Papers by Adetola Adesida
Cell communication and signaling, Jun 21, 2024
Background Mechanical unloading of the knee articular cartilage results in cartilage matrix atrop... more Background Mechanical unloading of the knee articular cartilage results in cartilage matrix atrophy, signifying the osteoarthritic-inductive potential of mechanical unloading. In contrast, mechanical loading stimulates cartilage matrix production. However, little is known about the response of meniscal fibrocartilage, a major mechanical load-bearing tissue of the knee joint, and its functional matrix-forming fibrochondrocytes to mechanical unloading events. In this study, primary meniscus fibrochondrocytes isolated from the inner avascular region of human menisci from both male and female donors were seeded into porous collagen scaffolds to generate 3D meniscus models. These models were subjected to both normal gravity and mechanical unloading via simulated microgravity (SMG) for 7 days, with samples collected at various time points during the culture. Results RNA sequencing unveiled significant transcriptome changes during the 7-day SMG culture, including the notable upregulation of key osteoarthritis markers such as COL10A1, MMP13, and SPP1, along with pathways related to inflammation and calcification. Crucially, sex-specific variations in transcriptional responses were observed. Meniscus models derived from female donors exhibited heightened cell proliferation activities, with the JUN protein involved in several potentially osteoarthritis-related signaling pathways. In contrast, meniscus models from male donors primarily regulated extracellular matrix components and matrix remodeling enzymes. These findings advance our understanding of sex disparities in knee osteoarthritis by developing a novel in vitro model using cell-seeded meniscus constructs and simulated microgravity, revealing significant sex-specific molecular mechanisms and therapeutic targets.
Orthopaedic Proceedings, 2011
Objective: To investigate neurological effects of transplanting bone marrow-derived mesenchymal s... more Objective: To investigate neurological effects of transplanting bone marrow-derived mesenchymal stem cells (BMSCs) transfected with the basic fibroblast growth factor (bFGF) gene in spinal cord-injured rats. Methods: Ninety-six male adult Sprague-Dawley rats were randomized into four groups: (1) pcDNA3.1-bFGF group; (2) pcDNA3.1 group; (3) BMSCs group; and (4) vehicle control (DMEM) group. After the rat model of acute spinal cord injury (SCI) was established, 1610 6 BMSCs or cells transfected with pcDNA3.1-bFGF or pcDNA3.1 were injected into rats of groups 1-3. At days 1, 7, 14, and 21 after injection, the Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to evaluate recovery of motor function. Expression changes of bFGF, myelin basic protein (MBP), and NF200 were examined by immunohistochemistry. Results: The BBB score of DMEM group was significantly lower than those of groups 1-3 (P,0.05), but the score of pcDNA3.1-bFGF group was significantly higher than that of BMSCs group or pcDNA3.1 group at day 14 or 21 after injection (P,0.01). The number of bFGF-positive neurons in rats of pcDNA3.1-bFGF group was significantly higher than those of groups 1-3 at any time point (P,0.05). The optical density values of NF200-positive neurons and MBP-positive MBP axons in rats of pcDNA3.1-bFGF group were significantly higher than those of groups 1-3 at day 7 or 14 after injection (P,0.05). Conclusions: bFGF gene-modified BMSCs not only effectively promoted axonal outgrowth but also enhanced recovery of neurological function after SCI in rats, and may be a good candidate to evaluate gene therapy of SCI in man.
American Journal of Physiology-cell Physiology, Dec 1, 2022
Stem cells in clinical applications, 2016
Mesenchymal stem cells (MSCs) have a great capacity for use in regenerative medicine and other cl... more Mesenchymal stem cells (MSCs) have a great capacity for use in regenerative medicine and other clinical applications. However, one question creating curiosity of their use, is how they are affected by ageing. As we now live within an ageing population, the prevalence of age related disorders is increasing, so it is important to investigate how effectively MSCs from older patients can be expanded and differentiated in vitro before their use in autologous cell transplantation. This paper will look at how ageing effects proliferation potential, differentiation potential and cell surface characterisation of human mesenchymal stem cells.
Leukemia Research, 1996
Abatraet-hlercapturic acid pathway metabolites of phenylethyl isothiocyanate inhibited the growth... more Abatraet-hlercapturic acid pathway metabolites of phenylethyl isothiocyanate inhibited the growth of human leukaemia 60 (HL60) cells in vitro. The adduct with L-cysteine, S-(N-phenylethylthiocarbamoyl)cysteine, was the most potent with strong antileukaemic activity: the median growth inhibitory concentration (GC,) value was 336 & 1 nM (N = 18) compared with GC, values of the precursor formed from dietary glucosinolates, phenylethyl isothiocyanate, 1.49 + 0.01 PM (N = 8), and the initial mercapturic acid pathway metabolite S-(N-pheny1ethylthiocarbamoyl)glutathione 5.46 f 0.36 PM (N = 18). S-(N-Benzylthiocarbamoyl)cysteine and S-(N-phenylpropylthiocarbamoyl)cysteine also had antiproliferative activipr but S-(N-phenylethylthiocarbamoyl)cysteine was the most potent compound studied. The latter induced DNA fragmentation in HL60 cells but DNA laddering characteristic of apoptosis was not observed. It had low toxicity to corresponding differentiated cells, neutrophils, in culture, and therefore the cytotoxilcity had selectivity for leukaemia cells. The antiproliferative activity of S-(N-phenylethylthiocarbamoyl)cysteine was lost during preincubation with culture medium, attributed to S-thiocarbamoyl transfer to serum proteins, which may decrease its effectiveness in viuo. The antiproliferative activity of S-(N-phenylalkylthiocarbamoyl)ysteine derivatives, by inhibiting tumour growth in pre-clinical development, may contribute to the association of decreased cancer incidence with dietary glucosinolate consumption.
Current stem cell research & therapy, Mar 1, 2013
Meniscal injuries are one of the common sports injuries and their natural healing is limited. Rem... more Meniscal injuries are one of the common sports injuries and their natural healing is limited. Removal of injured meniscus alters knee biomechanics and predisposes patients to osteoarthritis. Tissue engineered meniscus provides a novel approach for the treatment of severe meniscus injury. The aim of this review is to review preclinical studies that used cell based approaches for tissue engineered meniscus. Studies were assessed for inclusion following a search in PubMed, UK PubMed central and Embase. All preclinical studies that used cell based approaches for meniscus regeneration were included in the study. Nineteen articles that used cellular approaches were reviewed. The cell types used were mesenchymal stem cells (derived from bone marrow or synovium), meniscal fibrochondrocytes, chondrocytes and bone marrow stromal cells. One study used xenogeneic bone marrow derived mesenchymal stem cells. Sixteen out of nineteen studies showed better tissue regeneration with cell based approaches when compared to acellular controls. The review included preclinical studies. The diversity of the studies made it impossible to adhere to full guidelines or perform a meta-analysis. Overall, experiments have demonstrated superior tissue integration and favourable biochemical properties of the regenerated tissues compared to acellular techniques. Few approaches however, have measured the chondroprotective ability at preclinical testing.
Injury-international Journal of The Care of The Injured, Mar 1, 2018
Meniscal injuries commonly result in osteoarthritis causing long term morbidity, lifelong treatme... more Meniscal injuries commonly result in osteoarthritis causing long term morbidity, lifelong treatment, joint replacement and significant financial burden to the Canadian healthcare system. Injuries to the outer third of the meniscus often heal well due to adequate blood supply. Healing of injuries in the inner two thirds of the meniscus are often critically retarded due to a lack of blood flow necessitating partial meniscectomy in many instances. Localized angiogenesis in the inner meniscus has yet to be achieved despite a belief that vascularization of these lesions corresponds with meniscal healing. This review briefly summarizes the growth factors that have been assessed for a role in meniscal healing and points to a significant knowledge gap in our understanding of meniscal healing.
Connective Tissue Research, Oct 3, 2011
The intracellular delivery of growth factors increases opportunities for controlling cell behavio... more The intracellular delivery of growth factors increases opportunities for controlling cell behavior and maintaining tissue homeostasis. Recently, VEGFA was reported to enhance osteogenic differentiation of mesenchymal stem cells (MSCs) through an intracrine mechanism, suggesting a new strategy to promote bone tissue formation in osteoporotic patients. The goal of this study was to design and fabricate ligand-conjugated alginate-graft-poly(ethylene glycol) microspheres for intracellular delivery and release of VEGFA in primary human MSCs to enhance osteogenic differentiation as a potential therapeutic. Three types of microspheres were synthesized and characterized by scanning electron microscopy, in vitro drug release kinetics, MSC uptake and internalization: alginate alone (Alg), alginate-graft-poly(ethylene glycol) (Algg-PEG) and alginategraft-poly(ethylene glycol)-S-S-arginine-glycine-aspartic acid (Alg-g-RGD). Each of the different microsphere formulations successfully transported bioactive VEGFA into primary human MSCs within 48 h of culture, and significantly enhanced osteogenic differentiation compared to control treatments with empty microspheres (intracellular control) or non-encapsulated VEGFA (extracellular control). Adipogenic differentiation was not affected by the presence of VEGFA intracellularly or extracellularly. These results demonstrating the internalization of alginate-based
Food and Chemical Toxicology, Apr 1, 1996
Abatraet-hlercapturic acid pathway metabolites of phenylethyl isothiocyanate inhibited the growth... more Abatraet-hlercapturic acid pathway metabolites of phenylethyl isothiocyanate inhibited the growth of human leukaemia 60 (HL60) cells in vitro. The adduct with L-cysteine, S-(N-phenylethylthiocarbamoyl)cysteine, was the most potent with strong antileukaemic activity: the median growth inhibitory concentration (GC,) value was 336 & 1 nM (N = 18) compared with GC, values of the precursor formed from dietary glucosinolates, phenylethyl isothiocyanate, 1.49 + 0.01 PM (N = 8), and the initial mercapturic acid pathway metabolite S-(N-pheny1ethylthiocarbamoyl)glutathione 5.46 f 0.36 PM (N = 18). S-(N-Benzylthiocarbamoyl)cysteine and S-(N-phenylpropylthiocarbamoyl)cysteine also had antiproliferative activipr but S-(N-phenylethylthiocarbamoyl)cysteine was the most potent compound studied. The latter induced DNA fragmentation in HL60 cells but DNA laddering characteristic of apoptosis was not observed. It had low toxicity to corresponding differentiated cells, neutrophils, in culture, and therefore the cytotoxilcity had selectivity for leukaemia cells. The antiproliferative activity of S-(N-phenylethylthiocarbamoyl)cysteine was lost during preincubation with culture medium, attributed to S-thiocarbamoyl transfer to serum proteins, which may decrease its effectiveness in viuo. The antiproliferative activity of S-(N-phenylalkylthiocarbamoyl)ysteine derivatives, by inhibiting tumour growth in pre-clinical development, may contribute to the association of decreased cancer incidence with dietary glucosinolate consumption.
Amino Acids, Jun 1, 1995
Hydroxyacyl-L-cysteine derivatives were conveniently synthesized by the reaction of the correspon... more Hydroxyacyl-L-cysteine derivatives were conveniently synthesized by the reaction of the corresponding S-(R)-2-hydroxyacylglutathione with cysteine. The (R)2-hydroxyacyl group was transferred from the S-glutathionyl moiety to S-cysteinyl, forming the corresponding (R)S-2hydroxyacylcysteine; this rearranged to the (R)N-hydroxyacylcysteine. These compounds have anti-proliferative activity associated with the inhibition of de novo pyrimidine synthesis.
Tissue Engineering Part A, 2021
To investigate the effect of soluble factors released from human nasal chondrocytes on cocultured... more To investigate the effect of soluble factors released from human nasal chondrocytes on cocultured human bone marrow mesenchymal stem cells and nasal chondrocytes tissue-engineered constructs. Cartilage engineered from pure nasal chondrocytes on a three-dimensional (3D) porous collagen scaffold was cultured indirectly in a Transwell system with cartilage engineered from a direct coculture of human bone marrow-derived mesenchymal stem cells and nasal chondrocytes on a 3D porous collagen scaffold. The soluble factors were measured in the conditioned media from the different chambers of the Transwell system. Engineered cartilage from cocultures exposed to the pure nasal chondrocyte construct exhibited reduced chondrogenic potential relative to control constructs, shown by reduced extracellular matrix deposition and increased expression of hypertrophic markers. Analysis of the soluble factors within the conditioned media showed an increase in inflammatory cytokines in the coculture chamber exposed to the pure nasal chondrocyte construct. Principal component analysis revealed that the majority of the data variance could be explained by pro-inflammatory factors and hypertrophic chondrogenesis. In conclusion, Our data suggest that inflammatory cytokines derived from nasal chondrocytes reduce the chondrogenic potential of coculture engineered cartilage through the induction of hypertrophic chondrogenesis.
Journal of Tissue Engineering
Cartilage tissue engineering aims to generate functional replacements to treat cartilage defects ... more Cartilage tissue engineering aims to generate functional replacements to treat cartilage defects from damage and osteoarthritis. Human bone marrow-derived mesenchymal stem cells (hBM-MSC) are a promising cell source for making cartilage, but current differentiation protocols require the supplementation of growth factors like TGF-β1 or −β3. This can lead to undesirable hypertrophic differentiation of hBM-MSC that progress to bone. We have found previously that exposing engineered human meniscus tissues to physiologically relevant conditions of the knee (mechanical loading and hypoxia; hence, mechano-hypoxia conditioning) increased the gene expression of hyaline cartilage markers, SOX9 and COL2A1, inhibited hypertrophic marker COL10A1, and promoted bulk mechanical property development. Adding further to this protocol, we hypothesize that combined mechano-hypoxia conditioning with TGF-β3 growth factor withdrawal will promote stable, non-hypertrophic chondrogenesis of hBM-MSC embedded i...
Journal of Tissue Engineering, 2022
The removal of skin cancer lesions on the nose often results in the loss of nasal cartilage. The ... more The removal of skin cancer lesions on the nose often results in the loss of nasal cartilage. The cartilage loss is either surgically replaced with autologous cartilage or synthetic grafts. However, these replacement options come with donor-site morbidity and resorption issues. 3-dimensional (3D) bioprinting technology offers the opportunity to engineer anatomical-shaped autologous nasal cartilage grafts. The 3D bioprinted cartilage grafts need to embody a mechanically competent extracellular matrix (ECM) to allow for surgical suturing and resistance to contraction during scar tissue formation. We investigated the effect of culture period on ECM formation and mechanical properties of 3D bioprinted constructs of human nasal chondrocytes (hNC)-laden type I collagen hydrogel in vitro and in vivo. Tissue-engineered nasal cartilage constructs developed from hNC culture in clinically approved collagen type I and type III semi-permeable membrane scaffold served as control. The resulting 3D ...
Tissue Engineering Part A, 2021
OBJECTIVE Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to form the mecha... more OBJECTIVE Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to form the mechanically responsive matrices of joint tissues including the menisci of the knee joint. The purpose of this study is to assess BMSC's potential to engineer meniscus-like tissue relative to meniscus fibrochondrocytes (MFC). METHODS MFC were isolated from castoffs of partial meniscectomy from non-osteoarthritic knees. BMSCs were developed from bone marrow aspirates of the iliac crest. All cells were of human origin. Cells were cultured in type I collagen scaffolds under normoxia (21% O2) for two weeks followed by hypoxia (3% O2) for three weeks. The structural and functional assessment of the generated meniscus constructs were based on glycosaminoglycan (GAG) content, histological appearance, gene expression, and mechanical properties. RESULTS The tissues formed by both cell types were histologically positive for Safranin-O stain and appeared more intense in the BMSC constructs. This observation was confirmed by a 2.7-fold higher GAG content. However, there was no significant difference in collagen I (COL1A2) expression in BMSC- and MFC-based constructs (p = 0.17). The expression of collagen II (COL2A1) and aggrecan (ACAN) were significantly higher in BMSCs than MFC (p≤0.05). Also, the gene expression of the hypertrophic marker collagen X (COL10A1) was 199-fold higher in BMSCs than MFC (p < 0.001). Moreover, relaxation moduli were significantly higher in BMSC-based constructs at 10%-20% strain step than MFC-based constructs. CONCLUSION BMSC-based constructs expressed higher COL2A1, ACAN, COL10A1, contained higher GAG content and exhibited higher relaxation moduli at 10-20% strain than MFC-based construct.
Frontiers in Cell and Developmental Biology, 2020
Paternal Training and Tendon Proteome transport. The present study demonstrated that the father's... more Paternal Training and Tendon Proteome transport. The present study demonstrated that the father's lifestyle could be crucial for tendon homeostasis in the first generation. Our results provide important insights into the molecular mechanisms involved in paternal intergenerational effects and potential protective outcomes of paternal RT.
Frontiers in Physiology, 2019
Cross-talk between skeletal muscle and tendon is important for tissue homeostasis. Whereas the sk... more Cross-talk between skeletal muscle and tendon is important for tissue homeostasis. Whereas the skeletal muscle response to tendon injury has been well-studied, to the best of our knowledge the tendon response to skeletal muscle injury has been neglected. Thus, we investigated calcaneal tendon extracellular matrix (ECM) remodeling after gastrocnemius muscle injury using a rat model. Wistar rats were randomly divided into four groups: control group (C; animals that were not exposed to muscle injury) and harvested at different time points post gastrocnemius muscle injury (3, 14, and 28 days) for gene expression, morphological, and biomechanical analyses. At 3 days post injury, we observed mRNA-level dysregulation of signaling pathways associated with collagen I accompanied with disrupted biomechanical properties. At 14 days post injury, we found reduced collagen content histologically accompanied by invasion of blood vessels into the tendon proper and an abundance of peritendinous sheath cells. Finally, at 28 days post injury, there were signs of recovery at the gene expression level including upregulation of transcription factors related to ECM synthesis, remodeling, and repair. At this time point, tendons also presented with increased peritendinous sheath cells, decreased adipose cells, higher Young's modulus, and lower strain to failure compared to the uninjured controls and all post injury time points. In summary, we demonstrate that the calcaneal tendon undergoes extensive ECM remodeling in response to gastrocnemius muscle injury leading to altered functional properties in a rat model. Tendon plasticity in response to skeletal muscle injury merits further investigation to understand its physiological relevance and potential clinical implications.
ACS Applied Materials & Interfaces, 2019
An ex vivo heart perfusion device preserves the donor heart in a warm beating state during transf... more An ex vivo heart perfusion device preserves the donor heart in a warm beating state during transfer between extraction and implantation surgeries. One of the current challenges includes the use of rigid and noncompliant plastic tubes, which causes injuries to the heart at the junction between the tissue and the tube. The compliant and rapidly strain-stiffening mechanical property that generates a "J-shaped" stress-strain behavior is necessary for producing the Windkessel effect, which ensures continuous flow of blood through the aorta. In this study, we mimic the J-shaped and anisotropic stressstrain behavior of human aorta in synthetic elastomers to replace the problematic noncompliant plastic tube. First, we assess the mechanical properties of human (n = 1) and porcine aorta (n = 14) to quantify the nonlinear and anisotropic behavior under uniaxial tensile stress from five different regions of the aorta. Second, fabric-reinforced elastomer composites were prepared by reinforcing silicone elastomers with embedded fabrics in a trilayer geometry. The knitted structures of the fabric provide strain-stiffening as well as anisotropic mechanical properties of the resulting composite in a deterministic manner. By optimizing the combination between different elastomers and fabrics, the resulting composites matched the J-shaped and anisotropic stress-strain behavior of natural human and porcine aorta. Finally, improved analytical constitutive models based on Gent's and Mooney-Rivlin's constitutive model (to describe the elastomer matrix) combined with Holzapfel-Gasser-Ogden's model (to represent the stiffer fabrics) were developed to describe the J-shaped behavior of the natural aortas and the fabric-reinforced composites. We anticipate that the suggested fabric-reinforced silicone elastomer composite design concept can be used to develop complex soft biomaterials, as well as in emerging engineering fields such as soft robotics and microfluidics, where the Windkessel effect can be useful in regulating the flow of fluids.
Journal of Pediatric Urology, 2019
Partial bladder outlet obstruction (pBOO) is characterized by an initial inflammatory response th... more Partial bladder outlet obstruction (pBOO) is characterized by an initial inflammatory response that progresses to smooth muscle hypertrophy and fibrosis. Current treatment modalities carry high risk of morbidity. Mesenchymal stem cells (MSCs) are undifferentiated adult cells with reparative, immunomodulatory, and anti-inflammatory capacities. The ability of MSCs to inhibit inflammatory and profibrotic pathways in bladder cells has been recently reported. This study aimed to investigate the therapeutic effects of MSCs on pBOO-induced inflammatory, profibrotic signaling pathways and end-organ physiology.
Acta Biomaterialia, 2018
The objective of this study was to investigate whether meniscus-derived decellularized matrix (DC... more The objective of this study was to investigate whether meniscus-derived decellularized matrix (DCM) has the capacity to induce differentiation of synovial fluid-derived mesenchymal stem cells (SF-MSCs) towards a meniscus fibrochondrocyte (MFC) phenotype. The potential roles of transforming growth factor beta-3 (TGF-β 3) and insulin-like growth factor 1 (IGF-1) in the differentiation of SF-MSCs towards an MFC phenotype were also investigated. SF-MSCs were isolated via plastic adherence cell culture from the synovial fluid of five donors (5 male, average age 34.4 years). Porous DCM was generated by homogenizing and freeze-drying fresh normal human cadaveric meniscus tissue. SF-MSCs were seeded and cultured on the DCM scaffold in a defined serum-free media (SFM) supplemented with or without the combination of TGF-β 3 and IGF-1. Cell pellets of SF-MSCs were cultured in SFM with either TGF-β 3 or IGF-1 or their combination as controls. The duration of culture was 3 weeks for both experimental configurations. We assessed newly-formed tissues by biochemical assays, scanning electron microscopy (SEM), immunofluorescence and quantitative real-time PCR (qPCR). The combination of TGF-β 3 and IGF1 induced production of the cartilaginous matrix in DCM and upregulated the expression of aggrecan, collagens I and II. Moreover, the SF-MSCs exhibited a round morphology in the DCM scaffolds in the presence of the growth factors. In pellets, combined IGF-1 and TGF-β 3 synergistically enhanced cartilaginous matrix production. In contrast to bone marrow mesenchymal stem cells (BM-MSCs), the differentiated SF-MSCs showed little evidence of the expression of the hypertrophic differentiation marker, collagen X. In conclusion, meniscus-derived DCM appears to require exogenous growth factor supplementation to direct differentiation of SF-MSCs.
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Papers by Adetola Adesida