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Biomedical subjects

Jennifer H Elisseeff

Publications and source records attributed to Jennifer H Elisseeff.

At least 19 recordsLinked to original sources
PubMed2026

Senotypes define the diverse landscape of senescent cells.

Cellular senescence was initially defined in vitro as a stable cell-cycle arrest that occurs after repeated replication, but it is now recognized as a heterogeneous state shaped by cell type, species, senescence-inducing stress, tissue microenvironment and time. To organize this complexity, we propose the term 'senotype' to classify senescent cells by their inputs, molecular features and functional effects. We outline a practical framework incorporating: (1) cell identity and context; (2) inducing mechanism; (3) temporal stage; (4) multimodal molecular and structural features; and (5) physiological or pathological functions. Experimentally defined senotypes can serve as references for interpreting tissue-derived senotypes, where parameters may be incomplete. Senotypes should be anchored in combinations of core hallmarks (that is, durable cell-cycle arrest, altered secretory profiles, macromolecular or organelle damage, disrupted homeostasis) rather than single markers. Advances in single-cell, spatial, proteomic and computational methods enable rigorous senotype characterization, improving consistency and accelerating development of targeted senotherapeutics.

Cellular Senescence↗
PubMed2026

Differential cell signaling testing for cell-cell communication inference from single-cell data by dominoSignal.

MOTIVATION: Algorithms for ligand-receptor network inference have emerged as commonly used tools to estimate cell-cell communication from reference single-cell data. Many studies employ these algorithms to compare signaling between conditions and lack methods to statistically identify signals that are significantly different. We previously developed the cell communication inference algorithm Domino, which considers ligand and receptor gene expression in association with downstream transcription factor activity scoring. We developed the dominoSignal software to innovate upon Domino and extend its functionality to test statistically differential cellular signaling. RESULTS: This new functionality includes the compilation of active signals as linkages from multiple subjects in a single-cell data set and testing condition-dependent signaling linkage. The software is applicable for analysis of single-cell data sets with multiple subjects as biological replicates as well as with bootstrapped replicates from data sets with few or pooled subjects. We use simulation studies to benchmark the number of subjects in compared groups and cells within an annotated cell type sufficient to accurately identify differential linkages. We demonstrate the application of the Differential Cell Signaling Test (DCST) in the dominoSignal software to investigate consequences of cancer cell phenotypes and immunotherapy on cell-cell communication in tumor microenvironments. These applications in cancer studies demonstrate the ability of differential cell signaling analysis to infer changes to cell communication networks from therapeutic or experimental perturbations, which is broadly applicable across biological systems. AVAILABILITY: dominoSignal is available through Bioconductor at https://www.bioconductor.org/packages/release/bioc/html/dominoSignal.html.

Cell Communication↗
PubMed2006

Reorganization of actin filaments enhances chondrogenic differentiation of cells derived from murine embryonic stem cells.

Differentiation of embryonic stem cells is of great interest to developmental biology and regenerative medicine. This study investigated the effects of cytochalasin D (CD) on the distribution of actin filaments in mouse embryoid body (EB)-derived cells. Furthermore, CD was applied to chondrogenic medium to examine its chondrogenic effect. CD at a concentration of 1 microg/ml disrupted stress fibers in EB-derived cells. Actin filaments in treated cells reorganized into a peripheral pattern, and type II collagen was detected by immunocytochemistry. The expression of type II collagen, Sox9, and at a later time point, aggrecan was up-regulated after CD treatment. In the CD-treated cells, Oct4 and Sox2, representing undifferentiation, were down-regulated as well as Sox1, AFP, and CTN-1, representing ectoderm, endoderm, and cardiogenesis, respectively. In conclusion, CD treatment enhances chondrogenesis of EB-derived cells. Moreover, it promotes a more complete stem cell differentiation toward chondrogenesis, when cultured in chondrogenic medium.

Actin Cytoskeleton↗
PubMed2006

Collagen mimetic peptide-conjugated photopolymerizable PEG hydrogel.

Collagen mimetic peptide (CMP) with a specific amino acid sequence, -(Pro-Hyp-Gly)(x)-, forms a triple helix conformation that resembles the native protein structure of natural collagens. CMP previously has been shown to associate with type I collagen molecules and fibers via a strand invasion process. We hypothesized that when poly(ethylene glycol) (PEG) hydrogel, a non-adhesive tissue engineering scaffold, is conjugated with CMP, it may retain cell-secreted collagens and also form physical crosslinks that can be manipulated by cells. A photopolymerizable CMP derivative was synthesized and copolymerized with poly(ethylene oxide) diacrylate to create a novel PEG hydrogel. In a model retention experiment, diffusional loss of type I collagen that was added to the hydrogel was limited. Chondrocytes were encapsulated in the hydrogel to examine its use as a tissue engineering scaffold. After 2 weeks, the biochemical analysis of the CMP-conjugated PEG gel revealed an 87% increase in glycosaminoglycan content and a 103% increase in collagen content compared to that of control PEG hydrogels. The histology and immunohistochemistry analyses also showed increased staining of extracellular matrix. These results indicate that the CMP enhances the tissue production of cells encapsulated in the PEG hydrogel by providing cell-manipulated crosslinks and collagen binding sites that simulate natural extracellular matrix.

Animals↗
PubMed2006

Metabolic changes in mesenchymal stem cells in osteogenic medium measured by autofluorescence spectroscopy.

The purpose of this study was to measure metabolic changes in mesenchymal stem cells (MSCs) placed in osteogenic medium by autofluorescence spectroscopy. MSCs were plated in stem cell-supporting or osteogenic medium and imaged. Shift from the basic growth environment to the inductive osteogenic environment was confirmed by reverse transcription-polymerase chain reaction. Reduced pyridine nucleotides were detected by exciting near 366 nm and measuring fluorescence at 450 nm, and oxidized flavoproteins were detected by exciting at 460 nm and measuring fluorescence at 540 nm. The ratio of these fluorescence measurements, reduction-oxidation (redox) fluorometry, is a noninvasive measure of the cellular metabolic state. The detected pyridine nucleotide to flavoprotein ratio decreased upon transitioning from the stem cell to the differentiated state, as well as with increasing cell density and cell-cell contact. MSC metabolism increased upon placement in differentiating medium and with increasing cell density and contact. Redox fluorometry is a feasible, noninvasive technique for distinguishing MSCs from further differentiated cells.

Animals↗
PubMed2006

Modified microkeratome-assisted posterior lamellar keratoplasty using a tissue adhesive.

OBJECTIVE: To compare graft stability and astigmatic change using suture vs tissue adhesive in an experimental model of microkeratome-assisted posterior lamellar keratoplasty. METHODS: A 300-microm-thick partial flap keratectomy was performed in human donor corneoscleral rims using an artificial anterior chamber and a manual microkeratome. The flap stopped at the left central opening border, providing a wide hinge to add stability. After flap reflection, a 6.25-mm trephination was performed to obtain a disc of posterior stroma, Descemet membrane, and endothelium. The disc was positioned in a sutureless fashion, and the flap secured with either 5 interrupted sutures or a chondroitin-sulfate-aldehyde-based adhesive. Increasing intrachamber pressures were created to detect graft stability. Videokeratographic data were recorded to evaluate astigmatic change. RESULTS: The mean (SD) astigmatic change was 3.08 (0.84) diopters (D) in the sutured group and 1.13 (0.55) D in the glued group (P = .008). Mean (SD) resisted pressures were 95.68 (27.38) mm Hg and 82.45 (18.40) mm Hg in the sutured and glued groups, respectively (P = .97). CONCLUSION: This modified technique of microkeratome-assisted posterior lamellar keratoplasty showed excellent graft stability in both groups. Flaps sealed with the novel tissue adhesive had reduced astigmatic changes in our experimental model. CLINICAL RELEVANCE: Sutureless microkeratome-assisted posterior lamellar keratoplasty using tissue adhesive may become a new alternative in the surgical treatment of corneal endothelial disorders.

Aged↗
PubMed2006

An analysis of the integration between articular cartilage and nondegradable hydrogel using magnetic resonance imaging.

A hydrogel is a highly hydrated polymer gel suitable for use as a scaffold for tissue engineering. One important application is to the repair of cartilage defects due to injury or osteoarthritis. Integration of the hydrogel with surrounding tissue is critical for the long-term functionality of the implant; however direct visualization of integration is difficult and invasive. Accordingly, we used MRI to noninvasively investigate the integration of hydrogel in cartilage. Two integration methods were assessed: (1) cartilage-initiated and (2) chemical, using chondroitin sulphate-methacrylate-aldehyde (CS-MA-ald) as an adhesive. These were compared to a control group, that is, standard, nonintegrated hydrogel photopolymerization. Spatial variation of the transverse relaxation time, T(2), across the transition region was used to determine the effectiveness of integration. In the CS-MA-ald group only, two interfaces were found. This provides evidence of an intermediate adhesive layer between hydrogel and cartilage. Second, the thickness of the transition region between hydrogel to cartilage in the CS-MA-ald group was 1.32 mm as compared to 1.20 mm and 1.17 mm in the tissue-initiated and nonintegrated groups, respectively. We interpret this as a more gradual transition region of hydrogel to cartilage and hence a greater degree of integration when an adhesive layer is present.

Animals↗
PubMed2005

Biodegradable and photocrosslinkable polyphosphoester hydrogel.

A new biodegradable, photocrosslinkable and multifunctional macromer, poly(6-aminohexyl propylene phosphate) (PPE-HA)-ACRL, was synthesized by conjugation of acrylate groups to the side chains of PPE-HA. By controlling the synthetic conditions, different weight fractions of acrylate in the macromers were achieved as confirmed by 1H NMR. The hydrogels obtained from PPE-HA-ACRL through photocrosslinking were dominantly elastic. With increasing acrylate contents in the macromers, the hydrogels exhibited a lower swelling ratio and higher mechanical strength. The hydrogels with different crosslinking densities lost between 4.3% and 37.4% of their mass in 84 days when incubated in phosphate-buffered saline at 37 degrees C. No significant cytotoxicity of the macromers against bone marrow-derived mesenchymal stem cells from goat (GMSC) was observed at a concentration up to 10mg/ml. Finally, GMSCs encapsulated in the photopolymerized gel maintained their viability when cultured in osteogenic medium for three weeks. Clear mineralization in the hydrogel scaffold was revealed by Von Kossa staining. This study suggests the potential of these biodegradable and photocrosslinkable as injectable tissue engineering scaffolds.

Absorbable Implants↗
PubMed2005

Variable cytocompatibility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation.

The development of biocompatible photopolymerizing polymers for biomedical and tissue engineering applications has the potential to reduce the invasiveness and cost of biomaterial implants designed to repair or augment tissues. However, more information is needed about the cellular toxicity of the compounds and initiators used in these systems. The current study evaluates the cellular toxicity of three ultraviolet sensitive photoinitiators on six different cell populations that are used for engineering numerous tissues. The photoinitiator 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Irgacure 2959) caused minimal toxicity (cell death) over a broad range of mammalian cell types and species. It was also demonstrated that different cell types have variable responses to identical concentrations of the same photoinitiator. While inherent differences in the cell lines may contribute to the variable cytotoxicity, a correlation between cellular proliferation rate (population doubling time) and increased cytotoxicity of the photoinitiator was observed. Cell lines that divided more quickly were more sensitive to photoinitiator-induced cell death. In summary, the photoinitiator Irgacure 2959 is well tolerated by many cell types over a range of mammalian species. Cell photoencapsulation strategies may be optimized to improve cell survival by manipulating proliferation rate.

Biocompatible Materials↗
PubMed2005

Improving long-term projection in nipple reconstruction using human acellular dermal matrix: an animal model.

Reconstructed nipples rapidly lose projection. We describe the use of human acellular dermal matrix (ADM) to improve long-term projection of nipple flaps. Athymic rats were randomized to 3 groups; each received 2 nipples: bell flap (control, n = 16 nipples), bell flap with a cylinder of implanted ADM (n = 24), or bell flap with intraflap injection of micronized ADM (MADM) (n = 10). Seven of 24 ADM nipples extruded (30%). By 12 weeks, the control nipples maintained 44% of initial projection compared with 70% for ADM nipples (P = 0.000025). The MADM nipples maintained 49% of initial projection after 12 weeks (P = 0.55 compared with control). No MADM nipples extruded. ADM grafts maintain long-term projection better than local tissue flaps alone. We hypothesize that MADM may limit extrusion and allow for serial injection of nipples. Based on the promising results of this study, clinical trials are warranted using human ADM and/or human MADM for nipple reconstruction.

Animals↗
PubMed2005

A modified chondroitin sulfate aldehyde adhesive for sealing corneal incisions.

PURPOSE: To compare a modified chondroitin sulfate aldehyde adhesive with standard sutures for sealing corneal incisions. METHODS: A keratome knife was used to create non-self-sealing, uniplanar, 3-mm, clear corneal incisions in enucleated rabbit eyes (n = 18). The wounds were sealed with either a chondroitin sulfate-aldehyde adhesive (n = 8), three 10-0 nylon sutures (n = 5), or one 10-0 nylon suture (n = 5). Wound stability was tested by filling the globes with balanced salt solution through an anterior chamber port and slowly increasing the IOP. The pressure changes were monitored with a digital manometer connected to the anterior chamber, and leak pressure was recorded for each eye. Confocal microscopy was performed on the glued eyes, to document the glue distribution along the wound. RESULTS: The mean leak pressures in the single-suture and three-suture subgroups were 26.4 +/- 6.0 and 44.3 +/- 8.2 mm Hg (SD), respectively. The maximum IOP achieved in eyes that received the glue was 104.7 mm Hg with a mean of 101.4 +/- 3.2 mm Hg. None of the eyes in which glue was used showed leakage. At confocal microscopy, the glue was distributed inside the wound edges as a homogeneous thin layer of a less dense signal than that of the stroma. CONCLUSIONS: A novel chondroitin sulfate-aldehyde adhesive was shown to be effective ex vivo for sealing corneal incisions in rabbit eyes and was superior to sutures for this purpose.

Aldehydes↗
PubMed2004

Photocrosslinkable polysaccharides based on chondroitin sulfate.

Photopolymerizing hydrogels have demonstrated potential for use as a scaffold in numerous tissue-engineering applications. The majority of photopolymerizing hydrogels are made from purely synthetic polymers. The purpose of this study was to synthesize and characterize photopolymerizing hydrogels derived from the biopolymer chondroitin sulfate in order to enhance the bioactivity of the scaffold and potentially improve tissue regeneration. Methacrylate groups were added to chondroitin sulfate, a major component of cartilage, using glycidyl methacrylate. The gels exhibited viscoelastic behavior typical of hydrogels. Cogels based on chondroitin sulfate and poly(ethylene glycol) demonstrated increasing pore size with increasing concentration of chondroitin sulfate as determined by water content, mechanical strength, and morphology using scanning electron microscopy. The chondroitin sulfate hydrogels degraded specifically in the presence of the enzyme chondroitinase. Chondrocytes remained viable after photoencapsulation and incubation in the biogels, suggesting their possible use for cartilage tissue engineering.

Animals↗
PubMed2004

Engineering structurally organized cartilage and bone tissues.

The field of tissue engineering promises to deliver biological substitutes to repair or replace tissues in the body that have been injured or diseased. The clinical demand for musculoskeletal tissues is particularly high, especially for cartilage and bone defects. Although they are generally considered biologically simple structures, musculoskeletal tissues consist of highly organized three-dimensional networks of cells and matrix, giving rise to tissue structures with remarkable mechanical properties. Although the field of cartilage and bone tissue engineering has progressed significantly in recent years, the development of structurally ordered tissues has not been accomplished. More strategies are needed to ensure that the appropriate cell and matrix organization is being achieved in the engineered tissues. This review emphasizes how different cell types and scaffold designs can be used to modulate tissue properties and engineer more complex tissue structures, with emphasis on cartilage and bone tissues.

Animals↗
PubMed2004

Adult stem cell driven genesis of human-shaped articular condyle.

Uniform design of synovial articulations across mammalian species is challenged by their common susceptibility to joint degeneration. The present study was designed to investigate the possibility of creating human-shaped articular condyles by rat bone marrow-derived mesenchymal stem cells (MSCs) encapsulated in a biocompatible poly(ethylene glycol)-based hydrogel. Rat MSCs were harvested, expanded in culture, and treated with either chondrogenic or osteogenic supplements. Rat MSC-derived chondrogenic and osteogenic cells were loaded in hydrogel suspensions in two stratified and yet integrated hydrogel layers that were sequentially photopolymerized in a human condylar mold. Harvested articular condyles from 4-week in vivo implantation demonstrated stratified layers of chondrogenesis and osteogenesis. Parallel in vitro experiments using goat and rat MSCs corroborated in vivo data by demonstrating the expression of chondrogenic and osteogenic markers by biochemical and mRNA analyses. Ex vivo incubated goat MSC-derived chondral constructs contained cartilage-related glycosaminoglycans and collagen. By contrast, goat MSC-derived osteogenic constructs expressed alkaline phosphatase and osteonectin genes, and showed escalating calcium content over time. Rat MSC-derived osteogenic constructs were stiffer than rat MSC-derived chondrogenic constructs upon nanoindentation with atomic force microscopy. These findings may serve as a primitive proof of concept for ultimate tissue-engineered replacement of degenerated articular condyles via a single population of adult mesenchymal stem cells.

Animals↗
PubMed2003

Novel human endothelial cell-engineered polyurethane biomaterials for cardiovascular biomedical applications.

A tri-block coupling-polymer composed of 4,4'-methylenediphenyl diisocyanate and poly (ethylene oxide) (PEO), abbreviated MPEO, was used as the template surface-modifying additive (SMA), based on which selected amino acids (lysine, arginine, glycin, and aspartic acid) and RGD peptide were respectively conjugated as functional endgroups of the PEO spacer-arms through sulfonyl chloride-activation routes. After the immobilization of biofunctional factors, the SMA-MPEO derivatives were noncovalently introduced onto the biomedical poly(ether urethane) (PEU) surfaces by physical blending methods. The SMA synthesis and PEU surface modification were monitored and analyzed by nuclear magnetic resonance spectroscopy, attenuated total reflection-infrared spectroscopy, and X-ray photoelectron spectroscopy. The human umbilical vein endothelial cells (HUVECs) were collected and harvested manually by collagenase digestion. The cell culture was performed respectively on the MPEO derivative-modified PEU surfaces and also on the surfaces of the commercially available polystyrene cell-culture plates (TCPS) for control. The cell adhesion rates and cell proliferation rates of the in vitro cultivated HUVEC were measured using flow cytometry. The individual cell viability rates were determined with MTT assay. The cell morphologies of the living HUVECs were investigated by optical inverted microscopy, and more detailed information was acquired from scanning electrical microscopy. The results indicated that the efficacy of SMA functional endgroups was the dominant factor for HUVEC compatibility; the proper-sized PEO spacers (M(w) 2 k) could support and mobilize the functional endgroups, optimizing the surface (interface) environment for the cell growth. As the endgroups of the SMA-MPEO derivatives and the bio-functional factors, the basic amino acids (lysine and arginine) demonstrated similar performances to that of the widely acknowledged cell growth-promoter, RGD peptide, which were superior to TCPS. Therefore, these MPEO derivative-modified PEU materials are promising to serve as novel polymeric permanent implants or interventional devices for cardiovascular biomedical applications.

Biocompatible Materials↗
PubMed2003

Synthesis and characterization of a novel degradable phosphate-containing hydrogel.

A phosphate-containing and photocrosslinkable polymer, poly(ethylene glycol) di-[ethyl phosphatidyl (ethylene glycol) methacrylate], "PhosPEG-dMA", was synthesized. As a water-soluble macromer, PhosPEG-dMA is suitable for in situ injection and cell-encapsulation by light-induced gelation to produce a novel biocompatible and biodegradable hydrogel for application to cartilage and bone tissue engineering. 1H-NMR, MALDI-TOF mass spectrometry, and elemental analysis were performed to characterize the macromer. Fifteen and 20% (w/v) PhosPEG gels were photopolymerized using UV light with 0.05% photoinitiator. The swelling and water content of the hydrogels was studied and the crosslinking efficiency (density) of the macromers was simulated based on the Peppas-Merrill model. Torsional mechanical analysis of the gels demonstrated a viscoelastic characteristic with high elasticity. The results indicated that, with the fixed PEG-segment size, the greater strength and water-content of the gels depend on the higher crosslinking density. Degradation experiments revealed a linear dry-weight loss of 22.88% and 16.08% from 15% and 20% PhosPEG gels after 9 weeks. The 31P-NMR detected the signals of both phosphate and phosphoric acid in the degrading systems (the gel bulks and the supernatants). Finally, human mesenchymal stem cells (hMSC) were encapsulated into PhosPEG Gel constructs and remained viable as qualitatively demonstrated by "Live/Dead" cell staining assay and MTT assay. The cell-encapsulation efficiency was determined by the characterization of DNA content in each gel construct and the semi-quantitative analysis of the cell viability was also performed by the DNA assay combined with MTT assay.

Acrylates↗
PubMed2002

In situ forming degradable networks and their application in tissue engineering and drug delivery.

Multifunctional macromers based on poly(ethylene glycol) and poly(vinyl alcohol) were photopolymerized to form degradable hydrogel networks. The degradation behavior of the highly swollen gels was characterized by monitoring changes in their mass loss, degree of swelling, and compressive modulus. Experimental results show that the modulus decreases exponentially with time, while the volumetric swelling ratio increases exponentially. A degradation mechanism assuming pseudo first-order hydrolysis kinetics and accounting for the structure of the crosslinked networks successfully predicted the experimentally observed trends in these properties with degradation. Once verified, the proposed degradation mechanism was extended to correlate network degradation kinetics, and subsequent changes in network structure, with release behavior of bioactive molecules from these dynamic systems. A theoretical model utilizing a statistical approach to predict the cleavage of crosslinks within the network was used to predict the complex erosion profiles produced by these hydrogels. Finally, the application of these macromers as in situ forming hydrogel constructs for cartilage tissue engineering is demonstrated.

Animals↗