In vivo imaging and evaluation of different biomatrices for improvement of stem cell survival

Cao, Feng; Rafie, Amir H Sadrzadeh; Abilez, Oscar J.; Wang, Haichang; Blundo, Jennifer; Pruitt, Beth L.; Zarins, Christopher K.; Wu, Joseph C.

doi:10.1002/term.55

Cited by 35 publications

(29 citation statements)

References 11 publications

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“…In addition, the shear-thinning, injectability, and self-healing properties of the MITCH materials make them attractive candidates for potential cell injection applications. Currently, we are using a dorsal subcutaneous mouse model (16) to monitor the viability and distribution of cells delivered via injection within MITCH materials.…”

Section: Discussionmentioning

confidence: 99%

“…Matrigel is a commercially available hydrogel commonly used for cell encapsulation and transplantation preclinical studies. However, because of its isolation from the basement membrane of a mouse sarcoma, Matrigel is unlikely to be approved for clinical use (16,17). These data demonstrate that the viscoelastic properties exhibited by the MITCH materials are within the appropriate range for cell encapsulation and transplantation applications.…”

Section: Microrheology and Bulk Rheology Of Protein-engineered Hydrogmentioning

confidence: 96%

“…Because these hydrogels are formed by weak, transient crosslinks, we hypothesized that they would be shear-thinning, injectable, and self-healing, which are desirable properties for potential clinical materials (10,16,17). We ejected fully formed C7:P9 and N7:P9 gels (7.5 wt %) through a 26-gauge syringe needle (commonly used for patient insulin injections) by hand into microrheology chambers.…”

Section: Microrheology and Bulk Rheology Of Protein-engineered Hydrogmentioning

confidence: 99%

“…Because cells are highly sensitive to these nonphysiological conditions, these triggers can be irreversibly detrimental to the encapsulated cells and accompanying proteins; furthermore, these environmental conditions can be difficult to reproducibly control in clinical settings (15). Current cell injection techniques can result in substantial loss of transplanted viable cells (16,17). This is important because cell viability directly correlates to the success of cell transplantation therapies (18).…”

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confidence: 99%

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Two-component protein-engineered physical hydrogels for cell encapsulation

Foo

Lee

Mulyasasmita

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

293

255

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Current protocols to encapsulate cells within physical hydrogels require substantial changes in environmental conditions (pH, temperature, or ionic strength) to initiate gelation. These conditions can be detrimental to cells and are often difficult to reproduce, therefore complicating their use in clinical settings. We report the development of a two-component, molecular-recognition gelation strategy that enables cell encapsulation without environmental triggers. Instead, the two components, which contain multiple repeats of WW and proline-rich peptide domains, undergo a sol-gel phase transition upon simple mixing and hetero-assembly of the peptide domains. We term these materials mixing-induced, two-component hydrogels. Our results demonstrate use of the WW and proline-rich domains in protein-engineered materials and expand the library of peptides successfully designed into engineered proteins. Because both of these association domains are normally found intracellularly, their molecular recognition is not disrupted by the presence of additional biomolecules in the extracellular milieu, thereby enabling reproducible encapsulation of multiple cell types, including PC-12 neuronal-like cells, human umbilical vein endothelial cells, and murine adult neural stem cells. Precise variations in the molecular-level design of the two components including (i) the frequency of repeated association domains per chain and (ii) the association energy between domains enable tailoring of the hydrogel viscoelasticity to achieve plateau shear moduli ranging from Ϸ9 to 50 Pa. Because of the transient physical crosslinks that form between association domains, these hydrogels are shear-thinning, injectable, and self-healing. Neural stem cells encapsulated in the hydrogels form stable three-dimensional cultures that continue to self-renew, differentiate, and sprout extended neurites.biomaterial ͉ cell transplantation ͉ protein engineering

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Section: Discussionmentioning

confidence: 99%

Section: Microrheology and Bulk Rheology Of Protein-engineered Hydrogmentioning

confidence: 96%

Section: Microrheology and Bulk Rheology Of Protein-engineered Hydrogmentioning

confidence: 99%

mentioning

confidence: 99%

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Two-component protein-engineered physical hydrogels for cell encapsulation

Foo

Lee

Mulyasasmita

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

293

255

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“…When injected along with human embryonic stem cell-derived cardiomyocytes into infarcted hearts of rats, matrigel substantially increased stem cell engraftment and survival in a recent study (45), suggesting that matrigel forms a scaffold capable of reducing the apoptosis (anoikis) induced by the need to detach anchorage-dependent cells from their surrounding matrix before intramyocardial injection. Using noninvasive longitudinal bioluminescence imaging, authors of another recent study (46) have shown that matrigel significantly increases long-term survival (up to 5 months) of bone marrow-derived mesenchymal stem cells injected subcutaneously into mice compared with other biomatrices, such as type 1 collagen and puramatrix, or with PBS only. Our results are in line with those of these studies.…”

Section: Molecular Imaging: Imaging Gene Expression In Human Mesenchymentioning

confidence: 99%

Imaging Gene Expression in Human Mesenchymal Stem Cells: From Small to Large Animals

Willmann¹,

Paulmurugan²,

Rodriguez-Porcel³

et al. 2009

Radiology

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Purpose:To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning. Materials and Methods:Animal protocols were approved by the Institutional Administrative Panel on Laboratory Animal Care. Transduction of human MSCs by using different doses of adenovirus that contained a cytomegalovirus (CMV) promoter driving the mutant herpes simplex virus type 1 thymidine kinase reporter gene (Ad-CMV-HSV1-sr39tk) was characterized in a cell culture. A total of 2.25 ϫ 10 6 transduced (n ϭ 5) and control nontransduced (n ϭ 5) human MSCs were injected into the myocardium of 10 rats, and reporter gene expression in human MSCs was visualized with micro-PET by using the radiotracer 9-(4-[fluorine 18]-fluoro-3-hydroxymethylbutyl)-guanine (FHBG). Different numbers of transduced human MSCs suspended in either phosphatebuffered saline (PBS) (n ϭ 4) or matrigel (n ϭ 5) were injected into the myocardium of nine swine, and gene expression was visualized with a clinical PET-CT. For analysis of cell culture experiments, linear regression analyses combined with a t test were performed. To test differences in radiotracer uptake between injected and remote myocardium in both rats and swine, one-sided paired Wilcoxon tests were performed. In swine experiments, a linear regression of radiotracer uptake ratio on the number of injected transduced human MSCs was performed.

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