Patient-specific microphysiology systems are likely to become a crucial aspect of translational research and precision medicine

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Translational Research ◽  
Precision Medicine ◽  
Cell Types ◽  
Patient Specific ◽  
Crucial Aspect ◽  
Liver Acinus ◽  
Lineage Differentiation ◽  
Liver Model ◽  
High Throughput Experimentation ◽  
Patient Groups

Basic biomedical research, drug discovery and development pipelines address unique "contexts of usage" that include such requirements as high-throughput experimentation, information content, functional biological complexity, and/or clinically relevant disease progression recapitulation. The model was created to more accurately recapitulate key features of the liver acinus structure and functions, including both physical and biochemical environmental cues, in order to help scientists better understand disease mechanisms, identify biomarkers linked to those mechanisms, and better predict drug response and ADME. HBL-MPS liver MPS models, which are designed to optimally mimic the liver acinus as a stand-alone liver model or in conjunction with other organs, are now preferred. Current HBL-MPS models have shown the capability to examine multicellular and temporal-spatial physiological and pathological heterogeneity inside the liver acinus. These MPS models have been utilized to look at crucial disease development pathways connected with NAFLD, type 2 diabetes, and liver metastases. Mature liver acinus cells generated from patient-specific iPSCs provide a significant impediment to full realization of the MPS 'potential capability. Organoid-MPS develop into distinct autologous liver cell types, whereas Structured-MPS are positioned or bioprinted within microfluidic devices. If this project works, Organoid-MPS and/or Structured-MPS might be applied in precision medicine applications. Patient-specific MPS used in preclinical investigations have the capacity to predict clinical response, helping to optimize the selection of patient groups for clinical trials.Despite the fact that MPS is predicted to have a large influence on the future of precision medicine, there are still many barriers to overcome. Also, lineage differentiation efficacy differs between donor lines and individual experiments, resulting in a heterogeneous population of various cell types. However, patient-specific MPS is likely to become a crucial aspect of translational research and precision medicine, considering the rate of technology developments and the availability of clinical validation trials.

scholarly journals Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ibrahim Boussaad ◽  
Gérald Cruciani ◽  
Silvia Bolognin ◽  
Paul Antony ◽  
Claire M. Dording ◽  
...  
Keyword(s):  
Translational Research ◽  
Precision Medicine ◽  
High Throughput ◽  
Neural Progenitor Cells ◽  
Human Fibroblasts ◽  
Cell Types ◽  
Cellular Models ◽  
Automated Platform ◽  
Induced Pluripotent ◽  
Different Cell Types

AbstractPatient-derived cellular models become an increasingly powerful tool to model human diseases for precision medicine approaches. The identification of robust cellular disease phenotypes in these models paved the way towards high throughput screenings (HTS) including the implementation of laboratory advanced automation. However, maintenance and expansion of cells for HTS remains largely manual work. Here, we describe an integrated, complex automated platform for HTS in a translational research setting also designed for maintenance and expansion of different cell types. The comprehensive design allows automation of all cultivation steps and is flexible for development of methods for variable cell types. We demonstrate protocols for controlled cell seeding, splitting and expansion of human fibroblasts, induced pluripotent stem cells (iPSC), and neural progenitor cells (NPC) that allow for subsequent differentiation into different cell types and image-based multiparametric screening. Furthermore, we provide automated protocols for neuronal differentiation of NPC in 2D culture and 3D midbrain organoids for HTS. The flexibility of this multitask platform makes it an ideal solution for translational research settings involving experiments on different patient-derived cellular models for precision medicine.

Uncovering the Diversification of Tissue Engineering on the Emergent Areas of Stem Cells, Nanotechnology and Biomaterials

2020 ◽  
Vol 15 (3) ◽  
pp. 187-201 ◽  
Author(s):  
Sunil K. Dubey ◽  
Amit Alexander ◽  
Munnangi Sivaram ◽  
Mukta Agrawal ◽  
Gautam Singhvi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Immune System ◽  
Clinical Application ◽  
Cell Types ◽  
Patient Specific ◽  
Potential Strategy ◽  
Induced Pluripotent ◽  
Treat All ◽  
The Impact

Damaged or disabled tissue is life-threatening due to the lack of proper treatment. Many conventional transplantation methods like autograft, iso-graft and allograft are in existence for ages, but they are not sufficient to treat all types of tissue or organ damages. Stem cells, with their unique capabilities like self-renewal and differentiate into various cell types, can be a potential strategy for tissue regeneration. However, the challenges like reproducibility, uncontrolled propagation and differentiation, isolation of specific kinds of cell and tumorigenic nature made these stem cells away from clinical application. Today, various types of stem cells like embryonic, fetal or gestational tissue, mesenchymal and induced-pluripotent stem cells are under investigation for their clinical application. Tissue engineering helps in configuring the stem cells to develop into a desired viable tissue, to use them clinically as a substitute for the conventional method. The use of stem cell-derived Extracellular Vesicles (EVs) is being studied to replace the stem cells, which decreases the immunological complications associated with the direct administration of stem cells. Tissue engineering also investigates various biomaterials to use clinically, either to replace the bones or as a scaffold to support the growth of stemcells/ tissue. Depending upon the need, there are various biomaterials like bio-ceramics, natural and synthetic biodegradable polymers to support replacement or regeneration of tissue. Like the other fields of science, tissue engineering is also incorporating the nanotechnology to develop nano-scaffolds to provide and support the growth of stem cells with an environment mimicking the Extracellular matrix (ECM) of the desired tissue. Tissue engineering is also used in the modulation of the immune system by using patient-specific Mesenchymal Stem Cells (MSCs) and by modifying the physical features of scaffolds that may provoke the immune system. This review describes the use of various stem cells, biomaterials and the impact of nanotechnology in regenerative medicine.

Precision medicine in idiopathic pulmonary fibrosis therapy: From translational research to patient-centered care

2021 ◽  
Vol 57 ◽  
pp. 71-80
Author(s):  
Katerina M. Antoniou ◽  
Eliza Tsitoura ◽  
Eirini Vasarmidi ◽  
Emmanouil K. Symvoulakis ◽  
Vassilis Aidinis ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Translational Research ◽  
Precision Medicine ◽  
Patient Centered Care ◽  
Patient Centered ◽  
Centered Care

scholarly journals Bayesian adaptive design of early-phase clinical trials for precision medicine based on cancer biomarkers

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shinjo Yada
Keyword(s):  
Neural Network ◽  
Clinical Trials ◽  
Precision Medicine ◽  
Early Phase ◽  
Patient Specific ◽  
Specific Gene ◽  
Cancer Type ◽  
Background Characteristics ◽  
Number Of Patients ◽  
Early Phase Clinical Trials

Abstract Cancer tissue samples obtained via biopsy or surgery were examined for specific gene mutations by genetic testing to inform treatment. Precision medicine, which considers not only the cancer type and location, but also the genetic information, environment, and lifestyle of each patient, can be applied for disease prevention and treatment in individual patients. The number of patient-specific characteristics, including biomarkers, has been increasing with time; these characteristics are highly correlated with outcomes. The number of patients at the beginning of early-phase clinical trials is often limited. Moreover, it is challenging to estimate parameters of models that include baseline characteristics as covariates such as biomarkers. To overcome these issues and promote personalized medicine, we propose a dose-finding method that considers patient background characteristics, including biomarkers, using a model for phase I/II oncology trials. We built a Bayesian neural network with input variables of dose, biomarkers, and interactions between dose and biomarkers and output variables of efficacy outcomes for each patient. We trained the neural network to select the optimal dose based on all background characteristics of a patient. Simulation analysis showed that the probability of selecting the desirable dose was higher using the proposed method than that using the naïve method.

scholarly journals Immunotherapy as a Precision Medicine Tool for the Treatment of Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 173
Author(s):  
Maria Adamaki ◽  
Vassilios Zoumpourlis
Keyword(s):  
Prostate Cancer ◽  
Precision Medicine ◽  
Checkpoint Inhibitors ◽  
Invasive Disease ◽  
Patient Specific ◽  
Treatment Alternative ◽  
Substantial Evidence ◽  
Significant Survival ◽  
Localized Disease ◽  
Specific Antigens

Prostate cancer (PCa) is the most frequently diagnosed type of cancer among Caucasian males over the age of 60 and is characterized by remarkable heterogeneity and clinical behavior, ranging from decades of indolence to highly lethal disease. Despite the significant progress in PCa systemic therapy, therapeutic response is usually transient, and invasive disease is associated with high mortality rates. Immunotherapy has emerged as an efficacious and non-toxic treatment alternative that perfectly fits the rationale of precision medicine, as it aims to treat patients on the basis of patient-specific, immune-targeted molecular traits, so as to achieve the maximum clinical benefit. Antibodies acting as immune checkpoint inhibitors and vaccines entailing tumor-specific antigens seem to be the most promising immunotherapeutic strategies in offering a significant survival advantage. Even though patients with localized disease and favorable prognostic characteristics seem to be the ones that markedly benefit from such interventions, there is substantial evidence to suggest that the survival benefit may also be extended to patients with more advanced disease. The identification of biomarkers that can be immunologically targeted in patients with disease progression is potentially amenable in this process and in achieving significant advances in the decision for precision treatment of PCa.

Use of Circulating Cell-Free DNA to Guide Precision Medicine in Patients with Colorectal Cancer

2021 ◽  
Vol 72 (1) ◽  
pp. 399-413
Author(s):  
Van K. Morris ◽  
John H. Strickler
Keyword(s):  
Colorectal Cancer ◽  
Precision Medicine ◽  
Residual Disease ◽  
Cost Effective ◽  
Patient Specific ◽  
Blood Draw ◽  
Cell Free Dna ◽  
Free Dna ◽  
Metastatic Setting ◽  
Diagnostic Technology

Patient-specific biomarkers form the foundation of precision medicine strategies. To realize the promise of precision medicine in patients with colorectal cancer (CRC), access to cost-effective, convenient, and safe assays is critical. Improvements in diagnostic technology have enabled ultrasensitive and specific assays to identify cell-free DNA (cfDNA) from a routine blood draw. Clinicians are already employing these minimally invasive assays to identify drivers of therapeutic resistance and measure genomic heterogeneity, particularly when tumor tissue is difficult to access or serial sampling is necessary. As cfDNA diagnostic technology continues to improve, more innovative applications are anticipated. In this review, we focus on four clinical applications for cfDNA analysis in the management of CRC: detecting minimal residual disease, monitoring treatment response in the metastatic setting, identifying drivers of treatment sensitivity and resistance, and guiding therapeutic strategies to overcome resistance.

Abstract 289: Transcriptomic Analysis of Inter- and Intra-patient Variation in Human iPSCs: Platform for Precision Medicine to Predict Drug Toxicity

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Elena Matsa ◽  
Paul W Burridge ◽  
Kun-Hsing Yu ◽  
Haodi Wu ◽  
Vittavat Termglinchan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Precision Medicine ◽  
Disease Modeling ◽  
Sendai Virus ◽  
Expression Profiles ◽  
Cardiac Differentiation ◽  
Patient Specific ◽  
Specific Gene ◽  
Drug Induced ◽  
Human Ipscs

Rapid improvements in human induced pluripotent stem cell (hiPSC) differentiation methodologies have allowed previously unattainable access to high-purity, patient-specific cardiomyocytes (CMs) for use in disease modeling, cardiac regeneration, and drug testing. In the present study, we investigate the ability of hiPSC-derived cardiomyocytes (hiPSC-CMs) to reflect the donor’s genetic identity and serve as preclinical functional readout platforms for precision medicine. We used footprint-free Sendai virus to create two separate hiPSC clones from the fibroblasts of five different individuals lacking known mutations associated with cardiovascular disease. Whole genome expression profiling of hiPSC-CMs showed that inter-patient variation was greater than intra-patient variation, thereby verifying that reprogramming and cardiac differentiation technologies can preserve patient-specific gene expression signatures. Gene ontologies (GOs) accounting for inter-patient variation were mostly metabolic or epigenetic. Toxicology analysis based on gene expression profiles predicted patient-specific susceptibility of hiPSC-CMs to cardiotoxicity, and functional assays using drugs targeting key regulators in pathways predicted to produce cardiotoxicity showed inter-patient differential responses in hiPSC-CMs. Our data suggest that hiPSC-CMs can be used in vitro to predict and help prevent patient-specific drug-induced cardiotoxicity, potentially enabling personalized patient consultation in the future.

scholarly journals Designer blood: creating hematopoietic lineages from embryonic stem cells

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1265-1275 ◽  
Author(s):  
Abby L. Olsen ◽  
David L. Stachura ◽  
Mitchell J. Weiss
Keyword(s):  
Stem Cells ◽  
Es Cells ◽  
Embryonic Stem ◽  
Basic Research ◽  
Cell Types ◽  
Patient Specific ◽  
Es Cell ◽  
Blood Disorders ◽  
Hematopoietic Stem

Embryonic stem (ES) cells exhibit the remarkable capacity to become virtually any differentiated tissue upon appropriate manipulation in culture, a property that has been beneficial for studies of hematopoiesis. Until recently, the majority of this work used murine ES cells for basic research to elucidate fundamental properties of blood-cell development and establish methods to derive specific mature lineages. Now, the advent of human ES cells sets the stage for more applied pursuits to generate transplantable cells for treating blood disorders. Current efforts are directed toward adapting in vitro hematopoietic differentiation methods developed for murine ES cells to human lines, identifying the key interspecies differences in biologic properties of ES cells, and generating ES cell-derived hematopoietic stem cells that are competent to repopulate adult hosts. The ultimate medical goal is to create patient-specific and generic ES cell lines that can be expanded in vitro, genetically altered, and differentiated into cell types that can be used to treat hematopoietic diseases.

scholarly journals Models of cardiovascular surgery biobanking to facilitate translational research and precision medicine

2021 ◽  
Author(s):  
YingYan Zhu ◽  
Dan Jackson ◽  
Benjamin Hunter ◽  
Lorna Beattie ◽  
Lisa Turner ◽  
...  
Keyword(s):  
Translational Research ◽  
Precision Medicine ◽  
Cardiovascular Surgery
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