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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

Imaging of SPIO-labeled autologous cord blood derived cells in a patient with global cerebral ischemia.Notes: (A) Volume rendering of MRI data of the patient’s head obtained 24 hours posttransplantation. Semiautomatic segmentation is based on pixel intensity, showing the projection of the ventricular system (green) and the distribution of the SPIO signal from the transplanted cells within the occipital horn of the right ventricle (red). Note the supine configuration of the head, corresponding to positioning during surgery. The route and trajectory of cell transplantation via the frontal horn is represented by the needle. (B) Posterior-superior view of the patient’s head, emphasizing the location of the hypointense SPIO signal from autologous cord blood-derived cells transplanted within the occipital horn. (C) T2*-weighted image with an orthogonal view centered on the cellular SPIO signal in the occipital horn (white arrowhead). (D–I) Sagittal T2*-weighted MRI scans showing a longitudinal dispersion of SPIO signal within the occipital horn (white arrowheads); (D) pretransplantation, (E) 24 hours posttransplantation (PT), (F) 7 days PT, (G) 2 months PT, (H) 4 months PT, and (I) 33 months PT.Abbreviations: SPIO, superparamagnetic iron nanoparticle; MRI, magnetic resonance imaging.
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f1-ijn-10-5543: Imaging of SPIO-labeled autologous cord blood derived cells in a patient with global cerebral ischemia.Notes: (A) Volume rendering of MRI data of the patient’s head obtained 24 hours posttransplantation. Semiautomatic segmentation is based on pixel intensity, showing the projection of the ventricular system (green) and the distribution of the SPIO signal from the transplanted cells within the occipital horn of the right ventricle (red). Note the supine configuration of the head, corresponding to positioning during surgery. The route and trajectory of cell transplantation via the frontal horn is represented by the needle. (B) Posterior-superior view of the patient’s head, emphasizing the location of the hypointense SPIO signal from autologous cord blood-derived cells transplanted within the occipital horn. (C) T2*-weighted image with an orthogonal view centered on the cellular SPIO signal in the occipital horn (white arrowhead). (D–I) Sagittal T2*-weighted MRI scans showing a longitudinal dispersion of SPIO signal within the occipital horn (white arrowheads); (D) pretransplantation, (E) 24 hours posttransplantation (PT), (F) 7 days PT, (G) 2 months PT, (H) 4 months PT, and (I) 33 months PT.Abbreviations: SPIO, superparamagnetic iron nanoparticle; MRI, magnetic resonance imaging.

Mentions: A commercially available Feraheme® (ferumoxytol, AMAG Pharmaceuticals, Waltham, MA, USA) is an iron oxide with a hydrophilic carboxydextran coat.45 The overall colloidal particle size is approximately 17–31 nm in diameter. Ferumoxytol was found to be useful in human neural stem cell tracking.46 For instance, the meso-2,3-dimercaptosuccinic acid-coated iron nanoparticles were used for efficient adipose-derived stem cell labeling, thereby increasing the spectrum of possible uses for different coating materials.47 An elegant method of simultaneous MRI and fluorescence imaging is achieved by using Molday ION Rhodamine B nanoparticles, where 50 nm magnetite-based nanocolloidals are also labeled with the fluorochrome Rhodamine B, with a 565–620 nm emission wavelength.48 A similar approach was employed in bone marrow-derived stem progenitor cells, where cells were labeled with the T2 contrast agent ferumoxide and a fluorescent tissue marker.49 Ferumoxide has also been successfully used in intraventricular delivery in the pediatric patient with global ischemia (Figure 1), and long-term observation did not reveal negative consequences.50 Microsized paramagnetic iron oxide nanoparticles are another type of MRI contrast agent, in which the diameter of nanoparticles is approximately 1 µm.51 For instance, iron nanoparticles were covered with a divinylbenzene polymer to detect the migration of bone marrow-derived stromal cells in a stroke model.52 Despite the numerous examples of its use, similar to Gd-based contrast agents, SPIO labeling does not seem to be neutral for labeled cells. SPIO-based stem cell labeling as a method is presently not FDA (US Food and Drug Administration) approved, because the molecular mechanisms of SPIO actions are not clearly understood as yet. So, there are still concerns about the uncertain side effects on cell function, as well as the possible negative influence on the fate of the labeled cells.53 For instance, labeling with SPIOs could impair functional properties like migration capacity and colony formation abilities of labeled MSCs.54 However, there are FDA-approved SPIO formulations, but each clinical application needs Institutional Review Board’s approval for specific SPIO formulation and cell type to be used. In summary, despite the fact that several different MRI contrast agents exist and safety issues are not still resolved, the most popular T2 and T1 MRI-based stem cell labeling and in vivo tracking agents are SPIOs and gadolinium oxide nanoparticles.33 There are some data that indicate that the use of dual T1 and T2 MRI contrast agents could improve cell detection accuracy.31 SPIO-based agents are the only MR contrast agents that have so far been used for clinical (stem) cell tracking.55


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)

Imaging of SPIO-labeled autologous cord blood derived cells in a patient with global cerebral ischemia.Notes: (A) Volume rendering of MRI data of the patient’s head obtained 24 hours posttransplantation. Semiautomatic segmentation is based on pixel intensity, showing the projection of the ventricular system (green) and the distribution of the SPIO signal from the transplanted cells within the occipital horn of the right ventricle (red). Note the supine configuration of the head, corresponding to positioning during surgery. The route and trajectory of cell transplantation via the frontal horn is represented by the needle. (B) Posterior-superior view of the patient’s head, emphasizing the location of the hypointense SPIO signal from autologous cord blood-derived cells transplanted within the occipital horn. (C) T2*-weighted image with an orthogonal view centered on the cellular SPIO signal in the occipital horn (white arrowhead). (D–I) Sagittal T2*-weighted MRI scans showing a longitudinal dispersion of SPIO signal within the occipital horn (white arrowheads); (D) pretransplantation, (E) 24 hours posttransplantation (PT), (F) 7 days PT, (G) 2 months PT, (H) 4 months PT, and (I) 33 months PT.Abbreviations: SPIO, superparamagnetic iron nanoparticle; MRI, magnetic resonance imaging.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
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f1-ijn-10-5543: Imaging of SPIO-labeled autologous cord blood derived cells in a patient with global cerebral ischemia.Notes: (A) Volume rendering of MRI data of the patient’s head obtained 24 hours posttransplantation. Semiautomatic segmentation is based on pixel intensity, showing the projection of the ventricular system (green) and the distribution of the SPIO signal from the transplanted cells within the occipital horn of the right ventricle (red). Note the supine configuration of the head, corresponding to positioning during surgery. The route and trajectory of cell transplantation via the frontal horn is represented by the needle. (B) Posterior-superior view of the patient’s head, emphasizing the location of the hypointense SPIO signal from autologous cord blood-derived cells transplanted within the occipital horn. (C) T2*-weighted image with an orthogonal view centered on the cellular SPIO signal in the occipital horn (white arrowhead). (D–I) Sagittal T2*-weighted MRI scans showing a longitudinal dispersion of SPIO signal within the occipital horn (white arrowheads); (D) pretransplantation, (E) 24 hours posttransplantation (PT), (F) 7 days PT, (G) 2 months PT, (H) 4 months PT, and (I) 33 months PT.Abbreviations: SPIO, superparamagnetic iron nanoparticle; MRI, magnetic resonance imaging.
Mentions: A commercially available Feraheme® (ferumoxytol, AMAG Pharmaceuticals, Waltham, MA, USA) is an iron oxide with a hydrophilic carboxydextran coat.45 The overall colloidal particle size is approximately 17–31 nm in diameter. Ferumoxytol was found to be useful in human neural stem cell tracking.46 For instance, the meso-2,3-dimercaptosuccinic acid-coated iron nanoparticles were used for efficient adipose-derived stem cell labeling, thereby increasing the spectrum of possible uses for different coating materials.47 An elegant method of simultaneous MRI and fluorescence imaging is achieved by using Molday ION Rhodamine B nanoparticles, where 50 nm magnetite-based nanocolloidals are also labeled with the fluorochrome Rhodamine B, with a 565–620 nm emission wavelength.48 A similar approach was employed in bone marrow-derived stem progenitor cells, where cells were labeled with the T2 contrast agent ferumoxide and a fluorescent tissue marker.49 Ferumoxide has also been successfully used in intraventricular delivery in the pediatric patient with global ischemia (Figure 1), and long-term observation did not reveal negative consequences.50 Microsized paramagnetic iron oxide nanoparticles are another type of MRI contrast agent, in which the diameter of nanoparticles is approximately 1 µm.51 For instance, iron nanoparticles were covered with a divinylbenzene polymer to detect the migration of bone marrow-derived stromal cells in a stroke model.52 Despite the numerous examples of its use, similar to Gd-based contrast agents, SPIO labeling does not seem to be neutral for labeled cells. SPIO-based stem cell labeling as a method is presently not FDA (US Food and Drug Administration) approved, because the molecular mechanisms of SPIO actions are not clearly understood as yet. So, there are still concerns about the uncertain side effects on cell function, as well as the possible negative influence on the fate of the labeled cells.53 For instance, labeling with SPIOs could impair functional properties like migration capacity and colony formation abilities of labeled MSCs.54 However, there are FDA-approved SPIO formulations, but each clinical application needs Institutional Review Board’s approval for specific SPIO formulation and cell type to be used. In summary, despite the fact that several different MRI contrast agents exist and safety issues are not still resolved, the most popular T2 and T1 MRI-based stem cell labeling and in vivo tracking agents are SPIOs and gadolinium oxide nanoparticles.33 There are some data that indicate that the use of dual T1 and T2 MRI contrast agents could improve cell detection accuracy.31 SPIO-based agents are the only MR contrast agents that have so far been used for clinical (stem) cell tracking.55

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