Papers by Abdullah Aldahmash
Journal of Applied Hematology, Oct 1, 2011
Current neurobiology, 2011
This study aimed to characterize ganglion hypertrophy in the major pelvic ganglion (MPG) of male ... more This study aimed to characterize ganglion hypertrophy in the major pelvic ganglion (MPG) of male rats after contralateral ganglionectomy. Eighteen adult male Sprague-Dawley rats were used in this study. Nine of them were subjected to long-term (6 weeks) contralateral ...
Scientific Reports, Jul 3, 2023
Stem Cells International, 2018
Bone marrow mesenchymal stem cells (BMSCs) are adult multipotent stem cells that can differentiat... more Bone marrow mesenchymal stem cells (BMSCs) are adult multipotent stem cells that can differentiate into mesodermal lineage cells, including adipocytes and osteoblasts. However, the epigenetic mechanisms governing the lineage-specific commitment of BMSCs into adipocytes or osteoblasts are under investigation. Herein, we investigated the epigenetic effect of romidepsin, a small molecule dual inhibitor targeting HDAC1 and HDAC2 identified through an epigenetic library functional screen. BMSCs exposed to romidepsin (5 nM) exhibited enhanced adipocytic and osteoblastic differentiation. Global gene expression and signaling pathway analyses of differentially expressed genes revealed a strong enrichment of genes involved in adipogenesis and osteogenesis in romidepsin-treated BMSCs during induction into adipocytes or osteoblasts, respectively. Pharmacological inhibition of FAK signaling during adipogenesis or inhibition of FAK or TGFβ signaling during osteogenesis diminished the biological effects of romidepsin on BMSCs. The results of chromatin immunoprecipitation combined with quantitative polymerase chain reaction indicated a significant increase in H3K9Ac epigenetic markers in the promoter regions of peroxisome proliferator-activated receptor gamma (PPARγ) and KLF15 (related to adipogenesis) or SP7 (Osterix) and alkaline phosphatase (ALP) (related to osteogenesis) in romidepsin-treated BMSCs. Our data indicated that romidepsin is a novel in vitro modulator of adipocytic and osteoblastic differentiation of BMSCs.
Scientific Reports, Mar 21, 2019
targeting regulatory signaling pathways that control human bone marrow stromal (skeletal or mesen... more targeting regulatory signaling pathways that control human bone marrow stromal (skeletal or mesenchymal) stem cell (hBMSC) differentiation and lineage fate determination is gaining momentum in the regenerative medicine field. Therefore, to identify the central regulatory mechanism of osteoblast differentiation of hBMSCs, the molecular phenotypes of two clonal hBMSC lines exhibiting opposite in vivo phenotypes, namely, bone forming (hBMsC +bone) and non-bone forming (hBMsC −Bone) cells, were studied. Global transcriptome analysis revealed significant downregulation of several tGFβ responsive genes, namely, TAGLN, TMP1, ACTA2, TGFβ2, SMAD6, SMAD9, BMP2, and BMP4 in hBMsC −Bone cells and upregulation on SERPINB2 and NOG. Transcriptomic data was associated with marked reduction in SMAD2 protein phosphorylation, which thereby implies the inactivation of TGFβ and BMp signaling in those cells. Concordantly, activation of tGFβ signaling in hBMsC −Bone cells using either recombinant tGFβ1 protein or knockdown of SERPINB2 TGFβ-responsive gene partially restored their osteoblastic differentiation potential. Similarly, the activation of BMP signaling using exogenous BMP4 or via siRNA-mediated knockdown of NOG partially restored the differentiation phenotype of hBMsC −Bone cells. Concordantly, recombinant NoG impaired ex vivo osteoblastic differentiation of hBMsC +Bone cells, which was associated with SERBINB2 upregulation. Our data suggests the existence of reciprocal relationship between tGFB and BMp signaling that regulates hBMsC lineage commitment and differentiation, whilst provide a plausible strategy for generating osteoblastic committed cells from hBMsCs for clinical applications. Human bone marrow-derived stromal (skeletal or mesenchymal) stem cells (hBMSC) exhibit the potential to differentiate into various mesodermal cells including osteoblasts, adipocytes, and chondrocytes 1. These have all been employed in regenerative medicine protocols for treating skeletal diseases e.g. non-healed fractures and the repair of bone defects 2. However, cultured hBMSC cells exhibit functional and molecular heterogeneity with respect to differentiation capacity and bone formation potential 3,4. This may explain the variability in the results obtained from hBMSC-based therapies 5. One possible approach to enhance the therapeutic efficacy of hBMSC in bone regeneration protocols is to employ osteoblast-committed progenitors. Moreover, in certain disease conditions such as osteoporosis, for example, the impairment of osteoblast differentiation of hBMSC occurs, thereby necessitating the in vivo enhancement of the bone forming capacity of hBMSC 6. However, this requires the identification of the signaling pathways and molecules that regulate hBMSC commitment into the osteoblastic lineage 7,8. We have previously employed global transcriptomics and proteomic approaches in order to identify the molecules and signaling pathways regulating hBMSC lineage specific differentiation based on studying the in vitro differentiation dynamics of hBMSC 3,9-11. Several follow up studies led to the identification of factors that are relevant for in vitro osteoblast differentiation and in vivo bone formation 12,13. Whilst this approach is both useful
Stem Cell Research, Apr 1, 2017
Understanding the regulatory networks underlying lineage differentiation and fate determination o... more Understanding the regulatory networks underlying lineage differentiation and fate determination of human bone marrow stromal cells (hBMSC) is a prerequisite for their therapeutic use. The goal of the current study was to unravel the novel role of the low-density lipoprotein receptor-related protein 3 (LRP3) in regulating the osteogenic and adipogenic differentiation of immortalized hBMSCs. Gene expression profiling revealed significantly higher LRP3 levels in the highly osteogenic hBMSC clone imCL1 than in the less osteogenic clone imCL2, as well as a significant upregulation of LRP3 during the osteogenic induction of the imCL1 clone. Data from functional and gene expression assays demonstrated the role of LRP3 as a molecular switch promoting hBMSC lineage differentiation into osteoblasts and inhibiting differentiation into adipocytes. Interestingly, microRNA (miRNA) expression profiling identified miR-4739 as the most under-represented miRNA (−36.11 fold) in imCL1 compared to imCL2. The TargetScan prediction algorithm, combined with functional and biochemical assays, identified LRP3 mRNA as a novel target of miR-4739, with a single potential binding site for miR-4739 located in the LRP3 3′ UTR. Regulation of LRP3 expression by miR-4739 was subsequently confirmed by qRT-PCR, western blotting, and luciferase assays. Over-expression of miR-4739 mimicked the effects of LRP3 knockdown on promoting adipogenic and suppressing osteogenic differentiation of hBMSCs. Hence, we report for the first time a novel biological role for the LRP3/hsa-miR-4739 axis in balancing osteogenic and adipocytic differentiation of hBMSCs. Our data support the potential utilization of miRNA-based therapies in regenerative medicine.
Stem Cells International, Nov 21, 2019
Background. Hedgehog (Hh) signaling is essential for osteoblast differentiation of mesenchymal pr... more Background. Hedgehog (Hh) signaling is essential for osteoblast differentiation of mesenchymal progenitors during endochondral bone formation. However, the critical role of Hh signaling during adult bone remodeling remains to be elucidated. Methods. A Smoothened (SMO) antagonist/Hedgehog inhibitor, BMS-833923, identified during a functional screening of a stem cell signaling small molecule library, was investigated for its effects on the osteoblast differentiation of human skeletal (mesenchymal) stem cells (hMSC). Alkaline phosphatase (ALP) activity and Alizarin red staining were employed as markers for osteoblast differentiation and in vitro mineralization capacity, respectively. Global gene expression profiling was performed using the Agilent® microarray platform. Effects on in vivo ectopic bone formation were assessed by implanting hMSC mixed with hydroxyapatite-tricalcium phosphate granules subcutaneously in 8-week-old female nude mice, and the amount of bone formed was assessed using quantitative histology. Results. BMS-833923, a SMO antagonist/Hedgehog inhibitor, exhibited significant inhibitory effects on osteoblast differentiation of hMSCs reflected by decreased ALP activity, in vitro mineralization, and downregulation of osteoblast-related gene expression. Similarly, we observed decreased in vivo ectopic bone formation. Global gene expression profiling of BMS-833923-treated compared to vehicle-treated control cells, identified 348 upregulated and 540 downregulated genes with significant effects on multiple signaling pathways, including GPCR, endochondral ossification, RANK-RANKL, insulin, TNF alpha, IL6, and inflammatory response. Further bioinformatic analysis employing Ingenuity Pathway Analysis revealed significant enrichment in BMS-833923-treated cells for a number of functional categories and networks involved in connective and skeletal tissue development and disorders, e.g., NFκB and STAT signaling. Conclusions. We identified SMO/Hedgehog antagonist (BMS-833923) as a powerful inhibitor of osteoblastic differentiation of hMSC that may be useful as a therapeutic option for treating conditions associated with high heterotopic bone formation and mineralization.
Differentiation, Nov 1, 2018
, NR2F1 mediated down-regulation of osteoblast differentiation was rescued by Bone morphogenetic ... more , NR2F1 mediated down-regulation of osteoblast differentiation was rescued by Bone morphogenetic protein-2 (BMP-2) in human MSC, Differentiation,
Stem Cells Translational Medicine, May 18, 2016
The epigenetic mechanisms promoting lineage-specific commitment of human skeletal (mesenchymal or... more The epigenetic mechanisms promoting lineage-specific commitment of human skeletal (mesenchymal or stromal) stem cells (hMSCs) into adipocytes or osteoblasts are still not fully understood. Herein, we performed an epigenetic library functional screen and identified several novel compounds, including abexinostat, which promoted adipocytic and osteoblastic differentiation of hMSCs. Using gene expression microarrays, chromatin immunoprecipitation for H3K9Ac combined with highthroughput DNA sequencing (ChIP-seq), and bioinformatics, we identified several key genes involved in regulating stem cell proliferation and differentiation that were targeted by abexinostat. Concordantly, ChIP-quantitative polymerase chain reaction revealed marked increase in H3K9Ac epigenetic mark on the promoter region of AdipoQ, FABP4, PPARg, KLF15, CEBPA, SP7, and ALPL in abexinostattreated hMSCs. Pharmacological inhibition of focal adhesion kinase (PF-573228) or insulin-like growth factor-1R/insulin receptor (NVP-AEW51) signaling exhibited significant inhibition of abexinostatmediated adipocytic differentiation, whereas inhibition of WNT (XAV939) or transforming growth factor-b (SB505124) signaling abrogated abexinostat-mediated osteogenic differentiation of hMSCs. Our findings provide insight into the understanding of the relationship between the epigenetic effect of histone deacetylase inhibitors, transcription factors, and differentiation pathways governing adipocyte and osteoblast differentiation. Manipulating such pathways allows a novel use for epigenetic compounds in hMSC-based therapies and tissue engineering.
Oncotarget, Apr 22, 2016
Colorectal cancer (CRC) is the third most common cancer causing high mortality rates worldwide. D... more Colorectal cancer (CRC) is the third most common cancer causing high mortality rates worldwide. Delineating the molecular mechanisms leading to CRC development and progression, including the role of microRNAs (miRNAs), are currently being unravelled at a rapid rate. Here, we report frequent downregulation of the microRNA miR-320 family in primary CRC tissues and cell lines. Lentiviral-mediated re-expression of miR-320c (representative member of the miR-320 family) inhibited HCT116 CRC growth and migration in vitro, sensitized CRC cells to 5-Fluorouracil (5-FU), and inhibited tumor formation in SCID mice. Global gene expression analysis in CRC cells over-expressing miR-320c, combined with in silico prediction identified 84 clinicallyrelevant potential gene targets for miR-320 in CRC. Using a series of biochemical assays and functional validation, SOX4, FOXM1, and FOXQ1 were validated as novel gene targets for the miR-320 family. Inverse correlation between the expression of miR-320 members with SOX4, FOXM1, and FOXQ1 was observed in primary CRC patients' specimens, suggesting that these genes are likely bona fide targets for the miR-320 family. Interestingly, interrogation of the expression levels of this gene panel (SOX4, FOXM1, and FOXQ1) in The Cancer Genome Atlas (TCGA) colorectal cancer data set (319 patients) revealed significantly poor disease-free survival in patients with elevated expression of this gene panel (P-Value: 0.0058). Collectively, our data revealed a novel role for the miR-320/SOX4/FOXM1/FOXQ1 axes in promoting CRC development and progression and suggest targeting those networks as potential therapeutic strategy for CRC.
Cell Death and Disease, Aug 4, 2016
Regenerative medicine is a novel approach for treating conditions in which enhanced bone regenera... more Regenerative medicine is a novel approach for treating conditions in which enhanced bone regeneration is required. We identified transgelin (TAGLN), a transforming growth factor beta (TGFβ)-inducible gene, as an upregulated gene during in vitro osteoblastic and adipocytic differentiation of human bone marrow-derived stromal (skeletal) stem cells (hMSC). siRNA-mediated gene silencing of TAGLN impaired lineage differentiation into osteoblasts and adipocytes but enhanced cell proliferation. Additional functional studies revealed that TAGLN deficiency impaired hMSC cell motility and in vitro transwell cell migration. On the other hand, TAGLN overexpression reduced hMSC cell proliferation, but enhanced cell migration, osteoblastic and adipocytic differentiation, and in vivo bone formation. In addition, deficiency or overexpression of TAGLN in hMSC was associated with significant changes in cellular and nuclear morphology and cytoplasmic organelle composition as demonstrated by high content imaging and transmission electron microscopy that revealed pronounced alterations in the distribution of the actin filament and changes in cytoskeletal organization. Molecular signature of TAGLN-deficient hMSC showed that several genes and genetic pathways associated with cell differentiation, including regulation of actin cytoskeleton and focal adhesion pathways, were downregulated. Our data demonstrate that TAGLN has a role in generating committed progenitor cells from undifferentiated hMSC by regulating cytoskeleton organization. Targeting TAGLN is a plausible approach to enrich for committed hMSC cells needed for regenerative medicine application.
Experimental Cell Research, Apr 1, 2011
The mechanisms underlying the inverse relationship between osteogenic and adipogenic differentiat... more The mechanisms underlying the inverse relationship between osteogenic and adipogenic differentiation of bone marrow stromal cells (MSC) are not known in detail. We have previously established two cell lines from mouse bone marrow that are committed to either osteogenic (osteoblasts and chondrocytes) (mMSC(Bone)) or adipogenic (mMSC(Adipo)) lineage. To identify the molecular mechanism determining the lineage commitment, we compared the basal gene expression profile of mMSC(Bone) versus mMSC(Adipo) using Affymetrix GeneChip® MG430A 2.0 Array. Gene annotation analysis based on biological function revealed an over-representation of skeletal development genes in mMSC(Bone) while genes related to lipid metabolism and immune response were highly expressed in mMSC(Adipo). In addition, there was a significant up-regulation of canonical Wnt signalling genes in mMSC(Bone) compared to mMSC(Adipo) (p<0.006). Dual-luciferase assay and expression analysis of genes related to Wnt signalling demonstrated significant activation of Wnt signalling pathway in mMSC(Bone) compared to mMSC(Adipo). Reduced Wnt activity in mMSC(Adipo) was associated with increased expression of the Wnt inhibitor, secreted frizzled-related protein 1 (sFRP-1) at both mRNA and protein levels in mMSC(Adipo). Interestingly, conditioned medium (CM) collected from mMSC(Adipo) (mMSC-CM(Adipo)) inhibited osteoblast differentiation of mMSC, while depletion of sFRP-1 protein from mMSC-CM(Adipo) abolished its inhibitory effect on osteoblast differentiation. Furthermore, treatment of mMSC with recombinant sFRP-1 resulted in a dose-dependent inhibition of osteoblast and stimulation of adipocyte differentiation. In conclusion, cross-talk exists between different populations of MSC in the bone marrow, and Wnt signalling functions as a molecular switch that determines the balance between osteoblastogenesis and adipogenesis.
Saudi Journal of Gastroenterology, 2017
Background/Aims: 5-Fluorouracil (5-FU) is widely used in the treatment of patients with colorecta... more Background/Aims: 5-Fluorouracil (5-FU) is widely used in the treatment of patients with colorectal cancer (CRC). However, the efficacy of 5-FU as a single agent is limited, with multiple undesired side effects. Therefore, the aim of the current study was to assess the efficacy of CUDC-907 (a dual inhibitor of histone deacetylase and phosphatidylinositide 3-kinase) in combination with 5-FU against CRC cells. Materials and Methods: Cell viability was determined using AlamarBlue and colony formation assays. Acridine orange/ethidium bromide staining and flow cytometry were used to measure apoptotic and necrotic events, as well as cell cycle progression. Immunoblotting was used to assess acetylation of histone H3 and phosphorylation of AKT. Results: Our data revealed enhanced toxicity of CUDC-907 against HCT116, RKO, COLO-205, and HT-29 CRC cells when combined with 5-FU. Similarly, the colony formation capability of HCT116 cells was suppressed by the combination treatment. Cells treated with CUDC-907 and 5-FU underwent apoptosis and necrosis, and exhibited increased polyploidy. Furthermore, CRC cells treated with CUDC-907 exhibited a higher degree of histone H3 lysine 9 acetylation (H3K9ac) and reduced AKT phosphorylation (Ser473). Conclusion: Our data revealed, for the first time, the enhanced inhibitory effect of CUDC-907 against CRC cells when combined with 5-FU, supporting the application of this combination as a potential therapeutic strategy in CRC treatment.
Oncotarget, Feb 5, 2018
Tumour heterogeneity leads to variable clinical response and inaccurate diagnostic and prognostic... more Tumour heterogeneity leads to variable clinical response and inaccurate diagnostic and prognostic assessment. Cancer stem cells (CSCs) represent a subpopulation responsible for invasion, metastasis, therapeutic resistance, and recurrence in many human cancer types. However, the true identity of colorectal cancer (CRC) SCs remains elusive. Here, we aimed to characterize and define the gene expression portrait of CSCs in CRC-model SW403 cells. We found that ALDH + positive cells are clonogenic and highly proliferative; their global gene expression profilingbased molecular signature revealed gene enrichment related to DNA damage, MAPK, FAK, oxidative stress response, and Wnt signalling. ALDH + cells showed enhanced ROS stress resistance, whereas MAPK/FAK pathway pharmacologic inhibition limited their survival. Conversely, 5-fluorouracil increased the ALDH + cell fraction among the SW403, HCT116 and SW620 CRC models. Notably, analysis of ALDH1A1 and POU5F1 expression levels in cohorts of 462 or 420 patients for overall (OS) or disease-free (DFS) survival, respectively, obtained from the Cancer Genome Atlas CRC dataset, revealed strong association between elevated expression and poor OS (p = 0.006) and poor DFS (p = 0.05), thus implicating ALDH1A1 and POU5F1 in CRC prognosis. Our data reveal distinct molecular signature of ALDH + CSCs in CRC and suggest pathways relevant for successful targeted therapies and management of CRC.
Bioscience Reports, Jan 30, 2018
Bone marrow adipocyte formation plays a role in bone homeostasis and whole body energy metabolism... more Bone marrow adipocyte formation plays a role in bone homeostasis and whole body energy metabolism. However, the transcriptional landscape and signaling pathways associated with adipocyte lineage commitment and maturation are not fully delineated. Thus, we performed global gene expression profiling during adipocyte differentiation of human bone marrow stromal (mesenchymal) stem cells (hMSCs) and identified 2,589 up-regulated and 2,583 down-regulated mRNA transcripts. Pathway analysis on the up-regulated gene list untraveled enrichment in multiple signaling pathways including insulin receptor signaling, focal Adhesion, metapathway biotransformation, a number of metabolic pathways e.g. selenium metabolism, Benzo(a)pyrene metabolism, fatty acid, triacylglycerol, ketone body metabolism, tryptophan metabolism, and catalytic cycle of mammalian flavin-containing monooxygenase (FMOs). On the other hand, pathway analysis on the down-regulated genes revealed significant enrichment in pathways related to cell cycle regulation. Based on these data, we assessed the effect of pharmacological inhibition of FAK signaling using PF-573228, PF-562271, and InsR/IGF-1R using NVP-AEW541 and GSK-1904529A on adipocyte differentiation. hMSCs exposed to FAK or IGF-1R/InsR inhibitors exhibited fewer adipocyte formation (27-58% inhibition, P<0005). Concordantly, the expression of adipocyte-specific genes AP2, AdipoQ, and CEBPα was significantly reduced. On the other hand, we did not detect significant effects on cell viability as a result of FAK or IGF-1R/InsR inhibition. Our data identified FAK and insulin signaling as important intracellular signaling pathways relevant to bone marrow adipogenesis.
Scientific Reports, May 16, 2016
Breast cancer (BC) is the most common cancer type and the second cause of cancer-related death am... more Breast cancer (BC) is the most common cancer type and the second cause of cancer-related death among women. Therefore, better understanding of breast cancer tumor biology and the identification of novel biomarkers is essential for the early diagnosis and for better disease stratification and management choices. Herein we developed a novel approach which relies on the isolation of circulating microRNAs through an enrichment step using speed-vacuum concentration which resulted in 5-fold increase in microRNA abundance. Global miRNA microarray expression profiling performed on individual samples from 23 BC and 9 normals identified 18 up-regulated miRNAs in BC patients (p(corr) < 0.05). Nine miRNAs (hsa-miR-4270, hsa-miR-1225-5p, hsa-miR-188-5p, hsa-miR-1202, hsa-miR-4281, hsa-miR-1207-5p, hsa-miR-642b-3p, hsa-miR-1290, and hsa-miR-3141) were subsequently validated using qRT-PCR in a cohort of 46 BC and 14 controls. The expression of those microRNAs was overall higher in patients with stage I, II, and III, compared to stage IV, with potential utilization for early detection. The expression of this microRNA panel was slightly higher in the HER2 and TN compared to patients with luminal subtype. Therefore, we developed a novel approach which led to the identification of a novel microRNA panel which was upregulated in BC patients with potential utilization in disease diagnosis and stratification.
Stem Cell Research & Therapy, Jul 24, 2015
Introduction: Tumor microenvironment conferred by stromal (mesenchymal) stem cells (MSCs) plays a... more Introduction: Tumor microenvironment conferred by stromal (mesenchymal) stem cells (MSCs) plays a key role in tumor development, progression, and response to therapy. Defining the role of MSCs in tumorigenesis is crucial for their safe utilization in regenerative medicine. Herein, we conducted comprehensive investigation of the cross-talk between human MSCs (hMSCs) and 12 cancer cell lines derived from breast, prostate, colon, head/neck and skin. Methods: Human bone marrow-derived MSC line expressing green fluorescence protein (GFP) (hMSC-GFP) were co-cultured with the following cancer cell lines: (MCF7, BT-20, BT-474, MDA-MB-468, T-47D, SK-BR-3, MDA-MB-231, PC-3, HT-29, MDA-MB-435s, and FaDu) and changes in their morphology were assessed using fluorescent microscopy. For cellular tracking, cells were labeled with Vybrant DiO, DiL, and DiD lipophilic dyes. Time-lapse microscopy was conducted using Nikon BioStation IM-Q. Stable expression of mCherry, and luciferase genes was achieved using lentiviral technology. IL1-Beta neutralizing experiments were conducted using soluble recombinant IL-1R (srIL-1R). Changes in gene expression in sorted hMSCs were assessed using Agilent microarray platform while data normalization and bioinformatics were conducted using GeneSpring software. Results: We observed a dynamic interaction between cancer cells and hMSCs. High CDH1 (E-cadherin) and low IL1-Beta expression by cancer cells promoted reorganization of hMSCs into a niche-like formation, which was dependent on direct cell-cell contact. Our data also revealed transfer of cellular components between cancer cells and hMSCs as one possible mechanism for intercellular communication. Global gene expression analysis of sorted hMSCs following co-culturing with MCF7 and BT-20 cells revealed enrichment in signaling pathways related to bone formation, FAK and MAPKK signaling. Co-culturing hMSCs with MCF7 cells increased their growth evidenced by increase in Ki67 and PCNA staining in tumor cells in direct contact with hMSCs niche. On the other hand, co-culturing hMSCs with FaDu, HT-29 or MDA-MB-231 cells led remarkable decline in their cell growth.
Journal of Nanoscience and Nanotechnology, Mar 1, 2017
Stem cell biology and regenerative medicine, 2016
Human skeletal stem cells (also known as bone marrow-derived stromal cells, hBMSCs) are adult clo... more Human skeletal stem cells (also known as bone marrow-derived stromal cells, hBMSCs) are adult clonogenic cells located in a perivascular niche in the bone marrow. hBMSCs are capable of multilineage differentiation into various mesoderm-cell types including bone forming osteoblastic cells. A number of stromal stem cells (MSCs) have also been isolated from the stroma of different tissues and share some characteristics with BMSCs. Due to their ease of isolation and multi-linage differentiation potential, hBMSCs are being introduced into clinical medicine for treatment of a variety of degenerative diseases. In this chapter, we discuss the bone regenerative capacity of BMSCs as relevant to their use in regenerating skeletal tissues.
Folia Morphologica, Sep 2, 2015
This study was performed to investigate the effect of curcumin on cardiac myosin-induced autoimmu... more This study was performed to investigate the effect of curcumin on cardiac myosin-induced autoimmune myocarditis in rats and the change in thioredoxin (TRX) immunoreactivity in cardiomyocytes following curcumin treatment. Twenty-four six-week-old male Wistar rats were randomly allocated into 4 groups of 6 rats each. Group I received neither curcumin nor myosin. Group II received an oral solution of 1 g/kg/day of curcumin daily, from day 1 to day 21. To induce myocarditis, animals of both group III and group IV were injected by 1 mg of porcine cardiac myosin on days 1 and 8. In addition, animals of group IV received an oral solution of 1 g/kg/day of curcumin daily, from day 1 to day 21. Serum levels of creatine phosphokinase, troponin-T, tumour necrosis factor-alpha and interleukin-6 were estimated. Hearts were processed for histopathological and immunohistochemical studies. Serum biomarkers levels were significantly increased in myocarditis group as compared to other groups. The intake of curcumin significantly reduced the deviation in these markers. Sections of the wall of the heart from myocarditis group were characterised by inflammatory cell infiltration. Most of cardiomyocytes showed pyknotic nuclei and increased sarcoplasmic eosinophilia with strong immunoreactivity for TRX. Sections from myocarditis-curcumin group showed normal architecture with moderate immunoreactivity for TRX. The present study demonstrated that curcumin ameliorates acute myocarditis in rats and encouraged the estimation of serum level of TRX as a relevant indicator for the evaluation of the progress of acute myocarditis.
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Papers by Abdullah Aldahmash