Modulating SPARC Expression in Mesenchymal Stem Cells Improves Secretome-Mediated Skin Regeneration and Wound Repair
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PROVIDER: PRJNA1284783 | ENA |
REPOSITORIES: ENA
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Project description:Mesenchymal stem cells (MSCs) have garnered significant attention over the past three decades due to their robust regenerative potential, primarily mediated by their paracrine activity by releasing soluble bioactive factors and extracellular vesicles (EVs). The MSC secretome plays a pivotal role in wound healing by influencing cellular migration, inflammation, angiogenesis, extracellular matrix (ECM) remodeling, and re-epithelialization. SPARC (Secreted Protein Acidic and Rich in Cysteine), a multifunctional ECM glycoprotein involved in tissue repair and remodeling, regulates key processes such as cell migration, proliferation, angiogenesis, and survival. Despite its known role in ECM dynamics, the impact of SPARC expression on the regenerative properties of MSCs remains underexplored. In this study, we hypothesized that SPARC overexpression in MSCs enhances their secretome's regenerative capacity. Using lentiviral systems, we generated SPARCoverexpressing (+SPARC) and SPARC-knockdown (KD-SPARC) MSCs to investigate SPARC's role in wound healing. Conditioned media (CM) derived from these MSCs were analyzed in vitro for their effects on human skin keratinocytes and fibroblasts. Our results revealed that SPARC expression significantly influences cell-specific migration and cell cycle. Furthermore, in an in vivo wound healing model, CM from +SPARC MSCs accelerated regeneration, while SPARC absence in MSCs CM delayed the healing process. These findings underscore the critical role of SPARC in modulating MSC secretome composition and enhancing its regenerative efficacy. This study highlights SPARC as a promising therapeutic target for the development of advanced regenerative therapies aimed at improving cutaneous wound healing outcomes
2025-07-15 | GSE301307 | GEO
Project description:Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem-cell secretome product which contains a host of growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of bi-weekly unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57Bl/6 mice (22-23 months) compared to saline injected aged-matched controls. After 4 weeks of treatment, secretome delivery substantially increased whole body lean mass and decreased fat mass corresponding to higher fiber cross sectional area and smaller adipocyte size, respectively. Secretome-treated mice also displayed improved whole-body grip strength and rotarod performance and had higher energy expenditure and physical activity levels compared to control mice. Furthermore, secretome-treated mice had greater skeletal muscle Pax7+ cell abundance, capillary density, and collagen turnover. Finally, the secretome product reduced lipid content and lipid droplet size in adipocytes in vitro. These data suggest intramuscular treatment secretome improves whole-body metabolism, physical function, and remodels skeletal muscle and adipose tissue in aged mice.
2024-07-31 | GSE242211 | GEO
Project description:Venous leg ulcers (VLU) represent a clinical challenge and impair the patient’s quality of life. Venous insufficiency is underlying the protracted healing. We report the protein expression pattern for biomarkers in VLU wound fluids and compare these with acute split-thickness wound fluids.
Fifty-seven patients with VLU were recruited and treated for 12 weeks with a protease-modulating polyacrylate wound dressing and a two-layer bandage compression system. Ten patients with acute wounds were followed for 21 days. Wound size decreased from 18.7 ± 12.3 cm2 to 11.75 ± 11.39 cm2 in the VLU cohort, 10 wounds healed completely. Relative wound area reduction reached 48.9% ± 51.9% at week 12. 61.4% of the patients achieved a relative wound area reduction of ≥40% and 50.9% a relative wound area reduction of ≥60%.
IL-1beta, TNF-alpha, and MMP9 concentration ranges were similar in VLU and acute wound fluids. Concentrations of S100A8, S100A9, neutrophil elastase, MMP2, and fibronectin were elevated in VLU wound fluids and decreased significantly in abundance after two weeks of treatment. The values remained low, yet, higher than those of acute wounds. Collagen (I) alpha1 abundance was higher in VLU wound fluids and not significantly regulated.
Our data show a robust healing response in venous leg ulcers treated with a protease-modulating polyacrylate wound dressing. The biomarker pattern in VLU wound fluids changed within the first two weeks and we speculate that this might reflect a decrease of STAT3 influence in the wound bed.
2023-08-22 | PXD025748 | panorama
Project description:MicroRNAs (miRNAs) are small noncoding RNAs that critically regulate gene expression. Their abundance and function have been linked to processes such as senescence and aging. In aged monkey muscle, miR-451a and miR-144-3p were highly upregulated compared to young animals. This led us to hypothesize that the miRNAs 451a/144-3p may be involved in muscle differentiation. We found that these miRNAs are downregulated during the differentiation of C2C12 myoblasts. Overexpression of miR-451a, but not miR-144-3p, robustly impeded the differentiation, suggesting an inhibitory role for miR-451a. We further investigated the potential regulatory targets of miR-451a and identified Sparc mRNA, encoding a secreted protein acidic and rich in cysteine (SPARC), which is involved in wound healing and cellular differentiation. Interestingly, we found that miR-451a suppresses Sparc mRNA translation according to the analysis of polysome profile. Our findings show that miR-451a is downregulated in differentiated myoblasts and decreases C2C12 differentiation at least in part by the suppression of SPARC biosynthesis.
2019-04-03 | GSE119186 | GEO
Project description:The aim of this study was evaluate the transcriptome changes in the comparison between triple negative tumors with increased SPARC expression and triple negative tumors with decreased SPARC expression according to Nagai et al., 2011 (Breast Cancer Res Treat (2011) 126:1–14) The results generated could be of particular interest to better define the prognostic impact of SPARC expression in triple negative breast tumors
2018-07-01 | GSE98931 | GEO
Project description:Severe angiopathy has been postulated as a major driver for diabetes associated secondary complications. So far the knowledge on underlying mechanisms and thereon based therapeutic options to attenuate these pathologies are limited. Here we systematically administered ABCB5+ MSCs for the treatment of chronic non-healing diabetic wounds employing db/db mice, a type II diabetes model as their number markedly declined during diabetes. We found that administration of ABCB5+ MSCs markedly accelerates wound closure in diabetic db/db mice as opposed to the vehicle treated control group. Strikingly, administration of ABCB5+ MSCs at the edges of the diabetic wounds triggered considerable neoangiogenesis, most likely by the releasing a Ribonuclease angiogenin that was identified through secretome analysis of ABCB5+ MSCs. Interestingly, silencing of angiogenin in ABCB5+ MSCs significantly delayed wound closure in diabetic db/db mice indicating its key role in skin regeneration. Moreover, angiogenin also impacted the polarization of macrophages. The findings from this study will provide novel insight into the unique capacity of ABCB5+ MSCs to mount an adaptive response at the wound site with the delivery of angiogenic molecules holds significant promise for the therapy of non-healing diabetes foot ulcers, and other pathologies with impaired angiogenesis. The benefits for refined stem cell based therapies is virtually unlimited.
2020-01-24 | GSE144169 | GEO
Project description:SPARC is a matricellular glycoprotein involved in regulation of the extracellular matrix, growth factors, adhesion, and migration. SPARC-null mice have altered basement membranes and develop posterior sub-capsular cataracts with cell swelling and equatorial vacuoles. Exchange of fluid, nutrients, and waste products in the avascular lens is driven by a unique circulating ion current. Here we demonstrate that SPARC-null mouse lenses exhibit abnormal circulation of fluid, ion, and small molecules which leads to altered fluorescein distribution in vivo, loss of resting membrane polarization, and altered distribution of small molecules. Microarray analysis of SPARC-null lenses showed changes in gene expression of ion channels and receptors, matrix and adhesion genes, cytoskeleton, immune response genes, and cell signaling molecules. Our results demonstrate that the regulation of SPARC on cell-capsular matrix interactions can influence the circulation of fluid and ions in the lens, and the phenotype in the SPARC-null mouse lens is the result of multiple intersecting pathways.
2009-05-01 | GSE13402 | GEO
Project description:SPARC is a matricellular glycoprotein involved in regulation of the extracellular matrix, growth factors, adhesion, and migration. SPARC-null mice have altered basement membranes and develop posterior sub-capsular cataracts with cell swelling and equatorial vacuoles. Exchange of fluid, nutrients, and waste products in the avascular lens is driven by a unique circulating ion current. Here we demonstrate that SPARC-null mouse lenses exhibit abnormal circulation of fluid, ion, and small molecules which leads to altered fluorescein distribution in vivo, loss of resting membrane polarization, and altered distribution of small molecules. Microarray analysis of SPARC-null lenses showed changes in gene expression of ion channels and receptors, matrix and adhesion genes, cytoskeleton, immune response genes, and cell signaling molecules. Our results demonstrate that the regulation of SPARC on cell-capsular matrix interactions can influence the circulation of fluid and ions in the lens, and the phenotype in the SPARC-null mouse lens is the result of multiple intersecting pathways. Experiment Overall Design: Lens epithelial cells from 7 lenses of littermate mice were isolated by laser capture microdissection. 3 wild-type lenses from 3 different mice and 4 knock-out lenses from 3 different mice were used as biological replicates.
2009-05-11 | E-GEOD-13402 | biostudies-arrayexpress
Project description:Metabolic dysfunction of skeletal muscle is often prevalent at an early stage in the development of several non-communicable diseases. Here, we investigated the effect of a myokine, secreted protein acidic and rich in cysteine (SPARC), on glucose tolerance in human and mouse skeletal muscles. SPARC knockout mice showed marked decreases in parameters for whole-body glucose metabolism, along with reduced phosphorylation of AMPK and Akt in skeletal muscle tissues compared with wild-type mice. Furthermore, mice injected with SPARC showed improved glucose tolerance concomitant with AMPK activation. Exogenous SPARC treatment accelerated glucose uptake in muscle tissues isolated from wild-type mice but not from AMPKγ3 knockout mice. In muscle cells, SPARC increased glucose uptake concomitant with AMPK activation, mediated by a calcium-dependent signal. Chronic treatment of SPARC restored metabolic functions in diet-induced obese mice. These findings suggest that SPARC improves glucose metabolism via AMPK activation in skeletal muscle, providing mechanistic insights on exercise-induced metabolic benefits and physical inactivity-induced glucose intolerance.
2019-06-03 | GSE93546 | GEO