Background As mesenchymal stem cells (MSCs) induce proliferation and differentiation of c-kit+ cardiac stem cells (CSCs) in vivo and in vitro, we hypothesized that combining human (h)MSCs with c-kit+ hCSCs produces greater infarct size reduction compared to either cell administered alone after MI. Methods and Results Yorkshire swine underwent balloon occlusion of the LAD coronary artery followed by reperfusion, and were immunosuppressed after MI with cyclosporine and methylprednisolone. Intramyocardial injection of either: combination hCSCs/hMSCs (1M/200M, n=5), hCSCs alone (1M, n=5), hMSCs alone (200M, n=5), or placebo (PBS, n=5) was administered to the infarct border zones at 14 days post-MI. Phenotypic response to cell therapy was assessed by cardiac MRI and micromanometer conductance catheterization hemodynamics. While each cell therapy group had reduced MI size relative to placebo (p<0.05), the MI size reduction was 2-fold greater in combination vs. either cell therapy alone (p<0.05). Accompanying enhanced MI size reduction was substantial improvement in LV chamber compliance (end-diastolic pressure volume relationship, p<0.01) and contractility (preload recruitable stroke work and dP/dtmax, p<0.05) in combination treated swine. EF was restored to baseline in cell treated pigs, while placebo pigs had persistently depressed LV function (p<0.05). Immunohistochemistry showed 7-fold enhanced engraftment of stem cells in the combination therapy group vs. either cell type alone (P<0.001). Conclusions Combining hMSCs and hCSCs as a cell therapeutic enhances scar size reduction, and restores diastolic and systolic function toward normal after MI. Taken together these findings illustrate important biological interactions between c-kit+ CSCs and MSCs that enhance cell-based therapeutic responses.

In vivo detection of transplanted stem cells is requisite for improving stem cell-based treatments by developing a thorough understanding of their therapeutic mechanisms. MRI tracking of magnetically labeled cells is non-invasive and is suitable for longitudinal studies. Molday ION Rhodamine-B™ (MIRB) is a new superparamagnetic iron oxide (SPIO) contrast agent specifically formulated for cell labeling and is readily internalized by non-phagocytic cells. This investigation characterizes mesenchymal stem cell (MSC) labeling and MR imaging properties of this new SPIO agent. Effects of MIRB on MSC viability and differentiation as well as cellular loading properties were assessed for MSC labeled with MIRB at concentrations from 5 to 100 μg Fe/ml. Labeled MSC were evaluated, in vitro, on a clinical 1.5 T MRI. Optimal scanning sequences and imaging parameters were determined based on contrast-to-noise ratio and contrast modulation. Relaxation rates (1/T2*) for gradient-echo sequences were approximated and an idealized limit of detection was established. MIRB labeling did not affect MSC viability or the ability to differentiate into either bone or fat. Labeling efficiency was found to be approximately 95% for labeling concentrations at or above 20 μg Fe/ml. Average MIRB per MSC ranged from 0.7 pg Fe for labeling MIRB concentration of 5 μg Fe/ml and asymptotically approached a value of 20–25 pg Fe/MSC as labeling concentration increased to 100 μg Fe/ml. MRI analysis of MIRB MSC revealed long echo time, gradient echo sequences to provide the most sensitivity. Limit of detection for gradient echo sequences was determined to be less than 1000 MSC, with approximately 15 pg Fe/MSC (labeled at 20μg Fe/ml). These investigations have laid the groundwork and established feasibility for the use of this contrast agent for in vivo MRI detection of MSC. Properties evaluated in this study will be used as a reference for tracking labeled MSC for in vivo studies.

Umbilical cord cysts warrant evaluation for structural defects and chromosomal anomalies such as trisomy 18, depending on the type of cyst. The appearance of an enlarged or "gigantic" cord has particular association with a patent urachus, often requiring operative exploration to repair the associated urachal remnant. We describe the unusual case of an umbilical cord cyst-measuring 9 cm in maximal diameter and comprising histopathological features of an urachalcyst-presenting in a healthy ex-36 week newborn with no associated anomalies.

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MRI-targeted biopsy of the prostate appears to have the potential to reduce the high rates of underdiagnosis and overdiagnosis associated with the current diagnostic standard of transrectal ultrasound guided systematic biopsy. Direct or “in bore” MRI-guided biopsy is one of the three methods for MRI-targeted core needle sampling of suspicious, generally Pi-RADS 4 or 5, foci within the prostate, and our early experience suggests the approach demonstrates substantial utility and promise in the care of patients with prostate cancer. We performed direct MRI-guided biopsies in 50 patients within 19 months of establishing the first referral center for this service in our region. Our preliminary results indicate the service can be easily grown due to unmet demand, primarily in patients with a negative traditional systematic biopsy but with a concerning focus at MRI (30 of 50; 60%). Other applications include evaluation of patients who are on active surveillance (n=14; ten upgraded to higher Gleason score at MRI-guided biopsy), who are biopsy naïve (n=5; all positive at MRI-guided biopsy), or post focal therapy (n=1; positive for recurrent tumor at MRI-guided biopsy). With careful patient selection and technique, we have achieved a favorable overall positive biopsy rate of 73% (37 of 50), with 84% (31 of 37) positive biopsies demonstrating Gleason score 7 or greater disease. Large multicenter comparative trials will be required to determine the relative accuracy and appropriate utilization of direct MRI guided biopsy in the care pathway of patients with known or suspected prostate cancer.