Microengineering double layer hydrogel structures towards the recapitulation of the hematopoietic stem cell niche

Carreras, Pilar; Chaves, Rodrigo Cortrim; Gallardo, Miguel; Ortiz, Alejandra; López, Joaquín Martínez; Sia, Samuel K.

doi:10.1016/j.scib.2018.09.003

Cited by 6 publications

(15 citation statements)

References 15 publications

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“…Hence, when the inner core droplet reaches the area of the second droplet production, the two droplets (one gelated and another ungelated) passively mix along the meander, generating a double layered hydrogel bead. This process was described in detail in the previously reported work [1].…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have been reported for the recapitulation of the stem cell microniche by droplet microfluidics [1]. Ex vivo maintenance and expansion of primary human multiple myeloma (MM) cells have presented several difficulties [2] due to the lack of an in vitro method able to reproduce the complex bone marrow niche microenvironment.…”

Section: Introductionmentioning

confidence: 99%

“…Recently we reported a method in which a double layered hydrogel bead able to accommodate adult stem cells where controlled generation of the structure geometry, composition and cell distribution was achieved [1]. This technology has been improved and accommodated to culture MM stem cells as part of the wide field of applicability that the method can offer for life science studies.…”

Section: Introductionmentioning

confidence: 99%

“…This generated droplet is coated by another synchronized hydrogel bead as previously reported, generating on demand three-dimensional niches for stem cell allocation by synchronizing droplet production rates. The combination of these processes of droplet generation and passive mixing without the use of external forces makes this technology suitable for the encapsulation of stem cells [1].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Droplet Microfluidics for the ex Vivo Expansion of Human Primary Multiple Myeloma Cells

et al. 2020

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We previously reported a new approach for micromanipulation and encapsulation of human stem cells using a droplet-based microfluidic device We demonstrated the possibility of encapsulating and culturing difficult-to-preserve primary human hematopoietic stem cells using an engineered double layered bead composed by an inner layer of alginate and an outer layer of puramatrix constructed using a soft technology without the use of any external force. In this work, we use this micro manipulation technique to build a 3D scaffold as a biomimetic model to recapitulate the niche of patient-derived multiple myeloma cells (MM cell) using a multilayered 3D tissue scaffold constructed in a microfluidic device and cultured in 10% FBS culture medium. In the current study, we included the use of this biomimetic model comprising supporting human Mesenchymal stem cells to show the mid-term survival of MM cells in the proposed structures. We found that the generated microniches were suitable for the maintenance of MM cells with and without supporting cells. Additionally, cultured MM cells in droplets were exposed to both Bortezomib and Lenalidomide to test their toxicity in the cultured patient derived cells. Results indicate that the maintained MM cells were consistently responding to the applied medication, opening a wide field of possibilities to use the presented micro device as an ex vivo platform for drug screening.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Droplet Microfluidics for the ex Vivo Expansion of Human Primary Multiple Myeloma Cells

et al. 2020

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“…Recently, we reported a method in which a double-layered hydrogel bead able to accommodate adult stem cells where controlled generation of the structure geometry, composition, and cell distribution was achieved [ 32 ]. We also recently described a successful technology to replicate and successfully culture ex vivo human Multiple Myeloma stem cells [ 33 ], therefore confirming the advantages of the droplet-based microfluidic platforms for the successful culture and maintenance of human primary difficult-to-culture stem cells.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Human Hematopoietic Stem Cell Culture in Microdroplets

et al. 2021

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We previously reported a new approach for micromanipulation and encapsulation of human stem cells using a droplet-based microfluidic device. This approach demonstrated the possibility of encapsulating and culturing difficult-to-preserve primary human hematopoietic stem cells using an engineered double-layered bead composed by an inner layer of alginate and an outer layer of Puramatrix. We also demonstrated the maintenance and expansion of Multiple Myeloma cells in this construction. Here, the presented microfluidic technique is applied to construct a 3D biomimetic model to recapitulate the human hematopoietic stem cell niche using double-layered hydrogel beads cultured in 10% FBS culture medium. In this model, the long-term maintenance of the number of cells and expansion of hHSCS encapsulated in the proposed structures was observed. Additionally, a phenotypic characterization of the human hematopoietic stem cells generated in the presented biomimetic model was performed in order to assess their long-term stemness maintenance. Results indicate that the ex vivo cultured human CD34+ cells from bone marrow were viable, maintained, and expanded over a time span of eight weeks. This novel long-term stem cell culture methodology could represent a novel breakthrough to improve Hematopoietic Progenitor cell Transplant (HPT) as well as a novel tool for further study of the biochemical and biophysical factors influencing stem cell behavior. This technology opens a myriad of new applications as a universal stem cell niche model potentially able to expand other types of cells.

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Microfluidic Formulation of Topological Hydrogels for Microtissue Engineering

et al. 2022

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Microfluidics has recently emerged as a powerful tool in generation of submillimeter-sized cell aggregates capable of performing tissue-specific functions, so-called microtissues, for applications in drug testing, regenerative medicine, and cell therapies. In this work, we review the most recent advances in the field, with particular focus on the formulation of cell-encapsulating microgels of small "dimensionalities": "0D" (particles), "1D" (fibers), "2D" (sheets), etc., and with nontrivial internal topologies, typically consisting of multiple compartments loaded with different types of cells and/or biopolymers. Such structures, which we refer to as topological hydrogels or topological microgels (examples including core− shell or Janus microbeads and microfibers, hollow or porous microstructures, or granular hydrogels) can be precisely tailored with high reproducibility and throughput by using microfluidics and used to provide controlled "initial conditions" for cell proliferation and maturation into functional tissue-like microstructures. Microfluidic methods of formulation of topological biomaterials have enabled significant progress in engineering of miniature tissues and organs, such as pancreas, liver, muscle, bone, heart, neural tissue, or vasculature, as well as in fabrication of tailored microenvironments for stem-cell expansion and differentiation, or in cancer modeling, including generation of vascularized tumors for personalized drug testing. We review the available microfluidic fabrication methods by exploiting various cross-linking mechanisms and various routes toward compartmentalization and critically discuss the available tissue-specific applications. Finally, we list the remaining challenges such as simplification of the microfluidic workflow for its widespread use in biomedical research, bench-to-bedside transition including production upscaling, further in vivo validation, generation of more precise organ-like models, as well as incorporation of induced pluripotent stem cells as a step toward clinical applications.

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Microengineering double layer hydrogel structures towards the recapitulation of the hematopoietic stem cell niche

Cited by 6 publications

References 15 publications

Droplet Microfluidics for the ex Vivo Expansion of Human Primary Multiple Myeloma Cells

Droplet Microfluidics for the ex Vivo Expansion of Human Primary Multiple Myeloma Cells

Long-Term Human Hematopoietic Stem Cell Culture in Microdroplets

Microfluidic Formulation of Topological Hydrogels for Microtissue Engineering

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