Browsing by Subject "Adipose Tissue"

Now showing 1 - 11 of 11

Open Access
Bulbar muscle weakness and fatty lingual infiltration in glycogen storage disorder type IIIa.
(Molecular genetics and metabolism, 2012-11) Horvath, Jeffrey J; Austin, Stephanie L; Jones, Harrison N; Drake, Elizabeth J; Case, Laura E; Soher, Brian J; Bashir, Mustafa R; Kishnani, Priya S
Glycogen storage disorder type III (GSD III) is a rare autosomal recessive disorder resulting from a deficiency of glycogen debranching enzyme, critical in cytosolic glycogen degradation. GSD IIIa, the most common form of GSD III, primarily affects the liver, cardiac muscle, and skeletal muscle. Although skeletal muscle weakness occurs commonly in GSD IIIa, bulbar muscle involvement has not been previously reported. Here we present three GSD IIIa patients with clinical evidence of bulbar weakness based on instrumental assessment of lingual strength. Dysarthria and/or dysphagia, generally mild in severity, were evident in all three individuals. One patient also underwent correlative magnetic resonance imaging (MRI) which was remarkable for fatty infiltration at the base of the intrinsic tongue musculature, as well as abnormal expansion of the fibro-fatty lingual septum. Additionally, we provide supportive evidence of diffuse glycogen infiltration of the tongue at necropsy in a naturally occurring canine model of GSD IIIa. While further investigation in a larger group of patients with GSD III is needed to determine the incidence of bulbar muscle involvement in this condition and whether it occurs in GSD IIIb, clinical surveillance of lingual strength is recommended.
Open Access
C1q/Tumor Necrosis Factor-Related Protein-9 Regulates the Fate of Implanted Mesenchymal Stem Cells and Mobilizes Their Protective Effects Against Ischemic Heart Injury via Multiple Novel Signaling Pathways.
(Circulation, 2017-11) Yan, Wenjun; Guo, Yongzhen; Tao, Ling; Lau, Wayne Bond; Gan, Lu; Yan, Zheyi; Guo, Rui; Gao, Erhe; Wong, G William; Koch, Walter L; Wang, Yajing; Ma, Xin-Liang
Background
Cell therapy remains the most promising approach against ischemic heart injury. However, the poor survival of engrafted stem cells in the ischemic environment limits their therapeutic efficacy for cardiac repair after myocardial infarction. CTRP9 (C1q/tumor necrosis factor-related protein-9) is a novel prosurvival cardiokine with significantly downregulated expression after myocardial infarction. Here we tested a hypothesis that CTRP9 might be a cardiokine required for a healthy microenvironment promoting implanted stem cell survival and cardioprotection.
Methods
Mice were subjected to myocardial infarction and treated with adipose-derived mesenchymal stem cells (ADSCs, intramyocardial transplantation), CTRP9, or their combination. Survival, cardiac remodeling and function, cardiomyocytes apoptosis, and ADSCs engraftment were evaluated. Whether CTRP9 directly regulates ADSCs function was determined in vitro. Discovery-drive approaches followed by cause-effect analysis were used to uncover the molecular mechanisms of CTRP9.
Results
Administration of ADSCs alone failed to exert significant cardioprotection. However, administration of ADSCs in addition to CTRP9 further enhanced the cardioprotective effect of CTRP9 (P<0.05 or P<0.01 versus CTRP9 alone), suggesting a synergistic effect. Administration of CTRP9 at a dose recovering physiological CTRP9 levels significantly prolonged ADSCs retention/survival after implantation. Conversely, the number of engrafted ADSCs was significantly reduced in the CTRP9 knockout heart. In vitro study demonstrated that CTRP9 promoted ADSCs proliferation and migration, and it protected ADSCs against hydrogen peroxide-induced cellular death. CTRP9 enhances ADSCs proliferation/migration by extracellular regulated protein kinases (ERK)1/2-matrix metallopeptidase 9 signaling and promotes antiapoptotic/cell survival via ERK-nuclear factor erythroid-derived 2-like 2/antioxidative protein expression. N-cadherin was identified as a novel CTRP9 receptor mediating ADSCs signaling. Blockade of either N-cadherin or ERK1/2 completely abolished the previously noted CTRP9 effects. Although CTRP9 failed to promote ADSCs cardiogenic differentiation, CTRP9 promotes superoxide dismutase 3 expression and secretion from ADSCs, protecting cardiomyocytes against oxidative stress-induced cell death.
Conclusions
We provide the first evidence that CTRP9 promotes ADSCs proliferation/survival, stimulates ADSCs migration, and attenuates cardiomyocyte cell death by previously unrecognized signaling mechanisms. These include binding with N-cadherin, activation of ERK-matrix metallopeptidase 9 and ERK-nuclear factor erythroid-derived 2-like 2 signaling, and upregulation/secretion of antioxidative proteins. These results suggest that CTRP9 is a cardiokine critical in maintaining a healthy microenvironment facilitating stem cell engraftment in infarcted myocardial tissue, thereby enhancing stem cell therapeutic efficacy.
Open Access
Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix.
(Tissue Eng Part A, 2010-02) Diekman, Brian O; Rowland, Christopher R; Lennon, Donald P; Caplan, Arnold I; Guilak, Farshid
OBJECTIVES: Adipose-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (MSCs) are multipotent adult stem cells with potential for use in cartilage tissue engineering. We hypothesized that these cells show distinct responses to different chondrogenic culture conditions and extracellular matrices, illustrating important differences between cell types. METHODS: Human ASCs and MSCs were chondrogenically differentiated in alginate beads or a novel scaffold of reconstituted native cartilage-derived matrix with a range of growth factors, including dexamethasone, transforming growth factor beta3, and bone morphogenetic protein 6. Constructs were analyzed for gene expression and matrix synthesis. RESULTS: Chondrogenic growth factors induced a chondrocytic phenotype in both ASCs and MSCs in alginate beads or cartilage-derived matrix. MSCs demonstrated enhanced type II collagen gene expression and matrix synthesis as well as a greater propensity for the hypertrophic chondrocyte phenotype. ASCs had higher upregulation of aggrecan gene expression in response to bone morphogenetic protein 6 (857-fold), while MSCs responded more favorably to transforming growth factor beta3 (573-fold increase). CONCLUSIONS: ASCs and MSCs are distinct cell types as illustrated by their unique responses to growth factor-based chondrogenic induction. This chondrogenic induction is affected by the composition of the scaffold and the presence of serum.
Open Access
Diet-induced obesity alters the differentiation potential of stem cells isolated from bone marrow, adipose tissue and infrapatellar fat pad: the effects of free fatty acids.
(Int J Obes (Lond), 2013-08) Wu, C-L; Diekman, BO; Jain, D; Guilak, F
INTRODUCTION: Obesity is a major risk factor for several musculoskeletal conditions that are characterized by an imbalance of tissue remodeling. Adult stem cells are closely associated with the remodeling and potential repair of several mesodermally derived tissues such as fat, bone and cartilage. We hypothesized that obesity would alter the frequency, proliferation, multipotency and immunophenotype of adult stem cells from a variety of tissues. MATERIALS AND METHODS: Bone marrow-derived mesenchymal stem cells (MSCs), subcutaneous adipose-derived stem cells (sqASCs) and infrapatellar fat pad-derived stem cells (IFP cells) were isolated from lean and high-fat diet-induced obese mice, and their cellular properties were examined. To test the hypothesis that changes in stem cell properties were due to the increased systemic levels of free fatty acids (FFAs), we further investigated the effects of FFAs on lean stem cells in vitro. RESULTS: Obese mice showed a trend toward increased prevalence of MSCs and sqASCs in the stromal tissues. While no significant differences in cell proliferation were observed in vitro, the differentiation potential of all types of stem cells was altered by obesity. MSCs from obese mice demonstrated decreased adipogenic, osteogenic and chondrogenic potential. Obese sqASCs and IFP cells showed increased adipogenic and osteogenic differentiation, but decreased chondrogenic ability. Obese MSCs also showed decreased CD105 and increased platelet-derived growth factor receptor α expression, consistent with decreased chondrogenic potential. FFA treatment of lean stem cells significantly altered their multipotency but did not completely recapitulate the properties of obese stem cells. CONCLUSIONS: These findings support the hypothesis that obesity alters the properties of adult stem cells in a manner that depends on the cell source. These effects may be regulated in part by increased levels of FFAs, but may involve other obesity-associated cytokines. These findings contribute to our understanding of mesenchymal tissue remodeling with obesity, as well as the development of autologous stem cell therapies for obese patients.
Open Access
Fatty infiltration of the cervical extensor musculature, cervical sagittal balance, and clinical outcomes: An analysis of operative adult cervical deformity patients.
(Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2020-02) Passias, Peter G; Segreto, Frank A; Horn, Samantha R; Lafage, Virginie; Lafage, Renaud; Smith, Justin S; Naessig, Sara; Bortz, Cole; Klineberg, Eric O; Diebo, Bassel G; Sciubba, Daniel M; Neuman, Brian J; Hamilton, D Kojo; Burton, Douglas C; Hart, Robert A; Schwab, Frank J; Bess, Shay; Shaffrey, Christopher I; Nunley, Pierce; Ames, Christopher P; International Spine Study Group
PURPOSE:To assess preliminary associations between fatty-infiltration (FI) of cervical spine extensor musculature, cervical sagittal balance, and clinical outcomes in cervical deformity (CD) patients. METHODS:Operative CD patients (C2-C7 Cobb > 10°, CL > 10°, cSVA > 4 cm, or CBVA > 25°) with pre-operative (BL) MRIs and 1-year (1Y) post-operative MRIs or CTs were assessed for fatty-infiltration of cervical extensor musculature, using dedicated imaging software at each C2-C7 intervertebral level and the apex of deformity (apex). FI was gauged as a ratio of fat-free-muscle-cross-sectional-area (FCSA) over total-muscle-CSA (TCSA), with lower ratio values indicating greater FI. BL-1Y associations between FI, sagittal alignment, and clinical outcomes were assessed using appropriate parametric and non-parametric tests. RESULTS:22 patients were included (Age 59.22, 71.4%F, BMI 29.2, CCI:0.75, Frailty: 0.43). BL deformity presentation: TS-CL: 29.0°, C2-C7 Sagittal Cobb:-1.6°, cSVA:30.4 mm. No correlations were observed between BL fatty-infiltration, sagittal alignment, frailty, or clinical outcomes (p > 0.05). Following surgical correction, C2-C7 (BL: 0.59 vs 1Y:0.67, p = 0.005) and apex (BL: 0.59 vs. 1Y: 0.66, p = 0.33) fatty-infiltration decreased. Achievement of lordotic curvature correlated with C2-C7 fatty infiltration reduction (Rs: 0.495, p < 0.05), and patients with residual postoperative TS-CL and cSVA malalignment were associated with greater apex fatty-infiltration (Rs: -0.565, -0.561; p < 0.05). C2-C7 FI improvement was associated with NRS back pain reduction (Rs: -0.630, p < 0.05), and greater apex fatty-infiltration at BL was associated with minor perioperative complication occurrence (Rs: 0.551, p = 0.014). CONCLUSIONS:Deformity correction and sagittal balance appear to influence the reestablishment of cervical muscle tone from C2-C7 and reduction of back pain for severely frail CD patients. This analysis helps to understand cervical extensor musculature's role amongst CD patients.
Open Access
Interstitial engraftment of adipose-derived stem cells into an acellular dermal matrix results in improved inward angiogenesis and tissue incorporation.
(J Biomed Mater Res A, 2013-10) Komatsu, Issei; Yang, Jun; Zhang, Ying; Levin, L Scott; Erdmann, D; Klitzman, Bruce; Hollenbeck, Scott T
Acellular dermal matrices (ADM) are commonly used in reconstructive procedures and rely on host cell invasion to become incorporated into host tissues. We investigated different approaches to adipose-derived stem cells (ASCs) engraftment into ADM to enhance this process. Lewis rat adipose-derived stem cells were isolated and grafted (3.0 × 10(5) cells) to porcine ADM disks (1.5 mm thick × 6 mm diameter) using either passive onlay or interstitial injection seeding techniques. Following incubation, seeding efficiency and seeded cell viability were measured in vitro. In addition, Eighteen Lewis rats underwent subcutaneous placement of ADM disk either as control or seeded with PKH67 labeled ASCs. ADM disks were seeded with ASCs using either onlay or injection techniques. On day 7 and or 14, ADM disks were harvested and analyzed for host cell infiltration. Onlay and injection techniques resulted in unique seeding patterns; however cell seeding efficiency and cell viability were similar. In-vivo studies showed significantly increased host cell infiltration towards the ASCs foci following injection seeding in comparison to control group (p < 0.05). Moreover, regional endothelial cell invasion was significantly greater in ASCs injected grafts in comparison to onlay seeding (p < 0.05). ADM can successfully be engrafted with ASCs. Interstitial engraftment of ASCs into ADM via injection enhances regional infiltration of host cells and angiogenesis, whereas onlay seeding showed relatively broad and superficial cell infiltration. These findings may be applied to improve the incorporation of avascular engineered constructs.
Open Access
Ligament-derived matrix stimulates a ligamentous phenotype in human adipose-derived stem cells.
(Tissue Eng Part A, 2010-07) Little, Dianne; Guilak, Farshid; Ruch, David S
Human adipose stem cells (hASCs) can differentiate into a variety of phenotypes. Native extracellular matrix (e.g., demineralized bone matrix or small intestinal submucosa) can influence the growth and differentiation of stem cells. The hypothesis of this study was that a novel ligament-derived matrix (LDM) would enhance expression of a ligamentous phenotype in hASCs compared to collagen gel alone. LDM prepared using phosphate-buffered saline or 0.1% peracetic acid was mixed with collagen gel (COL) and was evaluated for its ability to induce proliferation, differentiation, and extracellular matrix synthesis in hASCs over 28 days in culture at different seeding densities (0, 0.25 x 10(6), 1 x 10(6), or 2 x 10(6) hASC/mL). Biochemical and gene expression data were analyzed using analysis of variance. Fisher's least significant difference test was used to determine differences between treatments following analysis of variance. hASCs in either LDM or COL demonstrated changes in gene expression consistent with ligament development. hASCs cultured with LDM demonstrated more dsDNA content, sulfated-glycosaminoglycan accumulation, and type I and III collagen synthesis, and released more sulfated-glycosaminoglycan and collagen into the medium compared to hASCs in COL (p
Open Access
Macrophage and adipocyte interaction as a source of inflammation in kidney disease.
(Scientific reports, 2021-02-03) Martos-Rus, Cristina; Katz-Greenberg, Goni; Lin, Zhao; Serrano, Eurico; Whitaker-Menezes, Diana; Domingo-Vidal, Marina; Roche, Megan; Ramaswamy, Kavitha; Hooper, Douglas C; Falkner, Bonita; Martinez Cantarin, Maria P
In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose tissue of end stage renal disease subjects revealed increased macrophage infiltration compared to controls after BMI stratification. Similarly, mice with kidney disease recapitulated the inflammatory state observed in uremic patients and additionally demonstrated increased peripheral monocytes and inflammatory polarization of adipose tissue macrophages (ATMS). In contrast, adipose tissue in uremic IL-6 knock out mice showed reduced ATMS density compared to uremic wild-type controls. Differences in ATMS density highlight the necessary role of IL-6 in macrophage infiltration in uremia. Uremia promotes changes in adipocytes and macrophages enhancing production of inflammatory cytokines. We demonstrate an interaction between uremic activated macrophages and adipose tissue that augments inflammation in uremia.
Open Access
Of fruits and fats: high-sugar diets restore fatty acid profiles in the white adipose tissue of captive dwarf lemurs.
(Proceedings. Biological sciences, 2022-06) Blanco, MB; Greene, LK; Ellsaesser, LN; Schopler, B; Davison, M; Ostrowski, C; Klopfer, PH; Fietz, J; Ehmke, EE
Fat-storing hibernators rely on fatty acids from white adipose tissue (WAT) as an energy source to sustain hibernation. Whereas arctic and temperate hibernators preferentially recruit dietary polyunsaturated fatty acids (PUFAs), tropical hibernators can rely on monounsaturated fatty acids that produce fewer lipid peroxides during oxidation. Nevertheless, compositional data on WAT from tropical hibernators are scant and questions remain regarding fat recruitment and metabolism under different environmental conditions. We analyse fatty acid profiles from the WAT of captive dwarf lemurs (Cheirogaleus medius) subjected to high-sugar or high-fat diets during fattening and cold or warm conditions during hibernation. Dwarf lemurs fed high-sugar (compared to high-fat) diets displayed WAT profiles more comparable to wild lemurs that fatten on fruits and better depleted their fat reserves during hibernation. One PUFA, linoleic acid, remained elevated before hibernation, potentially lingering from the diets provisioned prior to fattening. That dwarf lemurs preferentially recruit the PUFA linoleic acid from diets that are naturally low in availability could explain the discrepancy between captive and wild lemurs' WAT. While demonstrating that minor dietary changes can produce major changes in seasonal fat deposition and depletion, our results highlight the complex role for PUFA metabolism in the ecology of tropical hibernators.
Open Access
T cell-depleted cultured pediatric thymus tissue as a model for some aspects of human age-related thymus involution.
(GeroScience, 2021-06) Hale, Laura P; Cheatham, Lynn; Macintyre, Andrew N; LaFleur, Bonnie; Sanders, Brittany; Troy, Jesse; Kurtzberg, Joanne; Sempowski, Gregory D
Human age-related thymus involution is characterized by loss of developing thymocytes and the thymic epithelial network that supports them, with replacement by adipose tissue. The mechanisms that drive these changes are difficult to study in vivo due to constant trafficking to and from the thymus. We hypothesized that the loss of thymocytes that occurs during human thymic organ cultures could model some aspects of thymus involution and begin to identify mechanisms that drive age-related changes in the thymic microenvironment. Potential mechanistically important candidate molecules were initially identified by screening conditioned media from human thymus organ cultures using antibody microarrays. These candidates were further validated using cultured tissue extracts and conditioned media. Results were compared with gene expression studies from a panel of well-characterized (non-cultured) human thymus tissues from human donors aged 5 days to 78 years. L-selectin released into conditioned media was identified as a biomarker for the content of viable thymocytes within the cultured thymus. Levels of the chemokines CCL21 and CXCL12, likely produced by surviving thymic epithelial cells, increased markedly in conditioned media as thymocytes were lost during culture. Native non-cultured thymus from adults older than 18 years also showed a strong trend toward increased CCL21 expression, in conjunction with significant decreases in thymocyte-related mRNAs compared with thymus from subjects younger than 18 years. Together, these findings demonstrate that use of postnatal human thymus organ cultures can model some aspects of human age-related thymic involution.
Open Access
Tissue engraftment of hypoxic-preconditioned adipose-derived stem cells improves flap viability.
(Wound Repair Regen, 2012-11) Hollenbeck, Scott T; Senghaas, Annika; Komatsu, Issei; Zhang, Ying; Erdmann, Detlev; Klitzman, Bruce
Adipose-derived stem cells (ASCs) have the ability to release multiple growth factors in response to hypoxia. In this study, we investigated the potential of ASCs to prevent tissue ischemia. We found conditioned media from hypoxic ASCs had increased levels of vascular endothelial growth factor (VEGF) and enhanced endothelial cell tubule formation. To investigate the effect of injecting rat ASCs into ischemic flaps, 21 Lewis rats were divided into three groups: control, normal oxygen ASCs (10(6) cells), and hypoxic preconditioned ASCs (10(6) cells). At the time of flap elevation, the distal third of the flap was injected with the treatment group. At 7 days post flap elevation, flap viability was significantly improved with injection of hypoxic preconditioned ASCs. Cluster of differentiation-31-positive cells were more abundant along the margins of flaps injected with ASCs. Fluorescent labeled ASCs localized aside blood vessels or throughout the tissue, dependent on oxygen preconditioning status. Next, we evaluated the effect of hypoxic preconditioning on ASC migration and chemotaxis. Hypoxia did not affect ASC migration on scratch assay or chemotaxis to collagen and laminin. Thus, hypoxic preconditioning of injected ASCs improves flap viability likely through the effects of VEGF release. These effects are modest and represent the limitations of cellular and growth factor-induced angiogenesis in the acute setting of ischemia.

Browsing by Subject "Adipose Tissue"

Background

Methods

Results

Conclusions