3D models of the bone marrow in health and disease: yesterday, today, and tomorrow

Raic, Annamarija; Naolou, Toufik; Mohra, Anna; Chatterjee, Chandralekha; Lee-Thedieck, Cornelia

doi:10.1557/mrc.2018.203

Cited by 34 publications

(35 citation statements)

References 124 publications

(176 reference statements)

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“…On the other hand, alginate hydrogel Young’s modulus ranges from 100 Pa (relatively elastic) to 10 kPa (moderately stiff) [ 114 , 115 ] making it more suitable for mimicking the BM because BM Young’s modulus ranges from 0.1 to 1 kPa [ 1 ]. For example, in cultures of non-adherent abnormal cells, such as myeloblastic lineage cells, alginate provides a more realistic environment than Matrigel, retaining leukemic cells and improving their response [ 50 ].…”

Section: Resultsmentioning

confidence: 99%

“…For example, in cultures of non-adherent abnormal cells, such as myeloblastic lineage cells, alginate provides a more realistic environment than Matrigel, retaining leukemic cells and improving their response [ 50 ]. In addition, when used as an ECM, alginate hydrogel provides greater cell growth compared to standard cell culture protocols [ 1 ].…”

Section: Resultsmentioning

confidence: 99%

“…BM is responsible for producing blood, bone, and immune system cells in a process known as hematopoiesis [ 1 ]. BM is located in trabecular cavities of bones and comprises several cell types, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), osteoblasts, and other niche cells [ 2 ], and also the heterogeneous extracellular matrix (ECM) and an intricate network of blood vessels.…”

Section: Introductionmentioning

confidence: 99%

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Microfluidics and organ-on-a-chip technologies: A systematic review of the methods used to mimic bone marrow

et al. 2020

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Bone marrow (BM) is an organ responsible for crucial processes in living organs, e. g., hematopoiesis. In recent years, Organ-on-a-Chip (OoC) devices have been used to satisfy the need for in vitro systems that better mimic the phenomena occurring in the BM microenvironment. Given the growing interest in these systems and the diversity of developed devices, an integrative systematic literature review is required. We have performed this review, following the PRISMA method aiming to identify the main characteristics and assess the effectiveness of the devices that were developed to represent the BM. A search was performed in the Scopus, PubMed, Web of Science and Science Direct databases using the keywords ((“bone marrow” OR “hematopoietic stem cells” OR “haematopoietic stem cells”) AND (“organ in a” OR “lab on a chip” OR “microfluidic” OR “microfluidic*” OR (“bioreactor” AND “microfluidic*”))). Original research articles published between 2009 and 2020 were included in the review, giving a total of 21 papers. The analysis of these papers showed that their main purpose was to study BM cells biology, mimic BM niches, model pathological BM, and run drug assays. Regarding the fabrication protocols, we have observed that polydimethylsiloxane (PDMS) material and soft lithography method were the most commonly used. To reproduce the microenvironment of BM, most devices used the type I collagen and alginate. Peristaltic and syringe pumps were mostly used for device perfusion. Regarding the advantages compared to conventional methods, there were identified three groups of OoC devices: perfused 3D BM; co-cultured 3D BM; and perfused co-cultured 3D BM. Cellular behavior and mimicking their processes and responses were the mostly commonly studied parameters. The results have demonstrated the effectiveness of OoC devices for research purposes compared to conventional cell cultures. Furthermore, the devices have a wide range of applicability and the potential to be explored.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microfluidics and organ-on-a-chip technologies: A systematic review of the methods used to mimic bone marrow

et al. 2020

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“…In addition, these models could be used as a platform for expanding HSCs for transplantation. However, it is difficult to obtain a reliable BM model because of several critical technical challenges, from currently available 3D printing techniques to the possibility of precisely mimicking the different BM niches [78].…”

Section: D Hematopoietic Stem Cell Culturementioning

confidence: 99%

Traditional and Advanced Cell Cultures in Hematopoietic Stem Cell Studies

Ribeiro-Filho

Levy

Ruiz

et al. 2019

Cells

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Hematopoiesis is the main function of bone marrow. Human hematopoietic stem and progenitor cells reside in the bone marrow microenvironment, making it a hotspot for the development of hematopoietic diseases. Numerous alterations that correspond to disease progression have been identified in the bone marrow stem cell niche. Complex interactions between the bone marrow microenvironment and hematopoietic stem cells determine the balance between the proliferation, differentiation and homeostasis of the stem cell compartment. Changes in this tightly regulated network can provoke malignant transformation. However, our understanding of human hematopoiesis and the associated niche biology remains limited due to accessibility to human material and the limits of in vitro culture models. Traditional culture systems for human hematopoietic studies lack microenvironment niches, spatial marrow gradients, and dense cellularity, rendering them incapable of effectively translating marrow physiology ex vivo. This review will discuss the importance of 2D and 3D culture as a physiologically relevant system for understanding normal and abnormal hematopoiesis.

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“…MSCs have a clinical potential for use in cell therapies and tissue engineering (TE) due to their immunomodulatory potential, stromal functions and their great proliferation as well as differentiation capacities in vitro (Dominici et al, 2006 ). MSCs can be differentiated in different cell types and the potential of controlled chondrogenic and osteogenic differentiation of these cells makes them promising candidates for cartilage and bone TE, as well as for in vitro 2D and 3D models for drug screening and disease modeling (Raic et al, 2019 ). Because of rising ethical, safety and scientific concerns, the World Health Organization and Good Manufacturing Practice (GMP) guidelines recommend the prohibition of the use of animal-derived supplements or supplements containing animal-sourced ingredients for stem cell cultivations or advanced therapy medicinal products (Schrödel, 2007 ; Lindroos et al, 2009 ; Bieback, 2013 ; Gstraunthaler et al, 2013 ; Hemeda et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of Mesenchymal Stem Cell Cultivation in Fetal Calf Serum, Human Serum, and Platelet Lysate in 2D and 3D Systems

Kirsch

Rach

Handke

et al. 2021

Front. Bioeng. Biotechnol.

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In vitro two-dimensional (2D) and three-dimensional (3D) cultivation of mammalian cells requires supplementation with serum. Mesenchymal stem cells (MSCs) are widely used in clinical trials for bioregenerative medicine and in most cases, in vitro expansion and differentiation of these cells are required before application. Optimized expansion and differentiation protocols play a key role in the treatment outcome. 3D cell cultivation systems are more comparable to in vivo conditions and can provide both, more physiological MSC expansion and a better understanding of intercellular and cell-matrix interactions. Xeno-free cultivation conditions minimize risks of immune response after implantation. Human platelet lysate (hPL) appears to be a valuable alternative to widely used fetal calf serum (FCS) since no ethical issues are associated with its harvest, it contains a high concentration of growth factors and cytokines and it can be produced from expired platelet concentrate. In this study, we analyzed and compared proliferation, as well as osteogenic and chondrogenic differentiation of human adipose tissue-derived MSCs (hAD-MSC) using three different supplements: FCS, human serum (HS), and hPL in 2D. Furthermore, online monitoring of osteogenic differentiation under the influence of different supplements was performed in 2D. hPL-cultivated MSCs exhibited a higher proliferation and differentiation rate compared to HS- or FCS-cultivated cells. We demonstrated a fast and successful chondrogenic differentiation in the 2D system with the addition of hPL. Additionally, FCS, HS, and hPL were used to formulate Gelatin-methacryloyl (GelMA) hydrogels in order to evaluate the influence of the different supplements on the cell spreading and proliferation of cells growing in 3D culture. In addition, the hydrogel constructs were cultivated in media supplemented with three different supplements. In comparison to FCS and HS, the addition of hPL to GelMA hydrogels during the encapsulation of hAD-MSCs resulted in enhanced cell spreading and proliferation. This effect was promoted even further by cultivating the hydrogel constructs in hPL-supplemented media.

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3D models of the bone marrow in health and disease: yesterday, today, and tomorrow

Cited by 34 publications

References 124 publications

Microfluidics and organ-on-a-chip technologies: A systematic review of the methods used to mimic bone marrow

Microfluidics and organ-on-a-chip technologies: A systematic review of the methods used to mimic bone marrow

Traditional and Advanced Cell Cultures in Hematopoietic Stem Cell Studies

Comparative Analysis of Mesenchymal Stem Cell Cultivation in Fetal Calf Serum, Human Serum, and Platelet Lysate in 2D and 3D Systems

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