Applications of Bioengineered 3D Tissue and Tumor Organoids in Drug Development and Precision Medicine: Current and Future

Devarasetty, Mahesh; Mazzocchi, Andrea; Skardal, Aleksander

doi:10.1007/s40259-017-0258-x

Cited by 56 publications

(53 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ultimately, we hope that patient-derived tumor organoids (PTOs) can be deployed in in vitro drug screening studies to be used as diagnostic tests of sorts, generating empirical drug response data specific to each patient that can help oncologists choose the best drug for a given tumor. As described above, we have performed such in vitro drug screens with PTOs for a number of tumor types [20][21][22][23]42]. However, being able to scale up, automate, and improve the consistency of these PTOs is a hurdle [43].…”

Section: Patient-derived Tumor Organoid Bioprinting and Chemotherapy mentioning

confidence: 99%

Immersion Bioprinting of Tumor Organoids in Multi-Well Plates for Increasing Chemotherapy Screening Throughput

et al. 2020

Self Cite

View full text Add to dashboard Cite

The current drug development pipeline takes approximately fifteen years and $2.6 billion to get a new drug to market. Typically, drugs are tested on two-dimensional (2D) cell cultures and animal models to estimate their efficacy before reaching human trials. However, these models are often not representative of the human body. The 2D culture changes the morphology and physiology of cells, and animal models often have a vastly different anatomy and physiology than humans. The use of bioengineered human cell-based organoids may increase the probability of success during human trials by providing human-specific preclinical data. They could also be deployed for personalized medicine diagnostics to optimize therapies in diseases such as cancer. However, one limitation in employing organoids in drug screening has been the difficulty in creating large numbers of homogeneous organoids in form factors compatible with high-throughput screening (e.g., 96-and 384-well plates). Bioprinting can be used to scale up deposition of such organoids and tissue constructs. Unfortunately, it has been challenging to 3D print hydrogel bioinks into small-sized wells due to well-bioink interactions that can result in bioinks spreading out and wetting the well surface instead of maintaining a spherical form. Here, we demonstrate an immersion printing technique to bioprint tissue organoids in 96-well plates to increase the throughput of 3D drug screening. A hydrogel bioink comprised of hyaluronic acid and collagen is bioprinted into a viscous gelatin bath, which blocks the bioink from interacting with the well walls and provides support to maintain a spherical form. This method was validated using several cancerous cell lines, and then applied to patient-derived glioblastoma (GBM) and sarcoma biospecimens for drug screening.

show abstract

Section: Patient-derived Tumor Organoid Bioprinting and Chemotherapy mentioning

confidence: 99%

Immersion Bioprinting of Tumor Organoids in Multi-Well Plates for Increasing Chemotherapy Screening Throughput

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, they fail to incorporate human tumor stroma (Dobrolecki et al, ). Bioengineered 3D platforms using human patient‐derived cells can better mimic the cell–cell, cell‐ECM, and mechanical interactions of in vivo tissue, and are thus more suitable for mechanistic research and applications such as improving personalized medicine approaches (Devarasetty, Mazzocchi, & Skardal, ; Mazzocchi, Soker, & Skardal, ). Importantly, in recent years, there has been a rapid advance in the integration of 3D tissue constructs and organoids with microfluidic device architectures, resulting in a variety of tissue‐ and tumor‐on‐a‐chip systems.…”

Section: Introductionmentioning

confidence: 99%

A multi‐site metastasis‐on‐a‐chip microphysiological system for assessing metastatic preference of cancer cells

Aleman

Skardal

2018

Biotech & Bioengineering

Self Cite

101

View full text Add to dashboard Cite

Metastatic disease remains one of the primary reasons for cancer-related deaths, yet the majority of in vitro cancer models focus on the primary tumor sites. Here, we describe a metastasis-on-a-chip device that houses multiple bioengineered threedimensional (3D) organoids, established by a 3D photopatterning technique employing extracellular matrix-derived hydrogel biomaterials. Specifically, cancer cells begin in colorectal cancer (CRC) organoid, which resides in a single microfluidic chamber connected to multiple downstream chambers in which liver, lung, and endothelial constructs are housed. Under recirculating fluid flow, tumor cells grow in the primary site, eventually enter circulation, and can be tracked via fluorescent imaging.Importantly, we describe that in the current version of this platform, HCT116 CRC cells preferentially home to the liver and lung constructs; the corresponding organs of which CRC metastases arise the most in human patients. We believe that in subsequent studies this platform can be implemented to better understand the mechanisms underlying metastasis, perhaps resulting in the identification of targets for intervention. K E Y W O R D Scancer, microfluidics, organ-on-a-chip, three-dimensional (3D) in vitro model, tumor-on-a-chip

show abstract

“…In addition to the generation of cell sheets and patches, biomaterials are used for the construction of complex, biomimetic 3-dimensional tissue structures or organoids, a process termed cardiac tissue engineering [449,450]. For in vitro generation of functional heart tissue, various cell types are required.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Müller

Lemcke

Dávid

2018

Cell Physiol Biochem

161

137

View full text Add to dashboard Cite

A large number of clinical trials have shown stem cell therapy to be a promising therapeutic approach for the treatment of cardiovascular diseases. Since the first transplantation into human patients, several stem cell types have been applied in this field, including bone marrow derived stem cells, cardiac progenitors as well as embryonic stem cells and their derivatives. However, results obtained from clinical studies are inconsistent and stem cell-based improvement of heart performance and cardiac remodeling was found to be quite limited. In order to optimize stem cell efficiency, it is crucial to elucidate the underlying mechanisms mediating the beneficial effects of stem cell transplantation. Based on these mechanisms, researchers have developed different improvement strategies to boost the potency of stem cell repair and to generate the “next generation” of stem cell therapeutics. Moreover, since cardiovascular diseases are complex disorders including several disease patterns and pathologic mechanisms it may be difficult to provide a uniform therapeutic intervention for all subgroups of patients. Therefore, future strategies should aim at more personalized SC therapies in which individual disease parameters influence the selection of optimal cell type, dosage and delivery approach.

show abstract

Applications of Bioengineered 3D Tissue and Tumor Organoids in Drug Development and Precision Medicine: Current and Future

Cited by 56 publications

References 99 publications

Immersion Bioprinting of Tumor Organoids in Multi-Well Plates for Increasing Chemotherapy Screening Throughput

Immersion Bioprinting of Tumor Organoids in Multi-Well Plates for Increasing Chemotherapy Screening Throughput

A multi‐site metastasis‐on‐a‐chip microphysiological system for assessing metastatic preference of cancer cells

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

Contact Info

Product

Resources

About