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BackgroundAs the prevalence of therapeutic approaches involving transplanted cells increases, so does the need to noninvasively track the cells to determine their homing patterns. Of particular interest is the fate of transplanted embryonic stem cell-derived hematopoietic progenitor cells (HPCs) used to restore the bone marrow pool following sublethal myeloablative irradiation. The early homing patterns of cell engraftment are not well understood at this time. Until now, longitudinal studies were hindered by the necessity to sacrifice several mice at various time points of study, with samples of the population of lymphoid compartments subsequently analyzed by flow cytometry or fluorescence microscopy. Thus, long-term study and serial analysis of the transplanted cells within the same animal was cumbersome, making difficult an accurate documentation of engraftment, functionality, and cell reconstitution patterns.MethodsHere, we devised a noninvasive, nontoxic modality for tracking early HPC homing patterns in the same mice longitudinally over a period of 9 days using mesoporous silica nanoparticles (MSNs) and magnetic resonance imaging.ResultsThis approach of potential translational importance helps to demonstrate efficient uptake of MSNs by the HPCs as well as retention of MSN labeling in vivo as the cells were traced through various organs, such as the spleen, bone marrow, and kidney. Altogether, early detection of the whereabouts and engraftment of transplanted stem cells may be important to the overall outcome. To accomplish this, there is a need for the development of new noninvasive tools.ConclusionsOur data suggest that multifunctional MSNs can label viably blood-borne HPCs and may help document the distribution and homing in the host followed by successful reconstitution.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0944-8) contains supplementary material, which is available to authorized users.

Key Points Human iPSCs differentiate into CD34+ HPCs. iPSC-derived HPCs induce T-cell anergy.

Type 1 diabetes (T1D) can be managed by transplanting either the whole pancreas or isolated pancreatic islets. However, cadaveric pancreas is scarcely available for clinical use, limiting this approach. As such, there is a great need to identify alternative sources of clinically usable pancreatic tissues. Here, we used induced pluripotent stem (iPS) cells derived from patients with T1D to generate glucose-responsive, insulin-producing cells (IPCs) via 3D culture. Initially, T1D iPS cells were resistant to differentiation, but transient demethylation treatment significantly enhanced IPC yield. The cells responded to high-glucose stimulation by secreting insulin The shape, size, and number of their granules, as observed by transmission electron microscopy, were identical to those found in cadaveric β cells. When the IPCs were transplanted into immunodeficient mice that had developed streptozotocin-induced diabetes, they promoted a dramatic decrease in hyperglycemia, causing the mice to become normoglycemic within 28 days. None of the mice died or developed teratomas. Because the cells are derived from "self," immunosuppression is not required, providing a much safer and reliable treatment option for T1D patients. Moreover, these cells can be used for drug screening, thereby accelerating drug discovery. In conclusion, our approach eliminates the need for cadaveric pancreatic tissue.

Atezolizumab plus bevacizumab has become frontline therapy for unresectable HCC. The compatibility of atezolizumab/bevacizumab with liver-directed RT has not been reported. Methods: HCC patients treated with liver-directed RT and atezolizumab/bevacizumab between 1/2020–11/2021 were included. Toxicity and outcomes were retrospectively recorded. For ALCs, we matched the analysis to a previously cohort of RT-treated HCC patients who did not receive atezolizumab/bevacizumab. Survival and time-to-liver-failure were analyzed using Kaplan–Meier. Results: Of 21 patients, with a median follow-up of 9.5 months, the median OS was 16.1 months. Post-RT, all patients had reduced tumors or treatment response. There were no ≥Grade 3 RT-related toxicities. Autoimmune complications occurred in two patients (9.5%), and GI bleeding in three patients (14.3%). Liver function remained stable post-RT. There was a marked decrease in ALCs immediately post-RT (post-RT/pre-RT ratio 47.3%, p < 0.0001), restored by 1 month to pre-treatment baseline (1-month post-RT/pre-RT ratio 95.1%, n.s.). Compared to HCC patients treated with RT alone, post-RT ALC recovery was faster with atezolizumab/bevacizumab (p = 0.009). Conclusion: In this first reported experience of RT with modern systemic therapy for HCC, combination therapy is safe and well-tolerated. As a favorable prognosticator, there appears to be faster recovery of ALC among patients who received RT with atezolizumab/bevacizumab.

Type I diabetes (T1D) is a chronic autoimmune disease caused by pancreatic β-cell destruction induced by autoantibodies and autoreactive T cells. After significant reduction of the β-cell mass, diabetes sets in and can cause significant complications. It is estimated that more than 3 million Americans have T1D, and its prevalence among young individuals is progressively rising; however, the reasons for this increase are not known. Islet transplantation is recognized as the ultimate cure for T1D, but unfortunately, the severe scarcity of available islets makes it necessary to establish alternative sources of β-cells. Our lab seeks to establish human-induced pluripotent stem cells as an unlimited, novel source of insulin-producing cells (IPCs) that are patient-specific, obviating the requirement for immunosuppression. Although several reports have emerged demonstrating successful derivation of IPCs from human pluripotent stem cells, the efficiencies of derivation are inadequate and these IPCs do not respond to glucose stimulation in vitro. We reasoned that the use of a growth factor sequestering bioscaffold and promotion of cell-cell signaling through 3D clustering would enhance the generation of functionally superior IPCs compared to those derived by 2D differentiation. Here, we discuss a novel 3D platform for the generation of highly efficient human IPCs.

PURPOSE: Cervical cancer (CC) disproportionately affects minorities who have higher incidence and mortality rates. Standard of care for locally advanced CC involves a multimodality approach including brachytherapy (BT), which independently improves oncologic outcomes. Here, we examine the impact of insurance status and race on BT utilization with the SEER database. MATERIALS AND METHODS: In total, 7,266 patients with stage I-IV CC diagnosed from 2007 to 2015 were included. BT utilization, overall survival (OS), and disease-specific survival (DSS) were compared. RESULTS: Overall, 3,832 (52.7%) received combined external beam radiation therapy (EBRT) + BT, whereas 3,434 (47.3%) received EBRT alone. On multivariate logistic regression analysis, increasing age (OR, 0.98; 95% CI, 0.98 to 0.99; P < .001); Medicaid (OR, 0.80; 95% CI, 0.72 to 0.88; P < .001), uninsured (OR, 0.67; 95% CI, 0.56 to 0.80; P < .001), and unknown versus private insurance (OR, 0.61; 95% CI, 0.43 to 0.86; P < .001); Black (OR, 0.68; 95% CI, 0.60 to 0.77; P < .001) and unknown versus White race (OR, 0.30; 95% CI, 0.13 to 0.77; P = .047); and American Joint Committee on Cancer stage II (OR, 1.07; 95% CI, 0.93 to 1.24; P = .36), stage III (OR, 0.82; 95% CI, 0.71 to 0.94; P = .006), stage IV (OR, 0.30; 95% CI, 0.23 to 0.40; P < .001), and unknown stage versus stage I (OR, 0.36; 95% CI, 0.28 to 0.45; P < .001) were associated with decreased BT utilization. When comparing racial survival differences, the 5-year OS was 44.2% versus 50.9% ( P < .0001) and the 5-year DSS was 55.6% versus 60.5% ( P < .0001) for Black and White patients, respectively. Importantly, the racial survival disparities resolved when examining patients who received combined EBRT + BT, with the 5-year OS of 57.3% versus 58.5% ( P = .24) and the 5-year DSS of 66.3% versus 66.6% ( P = .53) for Black and White patients, respectively. CONCLUSION: This work demonstrates notable inequities in BT utilization for CC that particularly affects patients of lower insurance status and Black race, which translates into inferior oncologic outcomes. Importantly, the use of BT was able to overcome racial survival differences, thus highlighting its essential value.

BACKGROUND: Intensity-modulated proton therapy (IMPT) demonstrates superior dose distribution over volumetric-modulated arc therapy (VMAT) for sparing organs-at-risk (OARs) in ipsilateral radiotherapy. To determine a clinical benefit, assessment of patient-reported outcomes (PRO) and physicianreported toxicities alongside a dosimetric analysis is needed. METHODS:Plans were analyzed for dosimetric differences. PROs were compared for patients undergoing ipsilateral curative-intent radiotherapy for tonsil and salivary gland cancers with VMAT or IMPT from 2015 to 2020. Physicianreported toxicities were compared. RESULTS: In 40 patients, IMPT was associated with decreased dose to multiple OARs and less deterioration in the following PROs: pain, swallowing function, dry mouth, sticky saliva, sensory change, cough, speech, feeling ill, and social eating. Physician-reported toxicities demonstrated less oral pain.CONCLUSION: IMPT is associated with decreased dose to OARs and less patient-reported acute deterioration in multiple head and neck domains. A strong consideration for IMPT in ipsilateral head and neck patients with cancer is warranted.head and neck cancer, IMPT, ipsilateral neck radiotherapy, proton radiotherapy, tonsil and salivary cancer 1 | INTRODUCTION Radiotherapy (RT) with or without concomitant radiosensitizing chemotherapy is utilized in the definitive and adjuvant treatment of head and neck malignancies. Curative-intent treatment of common head and neck malignancies often requires conventionally fractionated doses of 60 Gray (Gy) or more, which exposes