Bioluminescence Imaging of Stem Cell-Based Therapeutics for Vascular Regeneration

Bioluminescence is a ubiquitous imaging modality for visualizing biological processes in vivo. This technique employs visible light and interfaces readily with most cell and tissue types, making it a versatile technology for preclinical studies. Here we review basic bioluminescence imaging principles, along with applications of the technology that are relevant to the medicinal chemistry community. These include noninvasive cell tracking experiments, analyses of protein function, and methods to visualize small molecule metabolites. In each section, we also discuss how bioluminescent tools have revealed insights into experimental therapies and aided drug discovery. Last, we highlight the development of new bioluminescent tools that will enable more sensitive and multi-component imaging experiments and, thus, expand our broader understanding of living systems.

show abstract

“…The versatility and user-friendly features of bioluminescence have facilitated numerous biological discoveries. [3,17,18]…”

Section: Introductionmentioning

confidence: 99%

Bioluminescence: a versatile technique for imaging cellular and molecular features

2014

View full text Add to dashboard Cite

show abstract

“…Reprogrammed from somatic cells, iPSCs offer an abundant source of autologous cells that mitigate immunogenicity and ethical concerns. [11] In a murine hindlimb ischemia model for peripheral arterial disease, hiPSC-ECs injected into the ischemic calf muscle enhanced microvessel density and improved blood reperfusion by secreting angiogenic cytokines and incorporating into expanding endogenous microvasculature. [12] The clinical adoption of hiPSC-EC therapy is currently hampered by the rapid decline of transplanted cell viability, which necessitates multiple cell administrations for sustaining therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

Avidity-controlled hydrogels for injectable co-delivery of induced pluripotent stem cell-derived endothelial cells and growth factors

Mulyasasmita

Cai

Dewi

et al. 2014

Journal of Controlled Release

Self Cite

View full text Add to dashboard Cite

To translate recent advances in induced pluripotent stem cell biology to clinical regenerative medicine therapies, new strategies to control the co-delivery of cells and growth factors are needed. Building on our previous work designing Mixing-Induced Two-Component Hydrogels (MITCH) from engineered proteins, here we develop protein-polyethylene glycol (PEG) hybrid hydrogels, MITCH-PEG, which form physical gels upon mixing for cell and growth factor co-delivery. MITCH-PEG is a mixture of C7, which is a linear, engineered protein containing seven repeats of the CC43 WW peptide domain (C), and 8-arm star-shaped PEG conjugated with either one or two repeats of a proline-rich peptide to each arm (P1 or P2, respectively). Both 20 kDa and 40 kDa star-shaped PEG were investigated, and all four PEG variants were able to undergo a sol-gel phase transition when mixed with the linear C7 protein at constant physiological conditions due to noncovalent hetero-dimerization between the C and P domains. Due to the dynamic nature of the C-P physical crosslinks, all four gels were observed to be reversibly shear-thinning and self-healing. The P2 variants exhibited higher storage moduli than the P1 variants, demonstrating the ability to tune the hydrogel bulk properties through a biomimetic peptide-avidity strategy. The 20 kDa PEG variants exhibited slower release of encapsulated vascular endothelial growth factor (VEGF), due to a decrease in hydrogel mesh size relative to the 40 kDa variants. Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) adopted a well-spread morphology within three-dimensional MITCH-PEG cultures, and MITCH-PEG provided significant protection from cell damage during ejection through a fine-gauge syringe needle. In a mouse hindlimb ischemia model of peripheral arterial disease, MITCH-PEG co-delivery of hiPSC-ECs and VEGF was found to reduce inflammation and promote muscle tissue regeneration compared to a saline control.

show abstract

“…This technique requires both genetic engineering of target stem cells to produce luciferase and intravenous injection of luciferin in the recipient. Like other indirect labeling systems, this technique allows differentiation between viable and nonviable cells and eliminates transfer into non-transplanted cells (de Almeida et al 2011;De Vocht et al 2012;Huang et al 2012).…”

Section: Blimentioning

confidence: 99%

Lost signature: progress and failures in in vivo tracking of implanted stem cells

Haar

Lavrentieva

Stahl

et al. 2015

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

Stem cell therapy as a part of regenerative medicine provides promising approaches for the treatment of injuries and diseases. The increasing use of mesenchymal stem cells in various medical treatments created the demand for long-term in vivo cell tracking methods. Therefore, it is necessary to analyze post-transplantational survival, biodistribution, and engraftment of cells. Furthermore, stem cell treatment has been discussed controversially due to possible association with tumor formation in the recipient. For therapeutic purpose, stem cells must undergo substantial manipulation such as differentiation and in vitro expansion, and this can lead to the occurrence of genetic aberrations and altered expression of both tumor suppression and carcinogenic factors. To control therapy, it is necessary to find a reliable and general method to track and identify implanted cells in the recipient. This is especially challenging for autologous transplantations, as standard fingerprinting methods cannot be applied. An optimal technique for in vivo cell monitoring does not yet exist, and its development holds several challenges: small numbers of transplanted cells, possibility of cell number quantification, minimal transfer of the contrast agent to non-transplanted cells, and no genetic modification. This review discusses most of the proposed solutions, including magnetic resonance imaging, magnetic particle imaging, positron emission tomography, single-photon emission computed tomography, and optical imaging methods. Additionally, the recent research on cell labeling for stem cell monitoring after transplantation including in vitro, ex vivo, and in vivo imaging studies is described. Promising future imaging modalities for stem cell monitoring after transplantation are shown.

show abstract

Bioluminescence Imaging of Stem Cell-Based Therapeutics for Vascular Regeneration

Cited by 32 publications

References 48 publications

Bioluminescence: a versatile technique for imaging cellular and molecular features

Bioluminescence: a versatile technique for imaging cellular and molecular features

Avidity-controlled hydrogels for injectable co-delivery of induced pluripotent stem cell-derived endothelial cells and growth factors

Lost signature: progress and failures in in vivo tracking of implanted stem cells

Contact Info

Product

Resources

About