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  1. The effects of human serum to the morphology, proliferation and gene expression level of the respiratory epithelium in vitro
    Yunus MH, Siang KC, Hashim NI, Zhi NP, Zamani NF, Sabri PP, et al.
    Tissue Cell, 2014 Aug;46(4):233-40.
    PMID: 24973262 DOI: 10.1016/j.tice.2014.05.003
    The culture of human airway epithelial cells has played an important role in advancing our understanding of the metabolic and molecular mechanisms underlying normal function and disease pathology of airway epithelial cells. The present study focused on investigating the effects of human serum (HS) on the qualitative and quantitative properties of the human respiratory epithelium compared to the fetal bovine serum (FBS), as a supplement in culture. Respiratory epithelial (RE) cells derived from human nasal turbinate were co-cultured with fibroblasts, subsequently separated at 80-90% confluency by differential trypsinization. RE cells were then sub-cultured into 2 different plates containing 5% allogenic HS and FBS supplemented media respectively up to passage 1 (P1). Cell morphology, growth rate, cell viability and population doubling time were assessed under light microscope, and levels of gene expression were measured via real time reverse transcriptase-polymerase chain reaction (qRT-PCR). RE cells appeared as polygonal shape and expanded when cultured in HS whereas RE cells in FBS were observed to be easily matured thus limit the RE cells expansion. Proliferation rate of RE cells in HS supplemented media (7673.18 ± 1207.15) was 3 times higher compared to RE in FBS supplemented media (2357.68 ± 186.85). Furthermore, RE cells cultured in HS-supplemented media required fewer days (9.15 ± 1.10) to double in numbers compared to cells cultured in FBS-supplemented media (13.66 ± 0.81). Both the differences were significant (p<0.05). However, there were no significant differences in the viability of RE cells in both groups (p=0.105). qRT-PCR showed comparable expressions of gene Cytokeratin-14 (CK-14), Cytokeratin-18 (CK-18) and Mucin-5 subtype B (MUC5B) in RE cells cultured in both groups (p>0.05). In conclusion, HS is a comparatively better choice of media supplement in accelerating growth kinetics of RE cells in vitro thus producing a better quality of respiratory epithelium for future tracheal reconstruction.
  2. Posterolateral spinal fusion with ostegenesis induced BMSC seeded TCP/HA in a sheep model
    Shamsul BS, Tan KK, Chen HC, Aminuddin BS, Ruszymah BH
    Tissue Cell, 2014 Apr;46(2):152-8.
    PMID: 24630213 DOI: 10.1016/j.tice.2014.02.001
    Autogenous bone graft is the gold standard for fusion procedure. However, pain at donor site and inconsistent outcome have left a surgeon to venture into some other technique for spinal fusion. The objective of this study was to determine whether osteogenesis induced bone marrow stem cells with the combination of ceramics granules (HA or TCP/HA), and fibrin could serve as an alternative to generate spinal fusion. The sheep's bone marrow mesenchymal stem cells (BMSCs) were aspirated form iliac crest and cultured for several passages until confluence. BMSCs were trypsinized and seeded on hydroxyapatite scaffold (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) for further osteogenic differentiation in the osteogenic medium one week before implantation. Six adult sheep underwent three-level, bilateral, posterolateral intertransverse process fusions at L1-L6. Three fusion sites in each animal were assigned to three treatments: (a) HA constructs group/L1-L2, (b) TCP/HA constructs group/L2-L3, and (c) autogenous bone graft group/L5-L6. The spinal fusion segments were evaluated using radiography, manual palpation, histological analysis and scanning electron microscopy (SEM) 12 weeks post implantation. The TCP/HA constructs achieved superior lumbar intertransverse fusion compared to HA construct but autogenous bone graft still produced the best fusion among all.
  3. Human mesenchymal stromal cells could deliver erythropoietin and migrate to the basal layer of hair shaft when subcutaneously implanted in a murine model
    Mok PL, Cheong SK, Leong CF, Chua KH, Ainoon O
    Tissue Cell, 2012 Aug;44(4):249-56.
    PMID: 22560724 DOI: 10.1016/j.tice.2012.04.002
    Mesenchymal stromal cells (MSC) are an attractive cell-targeting vehicle for gene delivery. MIDGE (an acronym for Minimalistic, Immunologically Defined Gene Expression) construct is relatively safer than the viral or plasmid expression system as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. The objective of this study was to test the ability of the human MSC (hMSC) to deliver the erythropoietin (EPO) gene in a nude mice model following nucleofection using a MIDGE construct. hMSC nucleofected with MIDGE encoding the EPO gene was injected subcutaneously in Matrigel at the dorsal flank of nude mice. Subcutaneous implantation of nucleofected hMSC resulted in increased hemoglobin level with presence of human EPO in the peripheral blood of the injected nude mice in the first two weeks post-implantation compared with the control groups. The basal layer of the hair shaft in the dermal layer was found to be significantly positive for immunohistochemical staining of a human EPO antibody. However, only a few basal layers of the hair shaft were found to be positively stained for CD105. In conclusion, hMSC harboring MIDGE-EPO could deliver and transiently express the EPO gene in the nude mice model. These cells could be localized to the hair follicle and secreted EPO protein might have possible role in hair regeneration.
  4. Bone marrow and adipose stem cells can be tracked with PKH26 until post staining passage 6 in in vitro and in vivo
    Ude CC, Shamsul BS, Ng MH, Chen HC, Norhamdan MY, Aminuddin BS, et al.
    Tissue Cell, 2012 Jun;44(3):156-63.
    PMID: 22402173 DOI: 10.1016/j.tice.2012.02.001
    Tracking of transplanted cells has become an important procedure in cell therapy. We studied the in vitro dye retention, survival and in vivo tracking of stem cells with PKH26 dye. Sheep BMSCs and ADSCs were labeled with 2, 4 and 8 μmol of PKH26 and monitored for six passages. Labeled BMSCs and ADSCs acquired mean cumulative population doubling of 12.7±0.4 and 14.6±0.5; unlabeled samples had 13.8±0.5 and 15.4±0.6 respectively. Upon staining with 2, 4 and 8 μmol PKH26, BMSCs had retentions of 40.0±5.8, 60.0±2.9 and 95.0±2.9%, while ADSCs had 92.0±1.2, 95.0±1.2 and 98.0±1.2%. ADSCs retentions were significantly higher at 2 and 4 μmol. On dye retention comparison at 8 μmol and 4 μmol for BMSCs and ADSCs; ADSCs were significantly higher at passages 2 and 3. The viability of BMSCs reduced from 94.0±1.2% to 90.0±0.6% and ADSCs from 94.0±1.2% to 52.0±1.2% (p<0.05) after 24h. BMSCs had significant up regulation of the cartilage genes for both the labeled and the unlabeled samples compared to ADSCs (p<0.05). PKH26 fluorescence was detected on the resected portions of the regenerated neo-cartilage. The recommended concentration of PKH26 for ADSCs is 2 μmol and BMSCs is 8 μmol, and they can be tracked up to 49 days.
  5. Expansion of human articular chondrocytes and formation of tissue-engineered cartilage: a step towards exploring a potential use of matrix-induced cell therapy
    Munirah S, Samsudin OC, Aminuddin BS, Ruszymah BH
    Tissue Cell, 2010 Oct;42(5):282-92.
    PMID: 20810142 DOI: 10.1016/j.tice.2010.07.002
    Monolayer culture expansion remains as a fundamental step to acquire sufficient number of cells for 3D constructs formation. It has been well-documented that cell expansion is however accompanied by cellular dedifferentiation. In order to promote cell growth and circumvent cellular dedifferentiation, we evaluated the effects of Transforming Growth Factor Beta-2 (TGF-β2), Insulin-like Growth Factor-I (IGF-I) and basic Fibroblast Growth Factor (bFGF) combination on articular chondrocytes culture and 'chondrocytes-fibrin' construct formation. Chondrocytes were serially cultured in: (1) F12:DMEM+10% Foetal Bovine Serum (FBS) with growth factors (FD10GFs), (2) F12:DMEM+2%FBS with the growth factors (FD2GFs) and, (3) F12:DMEM+10%FBS without growth factors (FD) as control. Cultured chondrocytes were evaluated by means of growth kinetics parameters, cell cycle analysis, quantitative phenotypic expression of collagen type II, aggrecan core protein sox-9 and collagen type I and, immunochemistry technique. Harvested chondrocytes were incorporated with plasma-derived fibrin and were polymerized to form the 3D constructs and implanted subcutaneously at the dorsum of athymic nude mice for eight (8) weeks. Resulted constructs were assigned for gross inspections and microscopic evaluation using standard histochemicals staining, immunochemistry technique and, quantitative phenotypic expression of cartilage markers to reassure cartilaginous tissue formation. Growth kinetics performance of chondrocytes cultured in three (3) types of culture media from the most to least was in the following order: FD10GFs>FD2GFs>FD. Following growth kinetics analysis, we decided to use FD10GFs and FD (control) for further evaluation and 'chondrocytes-fibrin' constructs formation. Chondrocytes cultured in FD10GFs preserved the normal diploid state (2c) with no evidence of aneuploidy, haploidy or tetraploidy. Expression of cartilage-specific markers namely collagen type II, aggrecan core protein and sox-9 were significantly higher in FD10GFs when compared to control. After implantation, 'chondrocytes-fibrin' constructs exhibited firm, white, smooth and glistening cartilage-like properties. FD10GFs constructs formed better quality cartilage-like tissue than FD constructs in term of overall cartilaginous tissue formation, cells organization and extracellular matrix distribution in the specimens. Cartilaginous tissue formation was confirmed by the presence of lacunae and cartilage-isolated cells embedded within basophilic ground substance. Presence of proteoglycan was confirmed by positive Safranin O staining. Collagen type II exhibited immunopositivity at the pericellular and inter-territorial matrix area. Chondrogenic properties of the construct were further confirmed by the expression of genes encoding collagen type II, aggrecan core protein and sox9. In conclusion, FD10GFs promotes the proliferation of chondrocytes and formation of good quality 'chondrocytes-fibrin' constructs which may have potential use of matrix-induced cell implantation.
  6. Induction of pluripotency in human umbilical cord mesenchymal stem cells in feeder layer-free condition
    Daneshvar N, Rasedee A, Shamsabadi FT, Moeini H, Mehrboud P, Rahman HS, et al.
    Tissue Cell, 2015 Dec;47(6):575-82.
    PMID: 26471847 DOI: 10.1016/j.tice.2015.04.005
    Induced Pluripotent Stem Cells (iPSCs) has been produced by the reprogramming of several types of somatic cells through the expression of different sets of transcription factors. This study consists of a technique to obtain iPSCs from human umbilical cord mesenchymal stem cells (UC-MSCs) in a feeder layer-free process using a mini-circle vector containing defined reprogramming genes, Lin28, Nanog, Oct4 and Sox2. The human MSCs transfected with the minicircle vector were cultured in iPSCs medium. Human embryonic stem cell (ESC)-like colonies with tightly packed domelike structures appeared 7-10 days after the second transfection. In the earliest stages, the colonies were green fluorescence protein (GFP)-positive, while upon continuous culture and passage, genuine hiPSC clones expressing GFP were observed. The induced cells, based on the ectopic expression of the pluripotent markers, exhibited characteristics similar to the embryonic stem cells. These iPSCs demonstrated in vitro capabilities for differentiation into the three main embryonic germ layers by embryoid bodies formation. There was no evidence of transgenes integration into the genome of the iPSCs in this study. In conclusion, this method offers a means of producing iPSCs without viral delivery that could possibly overcome ethical concerns and immune rejection in the use of stem cells in medical applications.
  7. The potential of 3-dimensional construct engineered from poly(lactic-co-glycolic acid)/fibrin hybrid scaffold seeded with bone marrow mesenchymal stem cells for in vitro cartilage tissue engineering
    Abdul Rahman R, Mohamad Sukri N, Md Nazir N, Ahmad Radzi MA, Zulkifly AH, Che Ahmad A, et al.
    Tissue Cell, 2015 Aug;47(4):420-30.
    PMID: 26100682 DOI: 10.1016/j.tice.2015.06.001
    Articular cartilage is well known for its simple uniqueness of avascular and aneural structure that has limited capacity to heal itself when injured. The use of three dimensional construct in tissue engineering holds great potential in regenerating cartilage defects. This study evaluated the in vitro cartilaginous tissue formation using rabbit's bone marrow mesenchymal stem cells (BMSCs)-seeded onto poly(lactic-co-glycolic acid) PLGA/fibrin and PLGA scaffolds. The in vitro cartilaginous engineered constructs were evaluated by gross inspection, histology, cell proliferation, gene expression and sulphated glycosaminoglycan (sGAG) production at week 1, 2 and 3. After 3 weeks of culture, the PLGA/fibrin construct demonstrated gross features similar to the native tissue with smooth, firm and glistening appearance, superior histoarchitectural and better cartilaginous extracellular matrix compound in concert with the positive glycosaminoglycan accumulation on Alcian blue. Significantly higher cell proliferation in PLGA/fibrin construct was noted at day-7, day-14 and day-21 (p<0.05 respectively). Both constructs expressed the accumulation of collagen type II, collagen type IX, aggrecan and sox9, showed down-regulation of collagen type I as well as produced relative sGAG content with PLGA/fibrin construct exhibited better gene expression in all profiles and showed significantly higher relative sGAG content at each time point (p<0.05). This study suggested that with optimum in vitro manipulation, PLGA/fibrin when seeded with pluripotent non-committed BMSCs has the capability to differentiate into chondrogenic lineage and may serve as a prospective construct to be developed as functional tissue engineered cartilage.
  8. Generation of induced pluripotent stem cells by a polycistronic lentiviral vector in feeder- and serum- free defined culture
    Al Abbar A, Nordin N, Ghazalli N, Abdullah S
    Tissue Cell, 2018 Dec;55:13-24.
    PMID: 30503056 DOI: 10.1016/j.tice.2018.09.004
    Induced pluripotent stem cells (iPSCs) have great potentials for regenerative medicine. However, serious concerns such as the use of the viral-mediated reprogramming strategies and exposure of iPSCs to animal products from feeder cells and serum-containing medium have restricted the application of iPSCs in the clinics. Therefore, the generation of iPSCs with minimal viral integrations and in non-animal sourced and serum-free medium is necessary. In this report, a polycistronic lentiviral vector carrying Yamanaka's factors was used to reprogram mouse fibroblasts into iPSCs in feeder- and xeno-free culture environment. The generated iPSCs exhibited morphology and self-renewal properties of embryonic stem cells (ESCs), expression of specific pluripotent markers, and potentials to differentiate into the three-major distinct specialized germ layers in vitro. The iPSCs were also shown to have the potential to differentiate into neural precursor and neurons in culture, with greater than 95% expression of nestin, Pax6 and βIII-tubulin. This body of work describes an alternative method of generating iPSCs by using polycistronic lentiviral vector that may minimize the risks associated with viral vector-mediated reprogramming and animal derived products in the culture media.
  9. Impact of dengue virus (serotype DENV-2) infection on liver of BALB/c mice: A histopathological analysis
    Sakinah S, Priya SP, Kumari S, Amira F, K P, Alsaeedy H, et al.
    Tissue Cell, 2017 Feb;49(1):86-94.
    PMID: 28034555 DOI: 10.1016/j.tice.2016.11.005
    In this research, we characterized the histopathological impact of dengue virus (serotype DENV-2) infection in livers of BALB/c mice. The mice were infected with different doses of DENV-2 via intraperitoneal injection and liver tissues were processed for histological analyses and variation was documented. In the BALB/c mouse model, typical liver tissues showed regular hepatocyte architecture, with normal endothelial cells surrounding sinusoid capillary. Based on histopathological observations, the liver sections of BALB/c mice infected by DENV-2 exhibited a loss of cell integrity, with a widening of the sinusoidal spaces. There were marked increases in the infiltration of mononuclear cells. The areas of hemorrhage and micro- and macrovesicular steatosis were noted. Necrosis and apoptosis were abundantly present. The hallmark of viral infection, i.e., cytopathic effects, included intracellular edema and vacuole formation, cumulatively led to sinusoidal and lobular collapse in the liver. The histopathological studies on autopsy specimens of fatal human DENV cases are important to shed light on tissue damage for preventive and treatment modalities, in order to manage future DENV infections. In this framework, the method present here on BALB/c mouse model may be used to study not only the effects of infections by other DENV serotypes, but also to investigate the effects of novel drugs, such as recently developed nano-formulations, and the relative recovery ability with intact immune functions of host.
  10. Mesenchymal stem cells for cartilage regeneration: Insights into molecular mechanism and therapeutic strategies
    Mamachan M, Sharun K, Banu SA, Muthu S, Pawde AM, Abualigah L, et al.
    Tissue Cell, 2024 Apr 10;88:102380.
    PMID: 38615643 DOI: 10.1016/j.tice.2024.102380
    The use of mesenchymal stem cells (MSCs) in cartilage regeneration has gained significant attention in regenerative medicine. This paper reviews the molecular mechanisms underlying MSC-based cartilage regeneration and explores various therapeutic strategies to enhance the efficacy of MSCs in this context. MSCs exhibit multipotent capabilities and can differentiate into various cell lineages under specific microenvironmental cues. Chondrogenic differentiation, a complex process involving signaling pathways, transcription factors, and growth factors, plays a pivotal role in the successful regeneration of cartilage tissue. The chondrogenic differentiation of MSCs is tightly regulated by growth factors and signaling pathways such as TGF-β, BMP, Wnt/β-catenin, RhoA/ROCK, NOTCH, and IHH (Indian hedgehog). Understanding the intricate balance between these pathways is crucial for directing lineage-specific differentiation and preventing undesirable chondrocyte hypertrophy. Additionally, paracrine effects of MSCs, mediated by the secretion of bioactive factors, contribute significantly to immunomodulation, recruitment of endogenous stem cells, and maintenance of chondrocyte phenotype. Pre-treatment strategies utilized to potentiate MSCs, such as hypoxic conditions, low-intensity ultrasound, kartogenin treatment, and gene editing, are also discussed for their potential to enhance MSC survival, differentiation, and paracrine effects. In conclusion, this paper provides a comprehensive overview of the molecular mechanisms involved in MSC-based cartilage regeneration and outlines promising therapeutic strategies. The insights presented contribute to the ongoing efforts in optimizing MSC-based therapies for effective cartilage repair.
  11. In vivo assessment of reversing aminoglycoside antibiotics nephrotoxicity using Jatropha mollissima crude extract
    Iqbal MO, Yahya EB
    Tissue Cell, 2021 Oct;72:101525.
    PMID: 33780659 DOI: 10.1016/j.tice.2021.101525
    Aminoglycoside antibiotics are widely employed clinically due to their powerful bactericidal activities, less bacterial resistance compared to beta lactam group and low cost. However, their use has been limited in recent years due to their potential induction of nephrotoxicity. Here we investigate the possibility of reversing nephrotoxicity caused by gentamicin in rat models by using ethanolic crude extract of the medicinal plant Jatropha Mollissima. Nephrotoxic male Wistar rats was obtained by gentamicin antibiotic, which then treated with two doses of J. mollissima crude extract for 3 weeks with monitoring their parameter in weekly base. Our results indicate that J. mollissima crude extract at both doses has strong protection ability against gentamicin nephrotoxicity, most of tested parameters backed to normal values after few days from the administration of the crude extract, which could be due to the antagonized the biochemical action of gentamicin on the proximal tubules of the kidney. The results of histopathologic analysis showed observable improvement in J. mollissima treated groups compared with untreated groups. Our findings suggests the J. mollissima has exceptional nephron protection potentials able to reverse the nephrotoxicity caused by gentamicin antibiotic.
  12. The potential mechanism of hypoxia-induced tenogenic differentiation of mesenchymal stem cell for tendon regeneration
    Zulkifli A, Ahmad RE, Krishnan S, Kong P, Nam HY, Kamarul T
    Tissue Cell, 2023 Jun;82:102075.
    PMID: 37004269 DOI: 10.1016/j.tice.2023.102075
    Tendon injuries account up to 50% of all musculoskeletal problems and remains a challenge to treat owing to the poor intrinsic reparative ability of tendon tissues. The natural course of tendon healing is very slow and often leads to fibrosis and disorganized tissues with inferior biomechanical properties. Mesenchymal stem cells (MSC) therapy is a promising alternative strategy to augment tendon repair due to its proliferative and multilineage differentiation potential. Hypoxic conditioning of MSC have been shown to enhance their tenogenic differentiation capacity. However, the mechanistic pathway by which this is achieved is yet to be fully defined. A key factor involved in this pathway is hypoxia-inducible factor-1-alpha (HIF-1α). This review aims to discuss the principal mechanism underlying the enhancement of MSC tenogenic differentiation by hypoxic conditioning, particularly the central role of HIF-1α in mediating activation of tenogenic pathways in the MSC. We focus on the interaction between HIF-1α with fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta 1 (TGF-β1) in regulating MSC tenogenic differentiation pathways in hypoxic conditions. Strategies to promote stabilization of HIF-1α either through direct manipulation of oxygen tension or the use of hypoxia mimicking agents are therefore beneficial in increasing the efficacy of MSC therapy for tendon repair.
  13. Histological characterization of pulp regeneration using decellularized human dental pulp and mesenchymal stem cells in a feline model
    Tan YY, Abdullah D, Abu Kasim NH, Yazid F, Mahamad Apandi NI, Ramanathan A, et al.
    Tissue Cell, 2024 Oct;90:102484.
    PMID: 39068688 DOI: 10.1016/j.tice.2024.102484
    Regenerative endodontics aims to restore pulp tissues, thus preserving the vitality of the tooth. One promising approach involves the utilization of decellularized human dental pulp (DHDP) as a scaffold repopulated with Wharton's Jelly mesenchymal stem cells (WJMSCs). This study aimed to regenerate pulp tissues using DHDP and WJMSCs following pulpectomy in mature canine teeth of a feline animal model and to investigate the histological features of the regenerated pulp. A 12-month-old male domestic shorthaired felines were used as subjects. Teeth were categorized into untreated (Group 1), pulpectomy with mineral trioxide aggregate (MTA) (Group 2), and pulpectomy with DHDP-repopulated scaffold and MTA (Group 3). The animals were sacrificed six weeks post-intervention. H&E and immunohistochemistry using anti-collagen type 1 and laminin antibodies were used to stain the tissue sections. Histological examinations presented pulp-like tissues in Group 3, with tissue components similar to the structures found in Group 1. Immunohistochemical analysis demonstrated the presence of collagen type I and laminin within the regenerated tissues. The root canals of teeth in Group 2 were devoid of pulpal tissue. DHDP with WJMSCs can potentially be used for pulp regeneration, supporting the modality for developing new clinical protocols in stem cell therapy.
  14. The limelight of adipose-derived stem cells in the landscape of neural tissue engineering for peripheral nerve injury
    QingNing S, Mohd Ismail ZI, Ab Patar MNA, Mat Lazim N, Hadie SNH, Mohd Noor NF
    Tissue Cell, 2024 Dec;91:102556.
    PMID: 39293138 DOI: 10.1016/j.tice.2024.102556
    Challenges in treating peripheral nerve injury include prolonged repair time and insufficient functional recovery. Stem cell therapy coupled with neural tissue engineering has been shown to induce nerve regeneration following peripheral nerve injury. Among these stem cells, adipose-derived stem cells (ADSCs) are preferred due to their accessibility, expansion, multidirectional differentiation, and production of essential nutrient factors for nerve growth. In recent years, ADSC-laden nerve guide conduit has been utilized to enhance the therapeutic effects of tissue-engineered nerve grafts. This review explores existing research that recognizes the roles played by ADSCs in inducing peripheral nerve regeneration following injury and summarizes the different methods of application of ADSC-laden nerve conduit in neural tissue engineering.
  15. Malaria parasite detection in Red Blood Cells with rouleaux formation morphology using YOLOv9
    Muhammad FA, Sudirman R, Zakaria NA
    Tissue Cell, 2025 Apr;93:102677.
    PMID: 39719819 DOI: 10.1016/j.tice.2024.102677
    Malaria is endemic in poverty-stricken regions of the world, and most diagnosis reveal comorbidity with other infectious diseases some of which manifest as a deformity of the structural arrangement of the Red Blood Cells (RBCs) during thin blood smear microscopy. This common occurring deformity is termed rouleaux formation, and it is the stacking together of RBCs like chains of coins. The presence of rouleaux formation indicates either a bacterial infection, connective tissue disease, chronic liver disease, multiple myeloma or diabetes among others, it is a highly common occurrence in malaria infected patients and according to the international council for standardization of hematology (ICSH), microscopists are mandated to report its presence. Hence to develop unbiased automated malaria diagnostic systems capable of being deployed in malaria endemic regions, these systems need to be capable of identifying rouleaux formation and detecting malaria parasite within such type of RBC. Thus, this study developed a thin blood smear dataset with rouleaux formation RBCs infected with two species of malaria parasite: plasmodium falciparum and plasmodium malariae. YOLOv9s architecture was used to benchmark the dataset for the detection of plasmodium parasites and white blood cells in the developed dataset. Comparing the effect of using pretrained weights, YOLOv9s trained from scratch achieved a Precision, Recall and mAP50 of 75.4 %, 76.6 % and 80.3 % while YOLOv9s pretrained on the MS COCO dataset recorded an improvement in performance metrics with an increase in Precision by 0.4 %, an increase in Recall by 5.4 % and an increase in mAP50 by 2.5 .
  16. Comparative Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs): Difference in effect of aspirin on osteoblast potential of PDLSCs and DPSCs
    Abd Rahman F, Azwa FN
    Tissue Cell, 2025 Jun;94:102776.
    PMID: 40022908 DOI: 10.1016/j.tice.2025.102776
    Periodontal Ligament Stem Cells (PDLSCs) and Dental Pulp Stem Cells (DPSCs) are mesenchymal stem cells with the ability to self-renew and differentiate into three lineages. One significant advantage of dental stem cells, such as PDLSCs and DPSCs, is their ease of harvest compared to other types of mesenchymal stem cells (MSCs). While MSCs are highly valued in bone tissue engineering, MSCs sourced from dental tissues, such as PDLSCs and DPSCs, offer promising options for periodontal regeneration because they are more easily accessible and can be collected through minimally invasive methods. Currently, PDLSCs and DPSCs exhibit a strong ability to undergo osteogenic differentiation when stimulated by factors such as growth factors, chemicals, and paracrine signaling. It has been shown that aspirin (ASA) can enhance the osteoblastic potential of PDLSCs and DPSCs, although the exact mechanism remains unclear. This article examines the origin and features of mesenchymal stem cells, the bone regeneration potential of DPSCs and PDLSCs, the factors that enhance their osteogenic differentiation, and a comparison of PDLSCs and DPSCs regarding their proliferation and differentiation abilities. Additionally, we will examine the effects of aspirin on PDLSCs and DPSCs. In conclusion, PDLSCs show a greater effect on osteoblast differentiation.
  17. Roxadustat pre-conditioning and cyclic uniaxial stretching improve tenogenic differentiation potential of human adipose derived mesenchymal stromal cells
    Zulkifli A, Nam HY, Ng WM, Yasin NF, Kamarul T
    Tissue Cell, 2025 Feb 27;95:102828.
    PMID: 40086111 DOI: 10.1016/j.tice.2025.102828
    Tendon injuries represent a significant challenge to treat owing to their limited intrinsic reparative capacity. The use of mesenchymal stem cells (MSC) offers promising alternative therapeutic option to augments tendon repair. It is hypothesised that the activation of hypoxia inducible factor-1 alpha (HIF-1α), could facilitate the tendon repair process by promoting the proliferation and tenogenic differentiation of MSCs. To demonstrate this, a study was conducted incorporating the use of Roxadustat, a specific hypoxia mimetic mediator and cyclic uniaxial stretching at a frequency of 1 Hz and 8 % strain on adipose derived-mesenchymal stromal cells (ADMSCs).

    METHODS: Cellular morphology, proliferation rate, tenogenic protein and gene expression levels from 8 different treatment groups were compared. These groups include untreated ADMSCs (Control), Roxadustat pre-conditioned ADMSCs (ROX), ADMSCs subjected CAY10585 treatment only (CAY), Roxadustat pre-conditioned ADMSCs with CAY10585 inhibition (ROX+CAY), ADMSCs subjected to uniaxial stretching only (S), Roxadustat pre-conditioned ADMSCs with uniaxial stretching (ROX+S), ADMSCs subjected CAY10585 with uniaxial stretching (CAY+S) and primary tenocytes (Tenocytes).

    RESULTS: ROX+S group exhibited the highest expression of HIF-1α and demonstrated a significant up-regulation of collagen I and III expressions, increasing by 4.9 and 5.6-fold compared to ROX group, respectively. There is a significant increase of SCX, TNC, TNMD, COLI and COLIII expression in this combination treatment group; (SCX= 9.9, TNC= 12.6, TNMD= 7.0, COLI= 8.0 and COLIII= 10.0-fold). Conversely, the expression of the markers markedly reduced with HIF-1α inhibitor CAY10585. However, uniaxial stretching effectively counteracted the inhibitory effects of CAY10585 in the CAY+ S group, resulting in a 3.9-fold increase in SCX expression compared to CAY treatment alone.

    CONCLUSION: HIF-1α accumulation promotes superior tenogenic differentiation of ADMSCs, suggesting that the combination of Roxadustat and cyclic uniaxial stretching may be a potential therapeutic mediator in tendon repair strategies.

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