Searching for information about stem cells online in an age of artificial intelligence: How should the stem cell community respond?

Patients and their families routinely use the Internet to learn about stem cell research. What they find, is increasingly influenced by ongoing changes in how information is filtered and presented online. This article reflects on recent developments in generative artificial intelligence and how the stem cell community should respond.

Dosing Limitation for Intra-Renal Arterial Infusion of Mesenchymal Stromal Cells.

The immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) make MSC therapy a promising therapeutic strategy in kidney disease. A targeted MSC administration via the renal artery offers an efficient delivery method with limited spillover to other organs. Although local administration alleviates safety issues with MSCs in systemic circulation, it introduces new safety concerns in the kidneys. In a porcine model, we employed intra-renal arterial infusion of ten million allogenic adipose tissue-derived MSCs. In order to trigger any potential adverse events, a higher dose (hundred million MSCs) was also included. The kidney function was studied by magnetic resonance imaging after the MSC infusion and again at two weeks post-treatment. The kidneys were assessed by single kidney glomerular filtration rate (skGFR) measurements, histology and inflammation, and fibrosis-related gene expression. None of the measured parameters were affected immediately after the administration of ten million MSCs, but the administration of one hundred million MSCs induced severe adverse events. Renal perfusion was reduced immediately after MSC administration which coincided with the presence of microthrombi in the glomeruli and signs of an instant blood-mediated inflammatory reaction. At two weeks post-treatment, the kidneys that were treated with one hundred million MSCs showed reduced skGFR, signs of tissue inflammation, and glomerular and tubular damage. In conclusions, the intra-renal administration of ten million MSCs is well-tolerated by the porcine kidney. However, higher concentrations (one hundred million MSCs) caused severe kidney damage, implying that very high doses of intra-renally administered MSCs should be undertaken with caution.

Graft assessment of the ex vivo perfused porcine kidney using hyperpolarized [1-13 C]pyruvate.

PURPOSE: Normothermic perfusion is an emerging strategy for donor organ preservation and therapy, incited by the high worldwide demand for organs for transplantation. Hyperpolarized MRI and MRS using [1-13 C]pyruvate and other 13 C-labeled molecules pose a novel way to acquire highly detailed information about metabolism and function in a noninvasive manner. This study investigates the use of this methodology as a means to study and monitor the state of ex vivo perfused porcine kidneys, in the context of kidney graft preservation research. METHODS: Kidneys from four 40-kg Danish domestic pigs were perfused ex vivo with whole blood under normothermic conditions, using an MR-compatible perfusion system. Kidneys were investigated using 1 H MRI as well as hyperpolarized [1-13 C]pyruvate MRI and MRS. Using the acquired anatomical, functional and metabolic data, the state of the ex vivo perfused porcine kidney could be quantified. RESULTS: Four kidneys were successfully perfused for 120 minutes and verified using a DCE perfusion experiment. Renal metabolism was examined using hyperpolarized [1-13 C]pyruvate MRI and MRS, and displayed an apparent reduction in pyruvate turnover compared with the usual case in vivo. Perfusion and blood gas parameters were in the normal ex vivo range. CONCLUSION: This study demonstrates the ability to monitor ex vivo graft metabolism and function in a large animal model, resembling human renal physiology. The ability of hyperpolarized MRI and MRS to directly compare the metabolic state of an organ in vivo and ex vivo, in combination with the simple MR implementation of normothermic perfusion, renders this methodology a powerful future tool for graft preservation research.

Mesenchymal Stromal Cells Are Retained in the Porcine Renal Cortex Independently of Their Metabolic State After Renal Intra-Arterial Infusion.

The regenerative capacities of mesenchymal stromal cells (MSCs) make them suitable for renal regenerative therapy. The most common delivery route of MSC is through intravenous infusion, which is associated with off-target distribution. Renal intra-arterial delivery offers a targeted therapy, but limited knowledge is available regarding the fate of MSCs delivered through this route. Therefore, we studied the efficiency and tissue distribution of MSCs after renal intra-arterial delivery to a porcine renal ischemia-reperfusion model. MSCs were isolated from adipose tissue of healthy male pigs, fluorescently labeled and infused into the renal artery of female pigs. Flow cytometry allowed MSC detection and quantification in tissue and blood. In addition, quantitative polymerase chain reaction was used to trace MSCs by their Y-chromosome. During infusion, a minor number of MSCs left the kidney through the renal vein, and no MSCs were identified in arterial blood. Ischemic and healthy renal tissues were analyzed 30 min and 8 h after infusion, and 1-4 × 104 MSCs per gram of tissue were detected, predominantly, in the renal cortex, with a viability >70%. Confocal microscopy demonstrated mainly glomerular localization of MSCs, but they were also observed in the capillary network around tubuli. The infusion of heat-inactivated (HI) MSCs, which are metabolically inactive, through the renal artery showed that HI-MSCs were distributed in the kidney in a similar manner to regular MSCs, suggesting a passive retention mechanism. Long-term MSC survival was analyzed by Y-chromosome tracing, and demonstrated that a low percentage of the infused MSCs were present in the kidney 14 days after administration, while HI-MSCs were completely undetectable. In conclusion, renal intra-arterial MSC infusion limited off-target engraftment, leading to efficient MSC delivery to the kidney, most of them being cleared within 14 days. MSC retention was independent of the metabolic state of MSC, indicating a passive mechanism.

Identifying notions of environment in obesity research using a mixed-methods approach.

The recent rise of computation-based methods in social science has opened new opportunities for exploring qualitative questions through analysis of large amounts of text. This article uses a mixed-methods design that incorporates machine reading, network analysis, semantic analysis, and qualitative analysis of 414 highly cited publications on obesogenic environments between 2001 and 2015. The method produces an elaborate network map exhibiting five distinct notions of environment, all of which are currently active in the field of obesity research. The five notions are institutional, built, food, family, and bodily environments. The network map is proposed as a navigational tool both for policy actors who wish to coordinate efforts between a variety of stakeholders and for researchers who wish to understand their own research and research plans in light of different positions in the field. The final part of the article explores how the network map may also initiate a broader set of reflections on the configuration, differentiation, and coherence of the field of obesity research.

Bone mineral density in the proximal tibia and calcaneus before and after arthroscopic reconstruction of the anterior cruciate ligament.

PURPOSE: To monitor changes in bone mineral density (BMD) of the proximal tibia and the calcaneus in patients with anterior cruciate ligament (ACL) rupture before and after arthroscopic reconstruction of the ligament, related to clinical data. TYPE OF STUDY: A 2-year prospective cohort study with assessment of patient evaluation of knee performance, clinical scoring of surgical results, and measurement of BMD in the tibia and calcaneus. METHODS: Eighteen patients with a unilateral ACL rupture underwent an autogenous bone-patellar tendon-bone graft ACL reconstruction. The patients were examined before surgery and after 4, 12, and 24 months. BMD was assessed bilaterally in the proximal tibia and calcaneus using dual-photon absorptiometry and converted to a Z-score by use of BMD values from a group of healthy controls. Clinical evaluation included determination of Lysholm score, quantitative Lachman test, pivot-shift test, and the patients' self-reported highest level of activity and knee performance in sports and daily activities. RESULTS: There were significant declines in Z-score of the proximal tibia of the operated leg during the first year after surgery, whereas there was no change in the calcaneus and contralateral leg. In the lateral tibia, the Z-score was significantly lower at 24 months follow-up, compared with both controls and the noninjured side, whereas BMD of the medial tibia had returned to near normal levels. There were significant improvements in Lysholm score, highest level of activity, and knee performance in daily activities and sports. The patients' evaluation of improvement in knee performance in sports activities at 24 months follow-up was associated with an increase in Z-score of the injured leg. CONCLUSIONS: We found a partially reversible decline in BMD of the proximal tibia after arthroscopic ACL reconstruction. Improvement in knee performance in sports activities was associated with an increase in BMD of the injured leg. BMD of the calcaneus remained unaffected in both legs. LEVEL OF EVIDENCE: Level III, therapeutic case control study.