Biology subjects

Yokoo, T.

Publications and source records attributed to Yokoo, T..

4 recordsLinked to original sources

bioRxiv2024

Fetal Kidney Transplantation for In Utero Fetuses

Potter sequence, characterized by bilateral renal agenesis, oligohydramnios, and consequent pulmonary hypoplasia, presents a significant challenge in the management of affected neonates. Due to their prematurity and associated abdominal complications, these infants often fail to reach a stage where dialysis can be safely initiated and sustained, leading to an exceedingly high mortality rate. Therefore, there is hopeful anticipation that interventions serving as a bridge to achieve a state where dialysis can be safely performed will markedly improve life expectancy. We have developed a unique approach of "transplantation of fetal kidneys from a different species during the fetal period" as a bridge therapy until stable dialysis therapy can be implemented. This is a new concept of fetal therapy, targeting the fetus in utero and utilizing fetal kidneys of an appropriate size for transplantation. In this study, we first validated the approach using allogeneic transplantation. Fetal kidneys with bladders from GFP-expressing rats (gestational age 14.0-16.5 days) were transplanted subcutaneously into allogeneic rat fetuses in utero (gestational age 18.0-18.5 days) using a special needle transuterinally, and live pups were successfully obtained. The transplanted fetal kidneys with bladders were confirmed to have urine production capability. By periodic aspiration of the subcutaneous urinary cyst after birth, urine produced by the transplanted fetal kidney was successfully drained outside the body for an extended period (up to 150 days). Biochemical tests confirmed the solute removal capacity of the transplanted fetal kidney. Furthermore, despite allogeneic transplantation, long-term urine production was sustained without the use of immunosuppressants, confirming that organ transplantation into fetuses is associated with lower rejection compared to adult transplantation. Next, xenotransplantation was performed. When GFP-expressing mouse fetal kidneys (gestational age 13.0-13.5 days) were transplanted into rat fetuses in utero, maturation of renal tissue structures was confirmed even in the interspecies setting.

bioengineering↗

bioRxiv2024

Generation of human-pig chimeric renal organoids using iPSC technology

The potential of using porcine organs and human induced pluripotent stem cell (iPSC)-derived organoids as alternative organs for human transplantation has garnered growing attention. However, both approaches still face technological challenges. Interspecies chimeric organ production using human iPSCs is expected to be another promising approach that addresses the challenges associated with organ production. Our research group successfully generated human-mouse chimeric renal organoids by utilizing human iPSC-derived nephron progenitor cells (NPCs) and fetal mouse kidneys. However, the current technology has limited engraftment and development capabilities for human NPCs, and there have been no reports of generating interspecies chimeric renal organoids in larger animals, limited only to rodents. Therefore, in this study, we embarked on the production of human-pig chimeric renal organoids using the pig kidney, which is considered the most promising source of organs for interspecies transplantation to humans. To construct a human-pig chimeric renal organoid culture system, we first modified the existing human-mouse chimeric renal organoid culture system and developed a method that enables the survival and continued renal development of both species. This method was found to be applicable to porcine fetal kidney cells, and ultimately, we successfully produced human-pig chimeric renal organoids. Furthermore, this culture method can also be applied to the generation of human interspecies chimeric kidneys for future clinical applications. The findings of this study serve as a foundational technology that will greatly accelerate future research in humanized pig kidney production for clinical purposes, and are also expected to be used as an evaluation technique to ensure the quality of human NPCs for xenotransplantation.

bioengineering↗

bioRxiv2020

Reconstruction of the urinary tract at the appropriate time reduces fibrosis of the metanephros in rats as judged by imaging

Chronic kidney disease leads to high morbidity rates among humans. It is a serious disease that requires curative treatments other than kidney transplantation. Recently, we successfully established the iPS-derived generated kidney, which might produce urine. The urine can be directed to the native bladder with a stepwise peristaltic ureter system, followed by anastomosis with the recipient ureter for reconstruction of the urinary tract. However, the growth of the regenerated kidney varies significantly, whereas the time window of the anastomosis is quite narrow. Therefore, this study was conducted to evaluate the growth of transplanted metanephros with bladder periodically and noninvasively using computed tomography and ultrasonography. Ultrasonographic findings showed high correlations with computed tomographic findings and clearly evaluated metanephros with bladder. We found that the degree of growth of the metanephros with bladder after the transplantation differed in each individual. However, most of them reached the appropriate period for urinary tract reconstruction within 3 weeks after transplantation. Optimizing the stepwise peristaltic ureter system anastomosis by ultrasonography reduced long-term tubular dilation of the metanephros, thereby decreasing fibrosis caused by transforming growth factor-{beta}. This may be significantly related to long-term maturation of fetal grafts. These results provide new insights into transplanting regenerated kidneys in higher animals. We are one step closer to the first human trial of kidney generation.

developmental biology↗

bioRxiv2019

A slight decrease in serum albumin level is associated with rapid progression of kidney dysfunction even within the normal range: The Yuport Health Checkup Center Cohort Study

ObjectiveA low-normal albumin level is associated with a high risk of cardiovascular disease and mortality in the general population. However, the relationship between serum albumin level and future decline of kidney function is unclear. We aimed to clarify the effect of serum albumin level on the decline of kidney function in the general population.\n\nMethodsThe data used were from 11,000 participants of a voluntary health checkup program between 1998 and 2006 conducted in Japan. The primary outcome for kidney function was a difference in estimated glomerular filtration rate ({Delta}eGFR) of [≥]3 mL/min/1.73 m2/year. The association of the risk of decreased kidney function with albumin level was determined using a logistic regression analysis. We fit separate multivariable logistic regressions for serum albumin levels (g/dL) as a continuous variable and as categorical data, classified as [≤]4.3 (n=2,530), 4.4- 4.6 (n=5,427), and [≥]4.7 (n=3,043).\n\nResultsOf 11,000 participants, 346 had a {Delta}eGFR/year of [≥]3. As compared with the participants with albumin levels of [≥]4.7 g/dL, the risk of decline in kidney function was higher not only in those with albumin levels of [≤]4.3 g/dL (adjusted OR = 2,29, 95% CI: 1.65-3.18) but also in 4.4-4.6 g/dL (adjusted OR = 1.60, 95% CI: 1.20-2.14).\n\nConclusionDecreased albumin level is an independent risk factor for rapid decline in kidney function even within the normal range.

epidemiology↗