Background Organ transplantation is predicted to increase as life expectancy and the incidence of chronic diseases rises. Regenerative medicine‐inspired technologies challenge the efficacy of the current allograft transplantation model. Methods A literature review was conducted using the PubMed interface of MEDLINE from the National Library of Medicine. Results were examined for relevance to innovations of organ bioengineering to inform analysis of advances in regenerative medicine affecting organ transplantation. Data reports from the Scientific Registry of Transplant Recipient and Organ Procurement Transplantation Network from 2008 to 2019 of kidney, pancreas, liver, heart, lung and intestine transplants performed, and patients currently on waiting lists for respective organs, were reviewed to demonstrate the shortage and need for transplantable organs. Results Regenerative medicine technologies aim to repair and regenerate poorly functioning organs. One goal is to achieve an immunosuppression‐free state to improve quality of life, reduce complications and toxicities, and eliminate the cost of lifelong antirejection therapy. Innovative strategies include decellularization to fabricate acellular scaffolds that will be used as a template for organ manufacturing, three‐dimensional printing and interspecies blastocyst complementation. Induced pluripotent stem cells are an innovation in stem cell technology which mitigate both the ethical concerns associated with embryonic stem cells and the limitation of other progenitor cells, which lack pluripotency. Regenerative medicine technologies hold promise in a wide array of fields and applications, such as promoting regeneration of native cell lines, growth of new tissue or organs, modelling of disease states, and augmenting the viability of existing ex vivo transplanted organs. Conclusion The future of organ bioengineering relies on furthering understanding of organogenesis, in vivo regeneration, regenerative immunology and long‐term monitoring of implanted bioengineered organs.
The interior of cells is a highly complex medium, containing numerous organelles, a matrix of different fibers and a viscous, aqueous fluid of proteins and small molecules. The interior of cells is also a highly dynamic medium, in which many components move, either by active transport or passive diffusion. The mobility and localization of proteins inside cells can provide important insights into protein function and also general cellular properties, such as viscosity. Neoplastic transformation affects numerous cellular properties, and our goal was to investigate the diffusional and binding behavior of the important mismatch repair (MMR) protein MSH2 in live human cells at various stages of neoplastic transformation. Toward this end, noncancerous, immortal, tumorigenic, and metastatic mammary epithelial cells were transfected with EGFP and EGFP-tagged MSH2. MSH2 forms two MMR proteins (MutSα and MutSβ) and we assume MSH2 is in the complex MutSα, though our results are similar in either case. Unlike the MutS complexes that bind to nuclear DNA, EGFP diffuses freely. EGFP and MutSα-EGFP diffusion coefficients were determined in the cytoplasm and nucleus of each cell type using fluorescence recovery after photobleaching. Diffusion coefficients were 14–24 μm2/s for EGFP and 3–7 μm2/s for MutSα-EGFP. EGFP diffusion increased in going from noncancerous to immortal cells, indicating a decrease in viscosity, with smaller changes in subsequent stages. MutSα produces an effective diffusion coefficient that, coupled with the free EGFP diffusion measurements, can be used to extract a pure diffusion coefficient and a pseudo-equilibrium constant K*. The MutSα nuclear K* increased sixfold in the first stage of cancer and then decreased in the more advanced stages. The ratio of nuclear to cytoplasmic K*for MutSα increased almost two orders of magnitude in going from noncancerous to immortal cells, suggesting that this quantity may be a sensitive metric for recognizing the onset of cancer.
Background and objectives: This study analyzed persistent opioid use in opioidnaïve and nonopioid-naïve patients undergoing hepatectomy for neoplastic disease.Methods: A retrospective review was performed of a prospective database using inclusion criteria of hepatectomy for neoplastic disease from October 2013 to December 2017. Prescription data were collected from the North Carolina Controlled Substance Reporting System. Persistent opioid use was defined as patients who continued filling opioid prescriptions 90 days to 1 year after surgery. Patients who did not receive opioid prescriptions between 12 months and 31 days before surgery were defined as naïve.Results: The analysis included 75 surgeries on naïve and 58 surgeries on nonnaïve patients. 56% of naïve patients and 79% of nonnaïve patients developed persistent opioid use, respectively (p = .0056). Naïve patients received 2.24 ± 4.30 MMEs/day, while nonnaïve patients received 5.50 ± 5.98 MMEs/day during Postoperative days 90-360 (95% CI, 1.41-5.10; p < .001). Naïve patients with a lower Preoperative ECOG score were more likely to develop persistent opioid use (OR, 0.45; 95% CI, 0.21-0.99; p = .048). Conclusion:More than half of naïve patients undergoing hepatectomy developed persistent opioid use within the first year, though significantly less than nonnaïve patients. Improved performance status was associated with an increased risk of persistent opioid use in naïve patients.
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