Injectable, scalable 3D tissue-engineered model of marrow hematopoiesis

Tavakol, Daniel Naveed; Tratwal, Josefine; Bonini, Fabien; Genta, Martina; Campos, Vasco; Burch, Patrick A.; Hoehnel, Sylke; Béduer, Amélie; Alessandrini, Marco; Naveiras, Olaia; Braschler, Thomas

doi:10.1016/j.biomaterials.2019.119665

Cited by 30 publications

(33 citation statements)

References 62 publications

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“…A further promising approach for more strongly anchorage-dependent cells is the use of a suspension of microscaffold carriers. 21,25,26 While improving aspects of cell survival, these studies do not address the question of how a fully organized and mature neural network might be transplanted. Nerve-guide inspired cylindrical sheaths have been shown to successfully maintain mature tissue integrity [27][28][29] .…”

Section: Introductionmentioning

confidence: 99%

“…To provide true 3D transplantation, the use of slowly biodegradable highly porous biomaterial scaffolds has been proposed 20,21 : such scaffolds can be used for robust culture of primary neurons and neuron-like cells in vitro, and have been shown to enhance survival during in-vitro handling procedures 20,21 . To facilitate minimally invasive cell delivery in vivo, cryogels as a class of particularly rugged macroporous hydrogels have been advanced 26,31,32 . Cryogels are synthesized by freezing a hydrogel premix, following by polymerization in the cold 33 .…”

Section: Introductionmentioning

confidence: 99%

“…Upon thawing, highly resilient sponge-like structures with macropores on the order of tens to hundreds of micrometers are obtained. 32, 34 The extreme porosity allows the desired favourable interaction with the surrounding tissue, including colonization and vascularization of the pore space 26,34 and facile exchange with the surrounding tissue 35 . A series of cryogels, including gelatin-laminin, heparin, alginate and CMC-based cryogels were previously demonstrated to be compatible with neuronal culture 20,21,36 .…”

Section: Introductionmentioning

confidence: 99%

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Neurothreads: Cryogel carrier-based differentiation and delivery of mature neurons in the treatment of Parkinson’s disease

Филиппова

Bonini

Efremova

et al. 2020

Preprint

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Keywords in-vivo neuronal transplantation, cryogel scaffold, stem cell differentiation, Parkinson's disease, hydrogel functionalization, stereotactic injection Total Word Count: 7750 (manuscript, excluding figure captions and references) AbstractWe present in-vivo transplantation of mature dopaminergic neurons by means of macroporous, injectable carriers, to enhance cell therapy in Parkinson's disease. The carriers are synthesized by crosslinking carboxymethylcellulose at subzero temperatures, resulting in cylindrical, highly resilient porous cryogels, which we term Neurothreads. We develop efficient covalent immobilization of the neural adhesion proteins laminin 111, collagen IV and fibronectin, as well as of the extracellular matrix extract Matrigel to the Neurothreads. We observe the highest neural spreading on laminin 111 and Matrigel. We show compatibility with established dopaminergic differentiation of both HS420 human embryonic stem cells and the LUHMES midbrain model cell line. The porous Neurothread carriers withstand compression during minimally invasive stereotactic injection, and ensure viability of mature neurons including extended neurites. Implanted into the striatum in mice, the Neurothreads enable survival of transplanted mature neurons obtained by directed differentiation of the HS420 human embryonic stem cells, as a dense tissue in situ, including dopaminergic cells. With the successful in-vivo transfer of intact, mature and fully open 3D neural networks, we provide a powerful tool to extend established differentiation protocols to higher maturity and to enhance preconfigured neural network transplantation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neurothreads: Cryogel carrier-based differentiation and delivery of mature neurons in the treatment of Parkinson’s disease

Филиппова

Bonini

Efremova

et al. 2020

Preprint

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“…Nonetheless, the development of a functionally effective model capable of showing BMN diversity and dynamism with the translational potential for disease modeling is still challenging. No single approach has been adopted as the standard in the field [ 63 , 64 , 65 ], however, different models have succeeded in reproducing some particular and restricted aspects of specific BM contexts. For example, the first attempts at reproducing cell-cell interactions started with the co-culture of HSCs and different BMN-forming cells, such as ECs, OBs or MSCs [ 66 , 67 , 68 ].…”

Section: Advances In Bm Modelsmentioning

confidence: 99%

“…However, the combinatorial approaches are the most commonly used [ 74 , 75 , 76 ]. When moving forward towards the reviewed cell engineered approaches [ 65 , 77 , 78 ] it appears that in vivo-mediated vascularization, native ECM remodeling or including different cell types in the engineered models will indirectly lead to better functional compartmentalization than the initial design. Therefore, compartmentalization seems necessary to mimic functional BMN differentiation either by directly including it in the model or by indirect cell-mediated remodeling ( Box 5 ).…”

Section: Unresolved Questions In Modeling Bm and Non-solid Tumorsmentioning

confidence: 99%

In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

Clara-Trujillo

Ferrer

Ribelles

2020

IJMS

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In hematological malignancies, leukemias or myelomas, malignant cells present bone marrow (BM) homing, in which the niche contributes to tumor development and drug resistance. BM architecture, cellular and molecular composition and interactions define differential microenvironments that govern cell fate under physiological and pathological conditions and serve as a reference for the native biological landscape to be replicated in engineered platforms attempting to reproduce blood cancer behavior. This review summarizes the different models used to efficiently reproduce certain aspects of BM in vitro; however, they still lack the complexity of this tissue, which is relevant for fundamental aspects such as drug resistance development in multiple myeloma. Extracellular matrix composition, material topography, vascularization, cellular composition or stemness vs. differentiation balance are discussed as variables that could be rationally defined in tissue engineering approaches for achieving more relevant in vitro models. Fully humanized platforms closely resembling natural interactions still remain challenging and the question of to what extent accurate tissue complexity reproduction is essential to reliably predict drug responses is controversial. However, the contributions of these approaches to the fundamental knowledge of non-solid tumor biology, its regulation by niches, and the advance of personalized medicine are unquestionable.

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Engineered Tissue Models to Replicate Dynamic Interactions within the Hematopoietic Stem Cell Niche

Gilchrist

Harley

2022

Adv Healthcare Materials

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Hematopoietic stem cells are the progenitors of the blood and immune system and represent the most widely used regenerative therapy. However, their rarity and limited donor base necessitate the design of ex vivo systems that support HSC expansion without the loss of long-term stem cell activity. This review describes recent advances in biomaterials systems to replicate features of the hematopoietic niche. Inspired by the native bone marrow, these instructive biomaterials provide stimuli and cues from cocultured niche-associated cells to support HSC encapsulation and expansion. Engineered systems increasingly enable study of the dynamic nature of the matrix and biomolecular environment as well as the role of cell-cell signaling (e.g., autocrine feedback vs paracrine signaling between dissimilar cells). The inherent coupling of material properties, biotransport of cell-secreted factors, and cell-mediated remodeling motivate dynamic biomaterial systems as well as characterization and modeling tools capable of evaluating a temporally evolving tissue microenvironment. Recent advances in HSC identification and tracking, model-based experimental design, and single-cell culture platforms facilitate the study of the effect of constellations of matrix, cell, and soluble factor signals on HSC fate. While inspired by the HSC niche, these tools are amenable to the broader stem cell engineering community.

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Injectable, scalable 3D tissue-engineered model of marrow hematopoiesis

Cited by 30 publications

References 62 publications

Neurothreads: Cryogel carrier-based differentiation and delivery of mature neurons in the treatment of Parkinson’s disease

Neurothreads: Cryogel carrier-based differentiation and delivery of mature neurons in the treatment of Parkinson’s disease

In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

Engineered Tissue Models to Replicate Dynamic Interactions within the Hematopoietic Stem Cell Niche

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