Petter Angell Olsen

• Martinez, Mikel Amirola; Combriat, Thomas Michel Daniel; Ferencevic, Katharina; Wilhelmsen, Ingrid; Dalmao-Fernandez, Andrea & Olsen, Petter Angell [Show all 9 contributors for this article] (2025). Aspects of zone-like identity and holotomographic tracking of human stem cell-derived liver sinusoidal endothelial cells. Frontiers in Cell and Developmental Biology. 13. doi: 10.3389/fcell.2025.1528991. Full text in Research Archive Show summary

  Introduction: Liver sinusoidal endothelial cells (LSEC) are specialized endothelial cells with unique metabolic and barrier functions adapted to the needs of the liver sinusoid. LSECs are highly sensitive to their environment, and this fragile nature causes challenges in analyzing their phenotype under in vitro conditions. Methods: In this work, we first differentiated LSEC-like cells (scLSECs) from two human pluripotent stem cell lines and characterized them by a panel of qPCR markers, immunohistochemistry, substrate oxidation for energy metabolism, scavenger function, and nitric oxide secretion. We then introduced holotomography, a technique that allows to recover quantitative and three-dimensional information about the refractive indexes of cell components, as a tool to image and track scLSEC in vitro in a minimally intrusive, label-free manner. Results and discussion: Holotomography and developed machine learning-based algorithm for image processing allowed us to describe and monitor changes in intracellular pore-like structures over time. Finally, we tested the possibility of inducing aspects of zone-specific LSEC phenotype and metabolism using culture-based treatments, which resulted in modest shifts in marker expression and metabolic activity. The presented strategy provides an advanced tool kit for investigating liver endothelial cells.

• Wilhelmsen, Ingrid; Combriat, Thomas Michel Daniel; Dalmao-Fernandez, Andrea; Stokowiec, Justyna; Wang, Chencheng & Olsen, Petter Angell [Show all 10 contributors for this article] (2024). The effects of TGF-β-induced activation and starvation of vitamin A and palmitic acid on human stem cell-derived hepatic stellate cells. Stem Cell Research & Therapy. 15(223). doi: 10.1186/s13287-024-03852-8. Full text in Research Archive Show summary

  Background Hepatic stellate cells (HSC) have numerous critical roles in liver function and homeostasis, while they are also known for their importance during liver injury and fibrosis. There is therefore a need for relevant in vitro human HSC models to fill current knowledge gaps. In particular, the roles of vitamin A (VA), lipid droplets (LDs), and energy metabolism in human HSC activation are poorly understood. Methods In this study, human pluripotent stem cell-derived HSCs (scHSCs), benchmarked to human primary HSC, were exposed to 48-hour starvation of retinol (ROL) and palmitic acid (PA) in the presence or absence of the potent HSC activator TGF-β. The interventions were studied by an extensive set of phenotypic and functional analyses, including transcriptomic analysis, measurement of activation-related proteins and cytokines, VA- and LD storage, and cell energy metabolism. Results The results show that though the starvation of ROL and PA alone did not induce scHSC activation, the starvation amplified the TGF-β-induced activation-related transcriptome. However, TGF-β-induced activation alone did not lead to a reduction in VA or LD stores. Additionally, reduced glycolysis and increased mitochondrial fission were observed in response to TGF-β. Conclusions scHSCs are robust models for activation studies. The loss of VA and LDs is not sufficient for scHSC activation in vitro, but may amplify the TGF-β-induced activation response. Collectively, our work provides an extensive framework for studying human HSCs in healthy and diseased conditions.

• Combriat, Thomas Michel Daniel; Olsen, Petter Angell; Låstad, Silja Borring; Malthe-Sørenssen, Anders; Krauss, Stefan Johannes Karl & Dysthe, Dag Kristian (2024). Acoustic Wave-Induced Stroboscopic Optical Mechanotyping of Adherent Cells. Advanced Science. 11(16). doi: 10.1002/advs.202307929. Full text in Research Archive Show summary

  In this study, a novel, high content technique using a cylindrical acoustic transducer, stroboscopic fast imaging, and homodyne detection to recover the mechanical properties (dynamic shear modulus) of living adherent cells at low ultrasonic frequencies is presented. By analyzing the micro-oscillations of cells, whole populations are simultaneously mechanotyped with sub-cellular resolution. The technique can be combined with standard fluorescence imaging allowing to further cross-correlate biological and mechanical information. The potential of the technique is demonstrated by mechanotyping co-cultures of different cell types with significantly different mechanical properties.

• Wang, Chencheng; Abadpour, Shadab; Aizenshtadt, Aleksandra; Dalmao-Fernandez, Andrea; Høyem, Merete & Wilhelmsen, Ingrid [Show all 13 contributors for this article] (2024). Cell identity dynamics and insight into insulin secretagogues when employing stem cell-derived islets for disease modeling. Frontiers in Bioengineering and Biotechnology. 12. doi: 10.3389/fbioe.2024.1392575. Full text in Research Archive Show summary

  Stem cell-derived islets (SC-islets) are not only an unlimited source for cell-based therapy of type 1 diabetes but have also emerged as an attractive material for modeling diabetes and conducting screening for treatment options. Prior to SC-islets becoming the established standard for disease modeling and drug development, it is essential to understand their response to various nutrient sources in vitro. This study demonstrates an enhanced efficiency of pancreatic endocrine cell differentiation through the incorporation of WNT signaling inhibition following the definitive endoderm stage. We have identified a tri-hormonal cell population within SC-islets, which undergoes reduction concurrent with the emergence of elevated numbers of glucagon-positive cells during extended in vitro culture. Over a 6-week period of in vitro culture, the SC-islets consistently demonstrated robust insulin secretion in response to glucose stimulation. Moreover, they manifested diverse reactivity patterns when exposed to distinct nutrient sources and exhibited deviant glycolytic metabolic characteristics in comparison to human primary islets. Although the SC-islets demonstrated an aberrant glucose metabolism trafficking, the evaluation of a potential antidiabetic drug, pyruvate kinase agonist known as TEPP46, significantly improved in vitro insulin secretion of SC-islets. Overall, this study provided cell identity dynamics investigation of SC-islets during prolonged culturing in vitro, and insights into insulin secretagogues. Associated advantages and limitations were discussed when employing SC-islets for disease modeling.

• Wang, Chencheng; Abadpour, Shadab; Olsen, Petter Angell; Wang, Daxin; Stokowiec, Justyna & Chera, Simona [Show all 11 contributors for this article] (2024). Glucose Concentration in Regulating Induced Pluripotent Stem Cells Differentiation Toward Insulin-Producing Cells. Transplant International. ISSN 0934-0874. 37. doi: 10.3389/ti.2024.11900. Full text in Research Archive Show summary

  The generation of insulin-producing cells from human-induced pluripotent stem cells holds great potential for diabetes modeling and treatment. However, existing protocols typically involve incubating cells with un-physiologically high concentrations of glucose, which often fail to generate fully functional IPCs. Here, we investigated the influence of high (20 mM) versus low (5.5 mM) glucose concentrations on IPCs differentiation in three hiPSC lines. In two hiPSC lines that were unable to differentiate to IPCs sufficiently, we found that high glucose during differentiation leads to a shortage of NKX6.1+ cells that have co-expression with PDX1 due to insufficient NKX6.1 gene activation, thus further reducing differentiation efficiency. Furthermore, high glucose during differentiation weakened mitochondrial respiration ability. In the third iPSC line, which is IPC differentiation amenable, glucose concentrations did not affect the PDX1/NKX6.1 expression and differentiation efficiency. In addition, glucose-stimulated insulin secretion was only seen in the differentiation under a high glucose condition. These IPCs have higher KATP channel activity and were linked to sufficient ABCC8 gene expression under a high glucose condition. These data suggest high glucose concentration during IPC differentiation is necessary to generate functional IPCs. However, in cell lines that were IPC differentiation unamenable, high glucose could worsen the situation.

• Kwak, Dongho; Combriat, Thomas Michel Daniel; Jensenius, Alexander Refsum & Olsen, Petter Angell (2023). Characterization of Mechanical and Cellular Effects of Rhythmic Vertical Vibrations on Adherent Cell Cultures. Bioengineering. 10(7), p. 1–19. doi: 10.3390/bioengineering10070811. Full text in Research Archive Show summary

  This paper presents an innovative experimental setup that employs the principles of audio technology to subject adherent cells to rhythmic vertical vibrations. We employ a novel approach that combines three-axis acceleration measurements and particle tracking velocimetry to evaluate the setup’s performance. This allows us to estimate crucial parameters such as root mean square acceleration, fluid flow patterns, and shear stress generated within the cell culture wells when subjected to various vibration types. The experimental conditions consisted of four vibrational modes: No Vibration, Continuous Vibration, Regular Pulse, and Variable Pulse. To evaluate the effects on cells, we utilized fluorescence microscopy and a customized feature extraction algorithm to analyze the F-actin filament structures. Our findings indicate a consistent trend across all vibrated cell cultures, revealing a reduction in size and altered orientation (2D angle) of the filaments. Furthermore, we observed cell accumulations in the G1 cell cycle phase in cells treated with Continuous Vibration and Regular Pulse. Our results demonstrate a negative correlation between the magnitude of mechanical stimuli and the size of F-actin filaments, as well as a positive correlation with the accumulations of cells in the G1 phase of the cell cycle. By unraveling these analyses, this study paves the way for future investigations and provides a compelling framework for comprehending the intricate cellular responses to rhythmic mechanical stimulation.

• Brinch, Shoshy Alam; Amundsen-Isaksen, Enya; Espada, Sandra; Hammarström, Clara Louise; Aizenshtadt, Aleksandra & Olsen, Petter Angell [Show all 18 contributors for this article] (2022). The Tankyrase Inhibitor OM-153 Demonstrates Antitumor Efficacy and a Therapeutic Window in Mouse Models. Cancer Research Communications. 2(4), p. 233–245. doi: 10.1158/2767-9764.CRC-22-0027. Full text in Research Archive
• Kwak, Dongho; Olsen, Petter Angell; Danielsen, Anne & Jensenius, Alexander Refsum (2022). A trio of biological rhythms and their relevance in rhythmic mechanical stimulation of cell cultures. Frontiers in Psychology. 13. doi: 10.3389/fpsyg.2022.867191. Full text in Research Archive Show summary

  The primary aim of this article is to provide a biological rhythm model based on previous theoretical and experimental findings to promote more comprehensive studies of rhythmic mechanical stimulation of cell cultures, which relates to tissue engineering and regenerative medicine fields. Through an interdisciplinary approach where different standpoints from biology and musicology are combined, we explore some of the core rhythmic features of biological and cellular rhythmic processes and present them as a trio model that aims to afford a basic but fundamental understanding of the connections between various biological rhythms. It is vital to highlight such links since rhythmic mechanical stimulation and its effect on cell cultures are vastly underexplored even though the cellular response to mechanical stimuli (mechanotransduction) has been studied widely and relevant experimental evidence suggests mechanotransduction processes are rhythmic.

• Olsen, Petter Angell & Krauss, Stefan Johannes Karl (2021). The Adenoviral E1B-55k Protein Present in HEK293 Cells Mediates Abnormal Accumulation of Key WNT Signaling Proteins in Large Cytoplasmic Aggregates. Genes. 12(12). doi: 10.3390/genes12121920. Full text in Research Archive Show summary

  HEK293 cells are one of the most widely used cell lines in research, and HEK293 cells are frequently used as an in vitro model for studying the WNT signaling pathway. The HEK293 cell line was originally established by transfection of human embryonic kidney cells with sheared adenovirus 5 DNA, and it is known that that HEK293 cells stably express the adenoviral E1A and E1B-55k proteins. Here, we show that HEK293 cells display an unexpected distribution of key components of the WNT/β-catenin signaling pathway where AXIN1, APC, DVL2 and tankyrase are all co-localized in large spherical cytoplasmic aggregates. The cytoplasmic aggregates are enclosed by a narrow layer of the adenoviral E1B-55k protein. The reduction of E1B-55k protein levels leads to the disappearance of the cytoplasmic aggregates thus corroborating an essential role of the E1B-55k protein in mediating the formation of the aggregates. Furthermore, HEK293 cells with reduced E1B-55k protein levels display reduced levels of transcriptional activation of WNT/β-catenin signaling upon stimulation by the Wnt3A agonist. The demonstrated influence of the E1B-55k protein on the cellular localization of WNT/β-catenin signaling components and on transcriptional regulation of WNT/β-catenin signaling asks for caution in the interpretation of data derived from the HEK293 cell line.

• Mygland, Line; Mahmuda, Shoshy; Strand, Martin Frank; Olsen, Petter Angell; Aizenshtadt, Aleksandra & Lund, Kaja [Show all 21 contributors for this article] (2021). Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines. iScience. 24(7). doi: 10.1016/j.isci.2021.102807. Full text in Research Archive Show summary

  Small-molecule tankyrase 1 and tankyrase 2 (TNKS1/2) inhibitors are effective antitumor agents in selected tumor cell lines and mouse models. Here, we characterized the response signatures and the in-depth mechanisms for the antiproliferative effect of tankyrase inhibition (TNKSi). The TNKS1/2-specific inhibitor G007-LK was used to screen 537 human tumor cell lines and a panel of particularly TNKSi-sensitive tumor cell lines was identified. Transcriptome, proteome, and bioinformatic analyses revealed the overall TNKSi-induced response signatures in the selected panel. TNKSi-mediated inhibition of wingless-type mammary tumor virus integration site/b-catenin, yes-associated protein 1 (YAP), and phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT signaling was validated and correlated with lost expression of the key oncogene MYC and impaired cell growth. Moreover, we show that TNKSi induces accumulation of TNKS1/2-containing b-catenin degradasomes functioning as core complexes interacting with YAP and angiomotin proteins during attenuation of YAP signaling. These findings provide a contextual and mechanistic framework for using TNKSi in anticancer treatment that warrants further comprehensive preclinical and clinical evaluations.

• Waaler, Jo; Mygland, Line; Tveita, Anders Aune; Strand, Martin Frank; Solberg, Nina & Olsen, Petter Angell [Show all 19 contributors for this article] (2020). Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models. Communications Biology. 3. doi: 10.1038/s42003-020-0916-2. Full text in Research Archive Show summary

  The development of immune checkpoint inhibitors represents a major breakthrough in cancer therapy. Nevertheless, a substantial number of patients fail to respond to checkpoint pathway blockade. Evidence for WNT/β-catenin signaling-mediated immune evasion is found in a subset of cancers including melanoma. Currently, there are no therapeutic strategies available for targeting WNT/β-catenin signaling. Here we show that a specific small-molecule tankyrase inhibitor, G007-LK, decreases WNT/β-catenin and YAP signaling in the syngeneic murine B16-F10 and Clone M-3 melanoma models and sensitizes the tumors to anti-PD-1 immune checkpoint therapy. Mechanistically, we demonstrate that the synergistic effect of tankyrase and checkpoint inhibitor treatment is dependent on loss of β-catenin in the tumor cells, anti-PD-1-stimulated infiltration of T cells into the tumor and induction of an IFNγ- and CD8+ T cell-mediated anti-tumor immune response. Our study uncovers a combinatorial therapeutical strategy using tankyrase inhibition to overcome β-catenin-mediated resistance to immune checkpoint blockade in melanoma.

• Abadpour, Shadab; Aizenshtadt, Aleksandra; Olsen, Petter Angell; Shoji, Kayoko; Wilson, Steven Ray Haakon & Krauss, Stefan [Show all 7 contributors for this article] (2020). Pancreas-on-a-Chip Technology for Transplantation Applications. Current Diabetes Reports. ISSN 1534-4827. 20. doi: 10.1007/s11892-020-01357-1. Full text in Research Archive Show summary

  Abstract Purpose of Review Human pancreas-on-a-chip (PoC) technology is quickly advancing as a platform for complex in vitro modeling of islet physiology. This review summarizes the current progress and evaluates the possibility of using this technology for clinical islet transplantation. Recent Findings PoC microfluidic platforms have mainly shown proof of principle for long-term culturing of islets to study islet function in a standardized format. Advancement in microfluidic design by using imaging-compatible biomaterials and biosensor technology might provide a novel future tool for predicting islet transplantation outcome. Progress in combining islets with other tissue types gives a possibility to study diabetic interventions in a minimal equivalent in vitro environment. Summary Although the field of PoC is still in its infancy, considerable progress in the development of functional systems has brought the technology on the verge of a general applicable tool that may be used to study islet quality and to replace animal testing in the development of diabetes interventions.

• Solberg, Nina; Melheim, Maria; Strand, Martin Frank; Olsen, Petter Angell & Krauss, Stefan (2019). MEK Inhibition Induces Canonical WNT Signaling through YAP in KRAS Mutated HCT-15 Cells, and a Cancer Preventive FOXO3/FOXM1 Ratio in Combination with TNKS Inhibition. Cancers. 11(2), p. 1–19. doi: 10.3390/cancers11020164. Full text in Research Archive Show summary

  The majority of colorectal cancers are induced by subsequent mutations in APC and KRAS genes leading to aberrant activation of both canonical WNT and RAS signaling. However, due to induction of feedback rescue mechanisms some cancers do not respond well to targeted inhibitor treatments. In this study we show that the APC and KRAS mutant human colorectal cancer cell line HCT-15 induces canonical WNT signaling through YAP in a MEK dependent mechanism. This inductive loop is disrupted with combined tankyrase (TNKS) and MEK inhibition. RNA sequencing analysis suggests that combined TNKS/MEK inhibition induces metabolic stress responses in HCT-15 cells promoting a positive FOXO3/FOXM1 ratio to reduce antioxidative and cryoprotective systems.

• Solberg, Nina Therese; Waaler, Jo; Iversen, Kaja Lund; Mygland, Line; Olsen, Peter Angell & Krauss, Stefan (2018). TANKYRASE Inhibition Enhances the Antiproliferative Effect of PI3K and EGFR Inhibition, Mutually Affecting β-CATENIN and AKT Signaling in Colorectal Cancer. Molecular Cancer Research. ISSN 1541-7786. 16(3), p. 1541–1541. doi: 10.1158/1541-7786.MCR-17-0362. Full text in Research Archive
• Solberg, Nina T.; Waaler, Jo; Lund, Kaja; Mygland, Line; Olsen, Petter A. & Krauss, Stefan (2017). TANKYRASE inhibition enhances the antiproliferative effect of PI3K and EGFR inhibition, mutually affecting β-CATENIN and AKT signaling in colorectal cancer. Molecular Cancer Research. ISSN 1541-7786. 16(3), p. 543–553. doi: 10.1158/1541-7786.MCR-17-0362. Full text in Research Archive
• Anumala, Upendra Rao; Waaler, Jo; Nkizinkiko, Yves; Ignatev, Alexander; Lazarow, Katina & Lindemann, Peter [Show all 15 contributors for this article] (2017). Discovery of a Novel Series of Tankyrase Inhibitors by a Hybridization Approach. Journal of Medicinal Chemistry. ISSN 0022-2623. 60(24), p. 10013–10025. doi: 10.1021/acs.jmedchem.7b00883. Full text in Research Archive
• Lund, Kaja; Olsen, Cathrine Elisabeth; Wong, Judith Jing Wen; Olsen, Petter Angell; Solberg, Nina Therese & Høgset, Anders [Show all 8 contributors for this article] (2017). 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin. Journal of Experimental & Clinical Cancer Research. 36, p. 1–18. doi: 10.1186/s13046-017-0662-6. Full text in Research Archive Show summary

  Background Development of resistance to 5-fluorouracil (5-FU) is a major problem in treatment of various cancers including pancreatic cancer. In this study, we reveal important resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma. Methods 5-FU resistant (5-FUR), epithelial-to-mesenchymal-like sub-clones of the wild type pancreatic cancer cell line Panc03.27 were previously generated in our lab. We investigated the cytotoxic effect of the endosomal/lysosomal-localizing photosensitizer TPCS2a (fimaporfin) combined with light (photochemical treatment, PCT) using MTS viability assay, and used fluorescence microscopy to show localization of TPCS2a and to investigate the effect of photodamage of lysosomes. Flow cytometric analysis was performed to investigate uptake of photosensitizer and to assess intracellular ROS levels. Expression and localization of LAMP1 was assessed using RT-qPCR, western blotting, and structured illumination microscopy. MTS viability assay was used to assess the effect of combinations of 5-FU, chloroquine (CQ), and photochemical treatment. Expression of CD105 was investigated using RT-qPCR, western blotting, flow cytometry, and fluorescence microscopy, and co-localization of TPCS2a and anti-CD105-saporin was assessed using microscopy. Lastly, the MTS assay was used to investigate cytotoxic effects of photochemical internalization (PCI) of the anti-CD105-immunotoxin. Results The 5-FUR cell lines display hypersensitivity to PCT, which was linked to increased uptake of TPCS2a, altered lysosomal distribution, lysosomal photodamage and increased expression of the lysosomal marker LAMP-1 in the 5-FUR cells. We show that inhibition of autophagy induced by either chloroquine or lysosomal photodamage increases the sensitivity to 5-FU in the resistant cells. The three 5-FUR sub-clones overexpress Endoglin (CD105). Treatment with the immunotoxin anti-CD105-saporin alone significantly reduced the viability of the CD105-expressing 5-FUR cells, whereas little effect was seen in the CD105-negative non-resistant parental cancer cell lines. Strikingly, using the intracellular drug delivery method photochemical internalization (PCI) by combining light-controlled activation of the TPCS2a with nanomolar levels of CD105-saporin resulted in strong cytotoxic effects in the 5-FUR cell population. Conclusion Our findings suggested that autophagy is an important resistance mechanism against the chemotherapeutic drug 5-FU in pancreatic cancer cells, and that inhibition of the autophagy process, either by CQ or lysosomal photodamage, can contribute to increased sensitivity to 5-FU. For the first time, we demonstrate the promise of PCI-based targeting of CD105 in site-specific elimination of 5-FU resistant pancreatic cancer cells in vitro. In conclusion, PCI-based targeting of CD105 may represent a potent anticancer strategy and should be further evaluated in pre-clinical models.

• Olsen, Peter Angell; Lund, Kaja & Krauss, Stefan (2015). Expression profiling of wild type and β-catenin gene disrupted human BxPC-3 pancreatic adenocarcinoma cells. Genomics Data. 4, p. 150–152. doi: 10.1016/j.gdata.2015.04.010. Full text in Research Archive
• Olsen, Peter Angell; Solberg, Nina; Lund, Kaja; Vehus, Tore; Gelazauskaite, Monika & Wilson, Steven Ray Haakon [Show all 7 contributors for this article] (2014). Implications of targeted genomic disruption of β-catenin in B×PC-3 pancreatic adenocarcinoma cells. PLOS ONE. 9(12). doi: 10.1371/journal.pone.0115496. Full text in Research Archive

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• Kwak, Dongho; Jensenius, Alexander Refsum; Danielsen, Anne; Scholz, Hanne & Olsen, Petter Angell (2023). Music for cells? Rhythmic mechanical stimulations of cell cultures. Universitetet i Oslo. Full text in Research Archive Show summary

  This dissertation investigates how acoustic parameters and musical elements can be generated and manipulated to induce beneficial mechanical stimulations and alterations in cell cultures. The research has been conducted as part of a life science convergence environment, and the theoretical framework and experimental method in this dissertation are derived from three different disciplines: biology, music technology, and physics. The theoretical discussions centre around biological cell sensing mechanisms, the physical limitations and potentiality of audible sound to be used as mechano-acoustic cellular stimuli, and the concept of rhythm from biology and music technology perspectives. The methods include audio signal processing, physical characterisation of the experimental setup, various biological assays, and microscopic image feature extraction. Such a radically interdisciplinary approach culminated in laboratory experiments involving sound vibrations of human cell cultures using a vertical vibration system controlled by synthesized audio signals. The experimental variables included: No Vibration (NV, control), Continuous Vibration (CV), Regular Pulse (RP), and Variable Pulse (VP). The CV condition was categorised as non-rhythmic in this dissertation, while RP and VP were categorised as rhythmic conditions. The results demonstrate alterations in F-actin filament structure (length, thickness, angle) and the tendency of increased levels of cells in the G1-phase cell cycle in vibrated cell cultures. The “effect” was more apparent under the non-rhythmic (CV) condition than rhythmic conditions (RP and VP). The results also show that F-actin filament structural properties are negatively correlated (r < -.9), and the number of cells in the G1-phase cycle is positively correlated (r > .9) in relation to the magnitudes of mechanical parameters (RMS acceleration and shear stress). Nevertheless, the biological mechanism(s) responsible for the observed effects has yet to be characterised. The results from this dissertation inspire further studies on the effects of rhythmic mechanoacoustic stimulation on cellular biological rhythms (e.g., regulation of CLOCK, PER, and CRY genes).

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