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Pre- and postmortem imaging of transplanted cells.

Andrzejewska A, Nowakowski A, Janowski M, Bulte JW, Gilad AA, Walczak P, Lukomska B - Int J Nanomedicine (2015)

Bottom Line: Therapeutic interventions based on the transplantation of stem and progenitor cells have garnered increasing interest.Further progress in this field is contingent upon access to techniques that facilitate an unambiguous identification and characterization of grafted cells.Following is a focused overview of the currently available cell detection and tracking methodologies that covers the entire spectrum from pre- to postmortem cell identification.

View Article: PubMed Central - PubMed

Affiliation: NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

ABSTRACT
Therapeutic interventions based on the transplantation of stem and progenitor cells have garnered increasing interest. This interest is fueled by successful preclinical studies for indications in many diseases, including the cardiovascular, central nervous, and musculoskeletal system. Further progress in this field is contingent upon access to techniques that facilitate an unambiguous identification and characterization of grafted cells. Such methods are invaluable for optimization of cell delivery, improvement of cell survival, and assessment of the functional integration of grafted cells. Following is a focused overview of the currently available cell detection and tracking methodologies that covers the entire spectrum from pre- to postmortem cell identification.

No MeSH data available.


Related in: MedlinePlus

High-resolution MRI images.Notes: Brain has two tumors, a control (wt) and a glioma expressing a recombinant MRI reporter HSV1-TK, highlighted using CEST imaging.Abbreviations: MRI, magnetic resonance imaging; HSV1-TK, herpes simplex virus type-1 thymidine kinase; CEST, chemical exchange saturation transfer; h, hour.
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f2-ijn-10-5543: High-resolution MRI images.Notes: Brain has two tumors, a control (wt) and a glioma expressing a recombinant MRI reporter HSV1-TK, highlighted using CEST imaging.Abbreviations: MRI, magnetic resonance imaging; HSV1-TK, herpes simplex virus type-1 thymidine kinase; CEST, chemical exchange saturation transfer; h, hour.

Mentions: One potential application of such reporter genes is in regenerative medicine, where cells (eg, stem, progenitors, or immune cells) are transplanted into patients to repair a damaged tissue. Since the fate of these cells after transplantation is mostly unknown, it would be greatly beneficial if the cells could be tagged. Ideally, the “tag” should be a protein or an enzyme that is expressed only in the transplanted cells and for as long as the cells are viable. Therefore, reporter genes based on CEST MRI have an advantage, since they are bioorganic and biocompatible and are constitutively and continuously expressed by the cell. The first generation of a CEST-based reporter gene was a synthetic gene that encodes a lysine-rich protein. This reporter was used to distinguish glioma cells that overexpress the transgene from control cells in vivo in an animal model.88 Along the same lines, a synthetic gene was used to encode to an artificial protein that could sense cellular signaling.89 These studies were followed by a reengineering of the human protamine 1 (hPRM-1) gene as a CEST-based reporter. Since the hPRM-1 is a human protein, which is normally only expressed in sperm cells, it has a very low background signal in the body. Moreover, this is a human protein, and, therefore, would not be expected to trigger an immune reaction. Protamine was also used to monitor sustained drug release. Recently, CEST was applied to detect the activity of the theranostic enzymes, cytosine deaminase, carboxypeptidase G2, and herpes simplex virus type-1 thymidine kinase (HSV1-TK) (Figure 2).80,90–93 In these cases, the reporter can be used both for tagging the cells, if an imaging probe is used, and also as a suicide gene if a different compound (a prodrug) is used. Thus, such a theranostic gene has an additive value, especially where cells are needed to eradicate tumors. Unlike other labeling techniques, which have a very limited selection of compounds that can be used as imaging agents, CEST MRI that relies on bioorganic compounds allows almost endless possibilities for probe selection and design. Therefore, this technology holds great promise for the next generation of diagnostic imaging tools.


Pre- and postmortem imaging of transplanted cells.

Andrzejewska A, Nowakowski A, Janowski M, Bulte JW, Gilad AA, Walczak P, Lukomska B - Int J Nanomedicine (2015)

High-resolution MRI images.Notes: Brain has two tumors, a control (wt) and a glioma expressing a recombinant MRI reporter HSV1-TK, highlighted using CEST imaging.Abbreviations: MRI, magnetic resonance imaging; HSV1-TK, herpes simplex virus type-1 thymidine kinase; CEST, chemical exchange saturation transfer; h, hour.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562754&req=5

f2-ijn-10-5543: High-resolution MRI images.Notes: Brain has two tumors, a control (wt) and a glioma expressing a recombinant MRI reporter HSV1-TK, highlighted using CEST imaging.Abbreviations: MRI, magnetic resonance imaging; HSV1-TK, herpes simplex virus type-1 thymidine kinase; CEST, chemical exchange saturation transfer; h, hour.
Mentions: One potential application of such reporter genes is in regenerative medicine, where cells (eg, stem, progenitors, or immune cells) are transplanted into patients to repair a damaged tissue. Since the fate of these cells after transplantation is mostly unknown, it would be greatly beneficial if the cells could be tagged. Ideally, the “tag” should be a protein or an enzyme that is expressed only in the transplanted cells and for as long as the cells are viable. Therefore, reporter genes based on CEST MRI have an advantage, since they are bioorganic and biocompatible and are constitutively and continuously expressed by the cell. The first generation of a CEST-based reporter gene was a synthetic gene that encodes a lysine-rich protein. This reporter was used to distinguish glioma cells that overexpress the transgene from control cells in vivo in an animal model.88 Along the same lines, a synthetic gene was used to encode to an artificial protein that could sense cellular signaling.89 These studies were followed by a reengineering of the human protamine 1 (hPRM-1) gene as a CEST-based reporter. Since the hPRM-1 is a human protein, which is normally only expressed in sperm cells, it has a very low background signal in the body. Moreover, this is a human protein, and, therefore, would not be expected to trigger an immune reaction. Protamine was also used to monitor sustained drug release. Recently, CEST was applied to detect the activity of the theranostic enzymes, cytosine deaminase, carboxypeptidase G2, and herpes simplex virus type-1 thymidine kinase (HSV1-TK) (Figure 2).80,90–93 In these cases, the reporter can be used both for tagging the cells, if an imaging probe is used, and also as a suicide gene if a different compound (a prodrug) is used. Thus, such a theranostic gene has an additive value, especially where cells are needed to eradicate tumors. Unlike other labeling techniques, which have a very limited selection of compounds that can be used as imaging agents, CEST MRI that relies on bioorganic compounds allows almost endless possibilities for probe selection and design. Therefore, this technology holds great promise for the next generation of diagnostic imaging tools.

Bottom Line: Therapeutic interventions based on the transplantation of stem and progenitor cells have garnered increasing interest.Further progress in this field is contingent upon access to techniques that facilitate an unambiguous identification and characterization of grafted cells.Following is a focused overview of the currently available cell detection and tracking methodologies that covers the entire spectrum from pre- to postmortem cell identification.

View Article: PubMed Central - PubMed

Affiliation: NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

ABSTRACT
Therapeutic interventions based on the transplantation of stem and progenitor cells have garnered increasing interest. This interest is fueled by successful preclinical studies for indications in many diseases, including the cardiovascular, central nervous, and musculoskeletal system. Further progress in this field is contingent upon access to techniques that facilitate an unambiguous identification and characterization of grafted cells. Such methods are invaluable for optimization of cell delivery, improvement of cell survival, and assessment of the functional integration of grafted cells. Following is a focused overview of the currently available cell detection and tracking methodologies that covers the entire spectrum from pre- to postmortem cell identification.

No MeSH data available.


Related in: MedlinePlus