Macrophages Derived From Human Induced Pluripotent Stem Cells: The Diversity of Protocols, Future Prospects, and Outstanding Questions

Lyadova, Irina V.; Gerasimova, Tatiana; Nenasheva, Tatiana A.

doi:10.3389/fcell.2021.640703

Cited by 33 publications

(38 citation statements)

References 241 publications

(484 reference statements)

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“…Once mesoderm is formed, the cells are cultured in conditions that favor the generation of hematopoietic progenitors (HPPs), their myeloid specification and iMph terminal differentiation. To drive the iMph differentiation process, various protocols have been elaborated and are currently used (reviewed in [ 21 ]). Their variety can be reduced to four main types.…”

Section: Principles Of Imph Generation and The Advantages Of The Modelmentioning

confidence: 99%

“…iMphs obtained using different protocols have a typical macrophage morphology (large vacuolated cells with pseudopodia), express a typical macrophage phenotype (CD14 + CD11b + CD45 + ) and execute the main macrophage functions, such as phagocytosis and the secretion of pro- and anti-inflammatory cytokines (reviewed in [ 21 , 44 ] and [ 27 – 29 , 37 , 45 – 47 ]).…”

Section: Principles Of Imph Generation and The Advantages Of The Modelmentioning

confidence: 99%

“…Over the last few years, the number of studies aimed at iMph generation and analysis has been rapidly growing, leading to the appearance of new effective protocols of iMph differentiation, a deeper understanding of iMph biology and the emergence of new promising iMph applications. Recently, we have reviewed the principles and methodological aspects of iMph generation [ 21 ]. Here, we systemize the most actively developed areas of human iMph studies and discuss the prospects and limitations in this context.…”

Section: Introductionmentioning

confidence: 99%

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Macrophages derived from pluripotent stem cells: prospective applications and research gaps

Lyadova

Vasiliev

2022

Cell Biosci

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Induced pluripotent stem cells (iPSCs) represent a valuable cell source able to give rise to different cell types of the body. Among the various pathways of iPSC differentiation, the differentiation into macrophages is a recently developed and rapidly growing technique. Macrophages play a key role in the control of host homeostasis. Their dysfunction underlies many diseases, including hereditary, infectious, oncological, metabolic and other disorders. Targeting macrophage activity and developing macrophage-based cell therapy represent promising tools for the treatment of many pathological conditions. Macrophages generated from human iPSCs (iMphs) provide great opportunities in these areas. The generation of iMphs is based on a step-wise differentiation of iPSCs into mesoderm, hematopoietic progenitors, myeloid monocyte-like cells and macrophages. The technique allows to obtain standardizable populations of human macrophages from any individual, scale up macrophage production and introduce genetic modifications, which gives significant advantages over the standard source of human macrophages, monocyte-derived macrophages. The spectrum of iMph applications is rapidly growing. iMphs have been successfully used to model hereditary diseases and macrophage-pathogen interactions, as well as to test drugs. iMph use for cell therapy is another promising and rapidly developing area of research. The principles and the details of iMph generation have recently been reviewed. This review systemizes current and prospective iMph applications and discusses the problem of iMph safety and other issues that need to be explored before iMphs become clinically applicable.

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Section: Principles Of Imph Generation and The Advantages Of The Modelmentioning

confidence: 99%

Section: Principles Of Imph Generation and The Advantages Of The Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Macrophages derived from pluripotent stem cells: prospective applications and research gaps

Lyadova

Vasiliev

2022

Cell Biosci

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“…Whether this is also true for human KCs is less well understood. Multiple studies have been reported wherein hPSCs are fated to the monocyte/macrophage lineage (reviewed in [120,121]). However, only a single study was reported wherein hPSCs were differentiated into cells with KC-like features [122].…”

Section: Kupffer Cellsmentioning

confidence: 99%

Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery

Tricot

Verfaillie

Kumar

2022

Cells

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The pharmaceutical industry is in high need of efficient and relevant in vitro liver models, which can be incorporated in their drug discovery pipelines to identify potential drugs and their toxicity profiles. Current liver models often rely on cancer cell lines or primary cells, which both have major limitations. However, the development of human induced pluripotent stem cells (hiPSCs) has created a new opportunity for liver disease modeling, drug discovery and liver toxicity research. hiPSCs can be differentiated to any cell of interest, which makes them good candidates for disease modeling and drug discovery. Moreover, hiPSCs, unlike primary cells, can be easily genome-edited, allowing the creation of reporter lines or isogenic controls for patient-derived hiPSCs. Unfortunately, even though liver progeny from hiPSCs has characteristics similar to their in vivo counterparts, the differentiation of iPSCs to fully mature progeny remains highly challenging and is a major obstacle for the full exploitation of these models by pharmaceutical industries. In this review, we discuss current liver-cell differentiation protocols and in vitro iPSC-based liver models that could be used for disease modeling and drug discovery. Furthermore, we will discuss the challenges that still need to be overcome to allow for the successful implementation of these models into pharmaceutical drug discovery platforms.

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“…Indeed, microglia and peripheral macrophages have different developmental origins and are in very different environments in vivo , suggesting that different protocols must be set up to mimic the diverse macrophage subtypes. Many reports and reviews describe and compare protocols allowing the generation of functional macrophage-like cells ( Haenseler and Rajendran, 2019 ; Hasselmann and Blurton-Jones, 2020 ; Hedegaard et al, 2020 ; Lyadova et al, 2021 ). Clearly, iPSC require specific environmental signals for proper differentiation and maintenance of their identity ( Bohlen et al, 2017 ; Gosselin et al, 2017 ), suggesting that for ALS and FTD studies, iPS-derived microglia have to be co-cultured with either MNs or cortical neurons, respectively.…”

Section: Ipsc To Model Immune Reactivity In Amyotrophic Lateral Sclerosis and Frontotemporal Dementiamentioning

confidence: 99%

Neuroinflammation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia and the Interest of Induced Pluripotent Stem Cells to Study Immune Cells Interactions With Neurons

Liu

Karpf

Bohl

2021

Front. Mol. Neurosci.

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Inflammation is a shared hallmark between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). For long, studies were conducted on tissues of post-mortem patients and neuroinflammation was thought to be only bystander result of the disease with the immune system reacting to dying neurons. In the last two decades, thanks to improving technologies, the identification of causal genes and the development of new tools and models, the involvement of inflammation has emerged as a potential driver of the diseases and evolved as a new area of intense research. In this review, we present the current knowledge about neuroinflammation in ALS, ALS-FTD, and FTD patients and animal models and we discuss reasons of failures linked to therapeutic trials with immunomodulator drugs. Then we present the induced pluripotent stem cell (iPSC) technology and its interest as a new tool to have a better immunopathological comprehension of both diseases in a human context. The iPSC technology giving the unique opportunity to study cells across differentiation and maturation times, brings the hope to shed light on the different mechanisms linking neurodegeneration and activation of the immune system. Protocols available to differentiate iPSC into different immune cell types are presented. Finally, we discuss the interest in studying monocultures of iPS-derived immune cells, co-cultures with neurons and 3D cultures with different cell types, as more integrated cellular approaches. The hope is that the future work with human iPS-derived cells helps not only to identify disease-specific defects in the different cell types but also to decipher the synergistic effects between neurons and immune cells. These new cellular tools could help to find new therapeutic approaches for all patients with ALS, ALS-FTD, and FTD.

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Macrophages Derived From Human Induced Pluripotent Stem Cells: The Diversity of Protocols, Future Prospects, and Outstanding Questions

Cited by 33 publications

References 241 publications

Macrophages derived from pluripotent stem cells: prospective applications and research gaps

Macrophages derived from pluripotent stem cells: prospective applications and research gaps

Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery

Neuroinflammation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia and the Interest of Induced Pluripotent Stem Cells to Study Immune Cells Interactions With Neurons

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