Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells

Karimpoor, Mahroo; Yebra-Fernandez, Eva; Parhizkar, Maryam; Orlu, Mine; Craig, Duncan Q.M.; Khorashad, Jamshid S.; Edirisinghe, Mohan

doi:10.1098/rsif.2017.0928

Cited by 11 publications

(16 citation statements)

References 38 publications

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“…AML cell lines and progenitors in the scaffold pores displayed an altered phenotype and increased resistance to imatinib and doxorubicin when cultured in 3D compared to 2D [193] HA + collagen I Co-culture MSCs either from patients (AML-MSCs) or h-MSCs + OBs + ECs + AML blasts The scaffold sustained the long-term (21 days) culture of the blast cells. AML-MSCs exhibited higher proliferation compared to hMSCs…”

Section: In Vitro Scaffold/matrix-based Models Of Acute Myeloid Leukemiamentioning

confidence: 99%

Modelling acute myeloid leukemia (AML): What’s new? A transition from the classical to the modern

Dozzo

Galvin

Shin

et al. 2022

Drug Deliv. and Transl. Res.

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Acute myeloid leukemia (AML) is a heterogeneous malignancy affecting myeloid cells in the bone marrow (BM) but can spread giving rise to impaired hematopoiesis. AML incidence increases with age and is associated with poor prognostic outcomes. There has been a disconnect between the success of novel drug compounds observed in preclinical studies of hematological malignancy and less than exceptional therapeutic responses in clinical trials. This review aims to provide a state-of-the-art overview on the different preclinical models of AML available to expand insights into disease pathology and as preclinical screening tools. Deciphering the complex physiological and pathological processes and developing predictive preclinical models are key to understanding disease progression and fundamental in the development and testing of new effective drug treatments. Standard scaffold-free suspension models fail to recapitulate the complex environment where AML occurs. To this end, we review advances in scaffold/matrix-based 3D models and outline the most recent advances in on-chip technology. We also provide an overview of clinically relevant animal models and review the expanding use of patient-derived samples, which offer the prospect to create more “patient specific” screening tools either in the guise of 3D matrix models, microphysiological “organ-on-chip” tools or xenograft models and discuss representative examples. Graphical abstract

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Section: In Vitro Scaffold/matrix-based Models Of Acute Myeloid Leukemiamentioning

confidence: 99%

Modelling acute myeloid leukemia (AML): What’s new? A transition from the classical to the modern

Dozzo

Galvin

Shin

et al. 2022

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

show abstract

“…This shows the versatility of the application of highly porous 3D foams for bone tissue engineering. Another study detailed about the fabrication of alginate foam‐based scaffold containing bone marrow (BM) like components that were used for investigating doxorubicin drug sensitivity against leukemia cell lines (K572 and HL 60; Karimpoor et al, 2018). These examples show that the gas foaming technique allows a new magnitude of emerging biomimetic scaffolds with enhanced properties.…”

Section: Techniques For the Preparation Of Scaffoldsmentioning

confidence: 99%

Fabrication techniques of biomimetic scaffolds in three‐dimensional cell culture: A review

Badekila

Kini

Jaiswal

2020

Journal Cellular Physiology

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In the last four decades, several researchers worldwide have routinely and meticulously exercised cell culture experiments in two-dimensional (2D) platforms. Using traditionally existing 2D models, the therapeutic efficacy of drugs has been inappropriately validated due to the failure in generating the precise therapeutic response. Fortunately, a 3D model addresses the foregoing limitations by recapitulating the in vivo environment. In this context, one has to contemplate the design of an appropriate scaffold for favoring the organization of cell microenvironment. Instituting pertinent model on the platter will pave way for a precise mimicking of in vivo conditions. It is because animal cells in scaffolds oblige spontaneous formation of 3D colonies that molecularly, phenotypically, and histologically resemble the native environment. The 3D culture provides insight into the biochemical aspects of cell-cell communication, plasticity, cell division, cytoskeletal reorganization, signaling mechanisms, differentiation, and cell death. Focusing on these criteria, this paper discusses in detail, the diversification of polymeric scaffolds based on their available resources. The paper also reviews the well-founded and latest techniques of scaffold fabrication, and their applications pertaining to tissue engineering, drug screening, and tumor model development.

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“…Synthetic ECMs also offer strategies to recreate complex 3D niches to study disease in vitro . For example, an alginate foam that mimicked the 3D microporosity of the bone marrow microenvironment enhanced differentiation of myeloid precursors from a leukemia cell line and improved prediction of chemotherapeutic resistance, as compared to a 2D culture [ 214 ]. Overall, the tailorability of these synthetic ECM approaches enables understanding of the role that mechanobiology plays in disease progression, offering insights into disease mechanisms and potential drug development platforms.…”

Section: Engineering Advances: Assembling Advanced In Vitromentioning

confidence: 99%

Engineered tissues and strategies to overcome challenges in drug development

Khalil

Jaenisch

Mooney

2020

Advanced Drug Delivery Reviews

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Current preclinical studies in drug development utilize high-throughput in vitro screens to identify lead drug candidates, followed by both in vitro and in vivo models to predict lead candidates' pharmacokinetic and pharmacodynamic properties. The goal of these studies is to reduce the number of lead drug candidates down to the most likely to succeed in later human clinical trials. However, only 1 in 10 drug candidates that emerge from preclinical studies will succeed and become an approved therapeutic. Lack of efficacy or undetected toxicity represents roughly 75% of the causes for these failures, despite these parameters being the primary exclusion criteria in preclinical studies. Recently, advances in both biology and engineering have created new tools for constructing new preclinical models. These models can complement those used in current preclinical studies by helping to create more realistic representations of human tissues in vitro and in vivo . In this review, we describe current preclinical models to identify their value and limitations and then discuss select areas of research where improvements in preclinical models are particularly needed to advance drug development. Following this, we discuss design considerations for constructing preclinical models and then highlight recent advances in these efforts. Taken together, we aim to review the advances as of 2020 surrounding the prospect of biological and engineering tools for adding enhanced biological relevance to preclinical studies to aid in the challenges of failed drug candidates and the burden this poses on the drug development enterprise and thus healthcare.

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Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells

Cited by 11 publications

References 38 publications

Modelling acute myeloid leukemia (AML): What’s new? A transition from the classical to the modern

Modelling acute myeloid leukemia (AML): What’s new? A transition from the classical to the modern

Fabrication techniques of biomimetic scaffolds in three‐dimensional cell culture: A review

Engineered tissues and strategies to overcome challenges in drug development

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