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The therapeutic potential of donor-derived mesenchymal stromal cells (MSCs) has been investigated in diverse diseases 1 , including steroid-resistant acute graft versus host disease (SR-aGvHD) 2 . However, conventional manufacturing approaches are hampered by challenges with scalability and interdonor variability, and clinical trials have shown inconsistent outcomes 3,4 . Induced pluripotent stem cells (iPSCs) have the potential to overcome these challenges, due to their capacity for multilineage differentiation and indefinite proliferation 5,6 . Nonetheless, human clinical trials of iPSC-derived cells have not previously been completed. CYP-001 (iPSC-derived MSCs) is produced using an optimized, good manufacturing practice (GMP)-compliant manufacturing process. We conducted a phase 1, open-label clinical trial (no. NCT02923375) in subjects with SR-aGvHD. Sixteen subjects were screened and sequentially assigned to cohort A or cohort B (n = 8 per group). One subject in cohort B withdrew before receiving CYP-001 and was excluded from analysis. All other subjects received intravenous infusions of CYP-001 on days 0 and 7, at a dose level of either 1 × 10 6 cells per kg body weight, to a maximum of 1 × 10 8 cells per infusion (cohort A), or 2 × 10 6 cells per kg body weight, to a maximum dose of 2 × 10 8 cells per infusion (cohort B). The primary objective was to assess the safety and tolerability of CYP-001, while the secondary objectives were to evaluate efficacy based on the proportion of participants who showed a complete response (CR), overall response (OR) and overall survival (OS) by days 28/100. CYP-001 was safe and well tolerated. No serious adverse events were assessed as related to CYP-001. OR, CR and OS rates by day 100 were 86.7, 53.3 and 86.7%, respectively. The therapeutic application of iPSC-derived MSCs may now be explored in diverse inflammatory and immune-mediated diseases.

The new NCRP Report No. 147 includes methodology to determine x-ray protective shielding for CT scanner rooms. This methodology assumes fixed values of the scatter fraction per centimeter (kappa) for the peripheral axis of the head and body CT phantoms. An investigation was performed to determine kappa for different makes and models of CT scanner and examine the consequences of the differences between these and the fixed NCRP values on a typical shielding calculation. kappa values were calculated using an equation for the scattered air kerma at 1 m from NCRP 147 (Kerma(scatter) = kappa x ScanLength x CTDI(100) x pitch(-1)) and using scattered air kerma data provided by the manufacturers and measured CTDI(100) (periphery) values. Typical barrier calculations, following NCRP 147 methodology, were performed for each CT scanner using the fixed kappa values and, separately, using the calculated scanner-specific values. Ten CT scanner models from three manufacturers were investigated. The calculated scanner-specific kappa values varied from the NCRP fixed values by as much as 82%. However, when these kappa values were used in typical barrier calculations, the final shielding requirements using the NCRP fixed values were 0.5 to 13% less than those using the scanner specific values. It is likely that such small underestimates in the shielding requirement due to using the NCRP fixed kappa values would be more than compensated by the conservative assumptions that are incorporated in a typical barrier calculation.

Both glucose administration and extracellular volume expansion augment urinary calcium and magnesium excretion. While volume expansion also augments sodium excretion, glucose induces an antinatriuresis. To examine the interrelationships of volume expansion and of glucose administration on sodium, calcium, and magnesium excretion, the effects of glucose were evaluated during clearance studies in the same subjects before and after chronic extracellular volume expansion produced by desoxycorticosterone acetate (DOCA) and a normal dietary sodium intake. The augmentation of U(Ca)V and U(Mg)V by glucose was simply additive to the increments in divalent cation excretion caused by "escape" from the sodium-retaining effects of DOCA. Glucose administration reduced U(Na)V, an effect exaggerated after DOCA escape and associated with reductions in volume/glomerular filtration rate (V/GFR) and C(Na) + C(H2O)/GFR, suggesting augmented proximal tubular reabsorption. Before glucose, U(Na) was inversely correlated with U(G), and after glucose administration C(Na)/GFR was inversely correlated with T(G)/GFR. We propose that the availability of glucose in the proximal tubule stimulates Na reabsorption while delaying development of a chloride diffusion potential, thereby inhibiting tubular reabsorption of Ca and Mg.