The use of covalently immobilized stem cell factor to selectively affect hematopoietic stem cell activity within a gelatin hydrogel

Mahadik, Bhushan; Haba, Sara Pedron; Skertich, Luke J.; Harley, Brendan A.C.

doi:10.1016/j.biomaterials.2015.07.042

Cited by 101 publications

(102 citation statements)

References 83 publications

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“…Here, we describe the use of estradiol and progesterone to alter the individual and combined proangiogenic activities of endometrial epithelial and stromal cells (endoEpCs and endoSCs, respectively), as well as subsequent endothelial cell vessel formation, within a methacrylamide-functionalized gelatin (GelMA) hydrogel recently described by our laboratory. [14] All experiments were performed in three-dimensions, with cells encapsulated directly within the hydrogel matrix from the start of the experiment. Inspired by the temporal presentation of sex steroids within the native endometrium, we also explore a method using sex hormone binding globulin (SHBG) to sequester estradiol within the hydrogel as a means to alter residence time.…”

Section: Introductionmentioning

confidence: 99%

Proangiogenic Activity of Endometrial Epithelial and Stromal Cells in Response to Estradiol in Gelatin Hydrogels

2017

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Biomaterial vascularization remains a major focus in the field of tissue engineering. Biomaterial culture of endometrial cells is described as a platform to inform the design of proangiogenic biomaterials. The endometrium undergoes rapid growth and shedding of dense vascular networks during each menstrual cycle mediated via estradiol and progesterone in vivo. Cocultures of endometrial epithelial and stromal cells encapsulated within a methacrylamide-functionalized gelatin hydrogel are employed. It is reported that proangiogenic gene expression profiles and vascular endothelial growth factor production are hormone dependent in endometrial epithelial cells, but that hormone signals have no effect on human telomerase reverse transcriptase (hTERT)-immortalized endometrial stromal cells. This study subsequently examines whether the magnitude of epithelial cell response is sufficient to induce changes in human umbilical vein endothelial cell network formation. Incorporation of endometrial stromal cells improves vessel formation, but co-culture with endometrial epithelial cells leads to a decrease in vascular formation, suggesting the need for stratified cocultures of endometrial epithelial and stromal cells with endothelial cells. Given the transience of hormonal signals within 3D biomaterials, the inclusion of sex hormone binding globulin (SHBG) to alter the bioavailability of estradiol within the hydrogel is reported, demonstrating a strategy to reduce diffusive losses via SHBG-mediated estradiol sequestration.

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Section: Introductionmentioning

confidence: 99%

Proangiogenic Activity of Endometrial Epithelial and Stromal Cells in Response to Estradiol in Gelatin Hydrogels

2017

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“…Primary murine Hematopoietic stem progenitor cells (HSPC) were extracted from the femur and tibia bone marrow of C57BL/6 female mice, age 4 -8 weeks (Jackson Labs). The bones were gently crushed with pestle and mortar, and washed with PBS + 5%FBS prior to filtration with a 40µm sterile filter [29,46]. The collected suspension was lysed with ACK lysis buffer (Invitrogen, Carlsbad, CA), and then rinsed with PBS/FBS.…”

Section: Hematopoietic Stem Cell Isolationmentioning

confidence: 99%

“…The LSK faction was collect in PBS + 25% FBS on ice and immediately used [19,29,46,[67][68][69][70].…”

Section: Hematopoietic Stem Cell Isolationmentioning

confidence: 99%

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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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“…Stem cell factor coupled to methacrylamide-functionalized gelatin gels (GelMA) has been used to analyze the influence on Lin − Sca-1 + c-kit + (LSK) cells with regard to maintaining more primitive HSC fractions, viability and expansion. It was shown that matrix-immobilized SCF is more selective in its ability to maintain primitive HSC fractions within a fully-3D hydrogel biomaterial as compared to soluble SCF in the media, likely due to exclusion of soluble SCFinduced differentiation [90]. A unique approach that made use of so-called inverted colloidal crystals (ICC) for the generation of polyacrylamide gels with a layer-by-layer-surface coating of DLL-1 notch ligand showed that when cultivating the mononuclear fraction, pre-erythrocytes and dendritic cells could be observed whereas when HSCs from cord blood were cultivated, T-cell lineage commitment and differentiation could be seen [91].…”

Section: Gel-based Systemsmentioning

confidence: 99%

Artificial Hematopoietic Stem Cell Niches-Dimensionality Matters

Gottwald¹

2017

ATROA

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Hematopoietic stem cell niches are perhaps the best described niche system in mammals. The niches themselves, as well as their cellular and structural constituents and factors that play a role in maintaining the niche structure and function, are being refined on a more or less daily basis. Despite this, it seems as if the more we know the harder it gets to mimic the in vivo-situation using in vitro-systems. This is due to the fact that hematopoiesis is a multi step maturation process leading to HSC heterogeneity. Subpopulations of HSCs and niche supporting cells can be defined depending on characteristics such as their potency of leading to successful reconstitution of sub lethally irradiated mice in serial transplantation experiments or, with less scientific impact, clonogenic assays. Since the bone marrow obviously provides all necessary information to maintain the stem cell pool constant and to adapt the number of blood cells according to physiologic needs, it has been the goal to engineer artificial niches that display at least one or several of the major characteristics of the in vivosituation to make use of these systems for not only fundamental research purposes but, moreover, also for clinical applications. This review will give an overview of approaches to engineering artificial hematopoietic niches with a focus on the complexity/dimensionality of the systems used.

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The use of covalently immobilized stem cell factor to selectively affect hematopoietic stem cell activity within a gelatin hydrogel

Cited by 101 publications

References 83 publications

Proangiogenic Activity of Endometrial Epithelial and Stromal Cells in Response to Estradiol in Gelatin Hydrogels

Proangiogenic Activity of Endometrial Epithelial and Stromal Cells in Response to Estradiol in Gelatin Hydrogels

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

Artificial Hematopoietic Stem Cell Niches-Dimensionality Matters

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