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Controlled delivery and minimally invasive imaging of stem cells in the lung.

ABSTRACT: Intratracheal delivery of stem cells into injured or diseased lungs can provide a variety of therapeutic and immunomodulatory effects for the treatment of acute lung injury and chronic lung disease. While the efficacy of this approach depends on delivering the proper cell dosage into the target region of the airway, tracking and analysis of the cells have been challenging, largely due to the limited understanding of cell transport and lack of suitable cell monitoring techniques. We report on the transport and deposition of intratracheally delivered stem cells as well as strategies to modulate the number of cells (e.g., dose), topographic distribution, and region-specific delivery in small (rodent) and large (porcine and human) lungs. We also developed minimally invasive imaging techniques for real-time monitoring of intratracheally delivered cells. We propose that this approach can facilitate the implementation of patient-specific cells and lead to enhanced clinical outcomes in the treatment of lung disease with cell-based therapies.

SUBMITTER: Kim J

PROVIDER: S-EPMC5638808 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

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Controlled delivery and minimally invasive imaging of stem cells in the lung.

Kim Jinho J Guenthart Brandon B O'Neill John D JD Dorrello N Valerio NV Bacchetta Matthew M Vunjak-Novakovic Gordana G

Scientific reports 20171012 1

Intratracheal delivery of stem cells into injured or diseased lungs can provide a variety of therapeutic and immunomodulatory effects for the treatment of acute lung injury and chronic lung disease. While the efficacy of this approach depends on delivering the proper cell dosage into the target region of the airway, tracking and analysis of the cells have been challenging, largely due to the limited understanding of cell transport and lack of suitable cell monitoring techniques. We report on the ...[more]

PMID: 29026127

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Project description:Despite developments in pulmonary radiotherapy, radiation-induced lung toxicity remains a problem. More sensitive lung imaging able to increase the accuracy of diagnosis and radiotherapy may help reduce this problem. Super-paramagnetic iron oxide nanoparticles are used in imaging, but without further modification can cause unwanted toxicity and inflammation. Complex carbohydrate and polymer-based coatings have been used, but simpler compounds may provide additional benefits. Herein, we designed and generated super-paramagnetic iron oxide nanoparticles coated with the neutral natural dietary amino acid glycine (GSPIONs), to support non-invasive lung imaging and determined particle biodistribution, as well as understanding the impact of the interaction of these nanoparticles with lung immune cells. These GSPIONs were characterized to be crystalline, colloidally stable, with a size of 12 ± 5 nm and a hydrodynamic diameter of 84.19 ± 18 nm. Carbon, Hydrogen, Nitrogen (CHN) elemental analysis estimated approximately 20.2 × 103 glycine molecules present per nanoparticle. We demonstrated that it is possible to determine the biodistribution of the GSPIONs in the lung using three-dimensional (3D) ultra-short echo time magnetic resonance imaging. The GSPIONs were found to be taken up selectively by alveolar macrophages and neutrophils in the lung. In addition, the GSPIONs did not cause changes to airway resistance or induce inflammatory cytokines. Alveolar macrophages and neutrophils are critical regulators of pulmonary inflammatory diseases, including allergies, infections, asthma and chronic obstructive pulmonary disease (COPD). Therefore, pulmonary Magnetic Resonance (MR) imaging and preferential targeting of these lung resident cells by our nanoparticles offer precise imaging tools, which can be utilized to develop precision targeted radiotherapy as well as diagnostic tools for lung cancer, thereby having the potential to reduce the pulmonary complications of radiation.

Project description:BackgroundComplete pulmonary metastasectomy for sarcoma metastases provides patients an opportunity for long-term survival and possible cure. Intraoperative localization of preoperatively identified metastases and identification of occult lesions can be challenging. In this trial, we evaluated the efficacy of near-infrared (NIR) intraoperative imaging using second window indocyanine green during metastasectomy to identify known metastases and to detect occult nodules.MethodsThirty patients with pulmonary nodules suspicious for sarcoma metastases were enrolled in an open-label, feasibility study (NCT02280954). All patients received intravenous indocyanine green (5 mg/kg) 24 hours before metastasectomy. Patients 1 through 10 (cohort 1) underwent metastasectomy via thoracotomy to assess fluorescence patterns of nodules detected by traditional methods (preoperative imaging and intraoperative visualization/bimanual palpation). After confirming reliability within cohort 1, patients 11 through 30 (cohort 2) underwent video-assisted thoracic surgery metastasectomy with NIR imaging.ResultsIn cohort 1, 14 out of 16 preoperatively identified pulmonary metastases (87.5%) displayed tumor fluorescence. Nonfluorescent metastases were deeper than fluorescent metastases (2.1 cm vs 1.3 cm; P = .03). Five out of 5 metastases identified during thoracotomy displayed fluorescence. NIR imaging identified 3 additional occult lesions in this cohort. In cohort 2, 33 out of 37 known pulmonary metastases (89.1%) displayed fluorescence. Nonfluorescent tumors were deeper than 2.0 cm (P = .007). NIR imaging identified 24 additional occult lesions. Of 24 occult lesions, 21 (87.5%) were confirmed metastases and the remaining 3 nodules were lymphoid aggregates.ConclusionsNIR intraoperative imaging with indocyanine green (5 mg/kg and 24 hours before surgery) localizes known sarcoma pulmonary metastases and identifies otherwise occult lesions. This approach may be a useful intraoperative adjunct to improve metastasectomy.

Dataset Information

Controlled delivery and minimally invasive imaging of stem cells in the lung.

Publications

Controlled delivery and minimally invasive imaging of stem cells in the lung.

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