Non-Invasive Imaging Modalities for Clinical Investigation in Regenerative Medicine

Haralampieva, Deana; Ametamey, Simon M.; Sulser, Tullio; Eberli, Daniel

doi:10.5772/59356

Cited by 6 publications

(3 citation statements)

References 69 publications

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“…Research towards the noninvasive imaging of autologous stem cell therapies is of high importance as both repeated biopsy and access to many organs are often not clinically feasible. Several modalities are being investigated for their applicability in cell tracking and cell metabolism read-outs [ 21 ]. While MRI has lower sensitivity compared to radionuclide-based tools and bioluminescence has poor spatial resolution, PET/CT is a system with both high sensitivity and resolution [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…Several modalities are being investigated for their applicability in cell tracking and cell metabolism read-outs [ 21 ]. While MRI has lower sensitivity compared to radionuclide-based tools and bioluminescence has poor spatial resolution, PET/CT is a system with both high sensitivity and resolution [ 21 ]. Additionally, although imaging reporter genes are available for fluorescence, bioluminescence, and MRI, only radionuclide-based reporter genes are currently investigated for use in patients [ 22 – 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma

Haralampieva

Salemi

Betzel

et al. 2018

Stem Cells International

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While many groups demonstrated new muscle tissue formation after muscle precursor cell (MPC) injection, the capacity of these cells to heal muscle damage, for example, sphincter in stress urinary incontinence, in long-term is still limited. Therefore, the first goal of our project was to optimize the functional regenerative potential of hMPC by genetic modification to overexpress human peroxisome proliferator-activated receptor gamma coactivator 1-alpha (hPGC-1α), key regulator of exercise-mediated adaptation. Moreover, we aimed at establishing a feasible methodology for noninvasive PET visualization of implanted cells and their microenvironment in muscle crush injury model. PGC-1α-bioengineered muscles showed enhanced marker expression for myogenesis (α-actinin, MyHC, and Desmin), vascularization (VEGF), neuronal (ACHE), and mitochondrial (COXIV) activity. Consistently, use of hPGC-1α_hMPCs produced significantly increased contractile force one to three weeks postinjury. PET imaging showed distinct differences in radiotracer signals ([18F]Fallypride and [11C]Raclopride (both targeting dopamine 2 receptors (D2R)) and [64Cu]NODAGA-RGD (targeting neovascularization)) between GFP_hMPCs and hD2R_hPGC-1α_hMPCs. After muscle harvesting, inflammation levels were in parallel to radiotracer uptake amount, with significantly lower uptake in hPGC-1α overexpressing samples. In summary, we facilitated early functional muscle tissue regeneration, introducing a novel approach to improve skeletal muscle regeneration. Besides successful tracking of hMPCs in muscle crush injuries, we showed that in high-inflammation areas, the specificity of radioligands might be significantly reduced, addressing a possible bottleneck of neovascularization PET imaging.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma

Haralampieva

Salemi

Betzel

et al. 2018

Stem Cells International

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“…While bioluminescence has poor spatial resolution and MRI lacks the high sensitivity of radionuclide-based tools, PET/CT is a system with both high resolution and high sensitivity (9). Imaging reporter genes are available for fluorescence imaging, bioluminescence imaging, and MRI, but only radionuclide-based reporter genes are currently being investigated for use in patients (10)(11)(12).…”

mentioning

confidence: 99%

Noninvasive PET Imaging and Tracking of Engineered Human Muscle Precursor Cells for Skeletal Muscle Tissue Engineering

et al. 2016

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Transplantation of human muscle precursor cells (hMPCs) is envisioned for the treatment of various muscle diseases. However, a feasible non-invasive tool to monitor cell survival, migration and integration into the host tissue is still missing. Methods In this study, we designed an adenoviral delivery system to genetically modify hMPCs to express a signaling-deficient form of a human dopamine D2 receptor (hD2R). The gene expression levels of the receptor were evaluated by Reverse Transcriptase Polymerase Chain Reaction (RTPCR) and infection efficiency was visualized by fluorescent microscopy. Viability, proliferation and differentiation capacity of the transduced cells were confirmed and their sustained myogenic phenotype was shown by flow cytometry analysis and fluorescent microscopy. 18F-Fallypride and 18F-FMISO, two well-established PET radioligands, were successfully synthesized and evaluated for their potential to image engineered hMPCs in a mouse model. Furthermore, biodistribution studies and autoradiography were also performed to determine the extent of signal specificity. Results To address the feasibility of the presented approach for tracking of hMPCs in an in vivo model, we first evaluated the safety of the adenoviral gene-delivery, which showed no detrimental effects on the primary human cells. Specific binding of 18F-Fallypride to hD2R_hMPCs was demonstrated in vitro, as well as in vivo, by performing autoradiography, biodistribution and PET experiments, respectively. Furthermore, 18F-FMISO uptake was evaluated at different time-points after cell inoculation in vivo, showing high signal only at the early stages. Finally, histological assessment of the harvested tissues confirmed the sustained survival of the transplanted cells at different time-points with formation of muscle tissue at the site of injection. Conclusion We here propose a signaling-deficient human D2R as a potent reporter for in vivo hMPCs PET tracking by 18F-Fallypride. This approach is a significant step forward towards a potential non-invasive tracking of hMPC_hD2R cells and bioengineered muscle tissues in the clinic.

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Imaging biomaterial-associated inflammation

Selvam

2017

Monitoring and Evaluation of Biomaterials and Their Performance in Vivo

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Non-Invasive Imaging Modalities for Clinical Investigation in Regenerative Medicine

Cited by 6 publications

References 69 publications

Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma

Injected Human Muscle Precursor Cells Overexpressing PGC-1α Enhance Functional Muscle Regeneration after Trauma

Noninvasive PET Imaging and Tracking of Engineered Human Muscle Precursor Cells for Skeletal Muscle Tissue Engineering

Imaging biomaterial-associated inflammation

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