Biomaterial‐based notch signaling for the differentiation of hematopoietic stem cells into T cells

Taqvi, Sabia; Dixit, Lena; Roy, Krishnendu

doi:10.1002/jbm.a.31266

Cited by 17 publications

(18 citation statements)

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“…Cell-cell contact appears to be of particular importance for stem cells such as HSCs, as they form heterogeneous cell contacts with osteoblasts, adipocytes, and megakaryocytes in the endosteal niche (Table 2). To mimic T cell interactions with macrophages in vitro, HSCs have been cultured with magnetic beads conjugated to the Notch ligand delta-like ligand 4 (DLL4) to induce their differentiation into T cells (60). Furthermore, direct coculture of umbilical cord-derived HSCs with the OP9 stromal cell line engineered to express DLL1 has been shown to expand HSCs with the ability to engraft the thymus of immunodeficient mice (61).…”

Section: Engineering Stem Cell-ecm Interactions Stem Cell-ecm Interac-mentioning

confidence: 99%

Enabling stem cell therapies through synthetic stem cell–niche engineering

Peerani

Zandstra²

2010

J. Clin. Invest.

158

122

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Enabling stem cell-targeted therapies requires an understanding of how to create local microenvironments (niches) that stimulate endogenous stem cells or serve as a platform to receive and guide the integration of transplanted stem cells and their derivatives. In vivo, the stem cell niche is a complex and dynamic unit. Although components of the in vivo niche continue to be described for many stem cell systems, how these components interact to modulate stem cell fate is only beginning to be understood. Using the HSC niche as a model, we discuss here microscale engineering strategies capable of systematically examining and reconstructing individual niche components. Synthetic stem cell-niche engineering may form a new foundation for regenerative therapies.

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Section: Engineering Stem Cell-ecm Interactions Stem Cell-ecm Interac-mentioning

confidence: 99%

Enabling stem cell therapies through synthetic stem cell–niche engineering

Peerani

Zandstra²

2010

J. Clin. Invest.

158

122

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“…proteoglycans) and via steric hindrance to diffusive and advective mass transport [22][23][24][25]. Engineering approaches have explored the use of cadherin signaling to influence hematopoietic cell activity [26] and modulate autocrine feedback of monolithic HSC cultures [27]. Additionally, biomaterial design of an artificial niche offers the opportunity to regulate the transport of biomolecular signals in heterotypic cultures, and engineer HSC-generated autocrine demonstrated that the culture of HSCs microcavities as either single HSCs or pairs led to differential signaling, with autocrine feedback dominating quiescent HSC maintenance [28].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stromal cell remodeling of a gelatin hydrogel microenvironment defines an artificial hematopoietic stem cell niche

Gilchrist

Lee

et al. 2018

Preprint

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We identify a combination of an initially low-diffusivity (autocrine dominated) hydrogel and a 1:1 HSCP:MSC seeding ratio as conducive to enhanced HSC population maintenance. Further, gene expression and serial mechanical testing data suggests that MSC-mediated matrix remodeling is significant for the long-term HSC culture, reducing HSC autocrine feedback and potentially enhancing MSC-mediated paracrine signaling over 7-day culture in vitro. This work demonstrates the design of an HSC culture system that couples initial hydrogel properties, MSC co-culture, and concepts of dynamic reciprocity mediated by MSC remodeling to achieve enhanced HSC maintenance.

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“…For example, Liu et al (104) engineered "artificial niches" that incorporate the active domain of various Notch ligands for culture of NPCs. In another study, Notch ligands were coupled to magnetic microbeads by streptavidin-biotin binding and antibody-antigen coupling (150). These beads were then used to efficiently generate T cells from HSCs.…”

Section: Notch Signaling As a Main Regulator Of Cell-cell Communicationmentioning

confidence: 99%

Constructing stem cell microenvironments using bioengineering approaches

Brafman

2013

Physiological Genomics

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Within the adult organism, stem cells reside in defined anatomical microenvironments called niches. These architecturally diverse microenvironments serve to balance stem cell self-renewal and differentiation. Proper regulation of this balance is instrumental to tissue repair and homeostasis, and any imbalance can potentially lead to diseases such as cancer. Within each of these microenvironments, a myriad of chemical and physical stimuli interact in a complex (synergistic or antagonistic) manner to tightly regulate stem cell fate. The in vitro replication of these in vivo microenvironments will be necessary for the application of stem cells for disease modeling, drug discovery, and regenerative medicine purposes. However, traditional reductionist approaches have only led to the generation of cell culture methods that poorly recapitulate the in vivo microenvironment. To that end, novel engineering and systems biology approaches have allowed for the investigation of the biological and mechanical stimuli that govern stem cell fate. In this review, the application of these technologies for the dissection of stem cell microenvironments will be analyzed. Moreover, the use of these engineering approaches to construct in vitro stem cell microenvironments that precisely control stem cell fate and function will be reviewed. Finally, the emerging trend of using high-throughput, combinatorial methods for the stepwise engineering of stem cell microenvironments will be explored.

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Biomaterial‐based notch signaling for the differentiation of hematopoietic stem cells into T cells

Cited by 17 publications

References 0 publications

Enabling stem cell therapies through synthetic stem cell–niche engineering

Enabling stem cell therapies through synthetic stem cell–niche engineering

Mesenchymal stromal cell remodeling of a gelatin hydrogel microenvironment defines an artificial hematopoietic stem cell niche

Constructing stem cell microenvironments using bioengineering approaches

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