biology of adipose tissue and obesity. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, has been linked to an increased incidence and aggressiveness of colon, hematological, prostate, and postmenopausal breast cancers. The increased morbidity and mortality of obesity-associated cancers have been attributed to higher levels of hormones, adipokines, and cytokines secreted by the adipose tissue. The increased amount of adipose tissue also results in higher numbers of adipose stromal/stem cells (ASCs). These ASCs have been shown to impact cancer progression directly through several mechanisms, including the increased recruitment of ASCs to the tumor site and increased production of cytokines and growth factors by ASCs and other cells within the tumor stroma. Emerging evidence indicates that obesity induces alterations in the biologic properties of ASCs, subsequently leading to enhanced tumorigenesis and metastasis of cancer cells. This review will discuss the links between obesity and cancer tumor progression, including obesity-associated changes in adipose tissue, inflammation, adipokines, and chemokines. Novel topics will include a discussion of the contribution of ASCs to this complex system with an emphasis on their role in the tumor stroma. The reciprocal and circular feedback loop between obesity and ASCs as well as the mechanisms by which ASCs from obese patients alter the biology of cancer cells and enhance tumorigenesis will be discussed. © 2014 AlphaMed Press.
Tran T.D.N.,Louisiana State University |
Gimble J.M.,Lacell, Llc |
Cheng H.,Louisiana State University
Cell Calcium | Year: 2016
Intracellular Ca2+ signals are essential for stem cell differentiation due to their ability to control signaling pathways involved in this process. Arginine vasopression (AVP) is a neurohypophyseal hormone that increases intracellular Ca2+ concentration during adipogenesis via V1a receptors, Gq-proteins and the PLC-IP3 pathway in human adipose-derived stromal/stem cells (hASCs). These Ca2+ signals originate through calcium release from pools within the endoplasmic reticulum and the extracellular space. AVP supplementation to the adipogenic media inhibits adipogenesis and key adipocyte marker genes. This review focuses on the intersection between AVP, Ca2+ signals and ASC differentiation. © 2016 Elsevier Ltd.
Davis T.A.,Naval Medical Research Center |
Davis T.A.,Uniformed Services University of the Health Sciences |
Anam K.,Naval Medical Research Center |
Lazdun Y.,Naval Medical Research Center |
And 4 more authors.
Stem Cells Translational Medicine | Year: 2014
Amputations and unsalvageable injuries with devastating tissue loss are common in the combat wounded. Reconstructive transplantation in the civilian setting using vascular composite allotrans-plants (VCAs) with multiple tissues (skin, muscle, nerve, bone) combined with long-term multidrug im-munosuppression has been encouraging. However, skin rejection remains a critical complication. Adipose-derivedstromal/stemcells(ASCs)are easily obtained from normal individuals in high numbers, precluding ex vivo expansion. The reparative function and paracrine immunomodulatory capacity of ASCs has gained considerable attention. The present study investigated whether ASCs facilitate long-term skin allograft survival. ASCs were isolated from fresh human subcutaneous adipose lipoas-pirate. Full-thickness skin grafts from BALB/c mice were transplanted onto the dorsal flanks of C57BL/6 mice treated with five doses of anti-CD4/CD8 monoclonal antibodies (10 mg/kg) on days 0, +2, +5, +7, and +14 relative to skin grafting. A single nonmyeloablative low dose of busulfan(5mg/kg) was given on day +5. Seven days after skin transplantation, ASCs (3 × 106) were infused i.v. with or without donor bone marrow cells (BMCs; 5 × 105). ASC+BMC coinfusion with minimal conditioning led to stable lym-phoid and myeloid macrochimerism, deletionof alloreactive T cells, expansion of regulatory Tcells, and long-term allograft survival (>200 days). ASCs constitutively produced high levels ofanti-inflammatory/ immunoregulatory factors such as prostaglandin E2, indoleamine 2,3-dioxygenase, APO-1/Fas (CD95), and programmed cell death-1 ligand-2. These findings serve as a foundation for developing a translational advanced VCA protocol, embodying both ASCs and low-dose donor BMCs, in nonhuman primates, with the goal of enhancing functional outcomes and eliminating the complications associated with long-term immunosuppression. ©AlphaMed Press.
Yilgor Huri P.,Johns Hopkins University |
Cook C.A.,Johns Hopkins University |
Hutton D.L.,Johns Hopkins University |
Goh B.C.,Johns Hopkins University |
And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2013
Adipose-derived stem/stromal cell (ASC)-based tissue engineered muscle grafts could provide an effective alternative therapy to autografts - which are limited by their availability - for the regeneration of damaged muscle. However, the current myogenic potential of ASCs is limited by their low differentiation efficiency into myoblasts. The aim of this study was to enhance the myogenic response of human ASCs to biochemical cues by providing biophysical stimuli (11% cyclic uniaxial strain, 0.5. Hz, 1. h/day) to mimic the cues present in the native muscle microenvironment. ASCs elongated and fused upon induction with myogenic induction medium alone. Yet, their myogenic characteristics were significantly enhanced with the addition of biophysical stimulation; the nuclei per cell increased approximately 4.5-fold by day 21 in dynamic compared to static conditions (23.3 ± 7.3 vs. 5.2 ± 1.6, respectively), they aligned at almost 45° to the direction of strain, and exhibited significantly higher expression of myogenic proteins (desmin, myoD and myosin heavy chain). These results demonstrate that mimicking the biophysical cues inherent to the native muscle microenvironment in monolayer ASC cultures significantly improves their differentiation along the myogenic lineage. © 2013 Elsevier Inc.
Sonnier T.,Pennington Biomedical Research Center |
Rood J.,Pennington Biomedical Research Center |
Gimble J.M.,Pennington Biomedical Research Center |
Gimble J.M.,Tulane University |
And 2 more authors.
Journal of Diabetes and its Complications | Year: 2014
Aims: Recent studies suggest that circadian rhythms regulate glucose metabolism, weight loss, and even drug efficacy. Moreover, molecules targeted at the circadian clock show promise in treating metabolic disease. Therefore, this study set out to better characterize interactions among diurnal rhythms in prediabetes.Methods: Ten subjects with prediabetes completed oral glucose tolerance tests at 0700 h and 1900 h on the same day. Lipids and hormones were also measured.Results: Two-hour and three-hour glucose tolerances were worse in the evening by 40 ± 52 mg/dl (p = 0.02) and 62 ± 46 mg/dl (p = 0.001), respectively. These impairments were explained by lower insulin sensitivity (OGIS; 5.14 ± 1.02 vs. 4.74 ± 0.77 mg/kg/min; p = 0.03) and 2-hour AUC insulin levels (87.4 ± 37.6 vs. 69.8 ± 40.2 mU·hr/l; p = 0.02) in the evening. Intriguingly, more insulin resistant subjects had weaker rhythms in insulin sensitivity (r = - 0.66; p = 0.04) but enhanced rhythms in insulin (r = - 0.67; p = 0.03) and cortisol (r = - 0.78; p = 0.008) levels. Importantly, the rhythms in cortisol primarily but also insulin sensitivity drove the declines in evening glucose tolerance (r = 0.86; p = 0.002).Conclusions: Glycemic control is dramatically impaired in the evening in people with prediabetes, particularly when the cortisol rhythm is weak, but is unrelated to the rhythm in insulin levels. Therefore, food intake at dinnertime may need to be curbed in prediabetes. © 2014 Elsevier Inc. All rights reserved.