The effects of short-term hypoxia on human mesenchymal stem cell proliferation, viability and p16(INK4A) mRNA expression: Investigation using a simple hypoxic culture system with a deoxidizing agent

A hypoxic environment is thought to be important for the maintenance of stemness and suppressing cell senescence, in stem cells. Therefore, a hypoxic condition is induced during cell expansion and/or induction of intended differentiation. However, the induction of these conditions requires a specially equipped hypoxia chamber and expensive gas mixtures, which are expensive and space-consuming. Owing to these restrictions, appropriate hypoxic conditions cannot be provided during cell transportation, which is increasingly required for regenerative medicine. Hence, a simple and economical culture system is required. The purpose of this study was to investigate the effects of short-term hypoxic conditions on human mesenchymal stem cell (MSC) proliferation, viability, and senescence, utilizing the CulturePal system (CulturePal-Zero and CulturePal-Five), a novel and simple hypoxic culture system with a built-in deoxidizing agent. The O₂ concentration in the CulturePal-Zero was observed to reduce to <0.1% within 1 h, and to 5% within 24 h in the CulturePal-Five system. Cell proliferation under these hypoxic conditions showed a sharp increase at 5% O₂ concentration, and no noticeable cell death was observed even at severe hypoxic conditions (<0.1% O₂) up to 72h. The p16INK4A (cell senescence marker) mRNA expression was retained under hypoxic conditions up to 72h, but it was up-regulated under normoxic conditions. Interestingly, the p16INK4A expression altered proportionately to the O₂ concentration. These results indicated that the short-term hypoxic condition, at an approximate O₂ concentration of 5%, would be suitable for promoting cell proliferation and repressing cell senescence, without aggravating the MSC viability. Therefore, the CulturePal systems may be suitable for providing an appropriate hypoxic condition in stem cell research and transportation

Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture

ヒトのiPS細胞から腱の細胞を作製する --アキレス腱断裂のラットに移植し、機能回復を確認--. 京都大学プレスリリース. 2021-08-31.Repairing tendon injuries with stem cells. 京都大学プレスリリース. 2021-08-31.Tendon self-renewal is a rare occurrence because of the poor vascularization of this tissue; therefore, reconstructive surgery using autologous tendon is often performed in severe injury cases. However, the post-surgery re-injury rate is relatively high, and the collection of autologous tendons leads to muscle weakness, resulting in prolonged rehabilitation. Here, we introduce an induced pluripotent stem cell (iPSC)-based technology to develop a therapeutic option for tendon injury. First, we derived tenocytes from human iPSCs by recapitulating the normal progression of step-wise narrowing fate decisions in vertebrate embryos. We used single-cell RNA sequencing to analyze the developmental trajectory of iPSC-derived tenocytes. We demonstrated that iPSC-tenocyte grafting contributed to motor function recovery after Achilles tendon injury in rats via engraftment and paracrine effects. The biomechanical strength of regenerated tendons was comparable to that of healthy tendons. We suggest that iPSC-tenocytes will provide a therapeutic option for tendon injury

How Can Brain Learn to Control a Nonholonomic System?

Humans can often conduct both linear and nonlinear control tasks after a sufficient number of trials, even if they initially do not have sufficient knowledge about the system's dynamics and the way to control it. Theoretically, it is well known that some nonlinear systems cannot be stabilized asymptotically by any linear controllers and we have reported by an f-MRI experiment that different types of information may be involved in linear and nonlinear control tasks, respectively, from a brain function mapping point of view. In this paper, from a controllability analysis, we still show a possibility that human may use a linear control scheme for such nonlinear control tasks by switching the linear controllers with a virtual constraint. It is suggested that the proposed virtual constraint can play an important role to overcome a limitation of the linear controllers and to mimic human control behavior

Validation Study of the International Association for the Study of Lung Cancer Histologic Grading System of Invasive Lung Adenocarcinoma

[Introduction] A histologic grading system for invasive lung adenocarcinoma (ADC) has been proposed by the International Association for the Study of Lung Cancer (IASLC) Pathology Committee in June 2020. This study evaluated the prognostic value of the IASLC histologic grading system (the IASLC system) in a large Japanese cohort. [Methods] We performed comprehensive histologic subtyping using the semiquantitative estimation of five major patterns and complex glandular patterns in patients with a completely resected lung ADC and determined the histologic grade using the IASLC system. Concordance index and receiver-operating characteristic curves were used to evaluate the clinical utility of the IASLC system for recurrence and death; the comparison was performed with the architectural-pattern system (the Arch system) and the grading system on the basis of the two most predominant patterns (the Sica’s system). [Results] Of 1002 patients with invasive ADC, 235 had recurrent disease and 166 died of lung cancer. The concordance index and area under the curve of the IASLC system were 0.777 and 0.807 for recurrence and 0.767 and 0.776 for death, respectively. These were similar to those of the Arch system (0.763 and 0.796 for recurrence, 0.743 and 0.755 for death) and the Sica’s system (0.786 and 0.814 for recurrence, 0.762 and 0.773 for death). [Conclusions] We reported that the IASLC system for invasive lung ADC has prognostic significance by evaluating a large Japanese cohort. We believe that the IASLC grading system will provide physicians with better information for postsurgery treatment