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        Improvement of Kidney Failure With Fetal Kidney Precursor Cell Transplantation

        Kim, Sang-Soo,Park, Heung Jae,Han, Joungho,Gwak, So-Jung,Park, Moon Hyang,Song, Kang Won,Rhee, Yun Hee,Min Chung, Hyung,Kim, Byung-Soo Lippincott Williams Wilkins, Inc. 2007 Transplantation Vol.83 No.9

        BACKGROUND.: Current therapies for end-stage renal disease have severe limitations. Dialysis is only a temporary treatment and does not restore kidney function. Transplantation is limited by donor organ shortage and immune-related problems. Here, we show that the transplantation of fetal kidney precursor cells reconstitutes kidney tissues, reduces uremic symptoms, and provides life-saving metabolic support in kidney failure animal models. METHODS.: Kidney failure was surgically induced by resecting kidneys, leaving approximately 1/6 of the total kidney mass (5/6 nephrectomy). Fetal kidney precursor cells were isolated from metanephroi of E17.5 rat fetuses using collagenase/dispase digestion. Five weeks after the nephrectomy procedure, isolated fetal kidney precursor cells were transplanted under the kidney capsule of rats using fibrin gel matrix. Six and ten weeks after transplantation, animals were analyzed biochemically and the grafts were retrieved for histological analyses. RESULTS.: Five weeks after the nephrectomy, glomerular hypertrophy, and increased blood urea nitrogen and serum creatinine levels were observed. The cell transplantation into the kidneys of kidney failure-induced rats resulted in kidney tissue reconstitution and the transplanted cells were observed in the reconstitution region of the kidneys as evidenced by the presence of fluorescently labeled cells. In addition, biochemical parameters from serum and urine samples showed improved kidney functions compared with non-treated group without severe immune response after ten weeks. CONCLUSION.: Transplanting fetal kidney precursor cells showed the potential for the partial augmentation of kidney structure and function in the treatment of kidney failure.

      • Kidney Tissue Reconstruction by Fetal Kidney Cell Transplantation: Effect of Gestation Stage of Fetal Kidney Cells

        Kim, Sang-Soo,Gwak, So-Jung,Han, Joungho,Jae Park, Heung,Hyang Park, Moon,Won Song, Kang,Woo Cho, Seung,Rhee, Yun Hee,Chung, Hyung Min,Kim, Byung-Soo Wiley (John WileySons) 2007 Stem cells Vol.25 No.6

        <P>Dialysis and kidney transplantation, current therapies for kidney failure, have limitations such as severe complications, donor shortage, and immune-related problems. The development of an alternative treatment for kidney failure is demanded. The present study shows that the transplantation of fetal kidney cells reconstitutes functional kidney tissue, and that the gestation stage of kidney cells influences the kidney reconstitution. Fetal kidney cells were isolated from metanephroi of rat fetuses at various gestation stages and transplanted into the omentum or kidney of immunodeficient mice. Immunophenotype analysis of fetal kidney cells showed apparent expression of stem cell markers. Three weeks after transplantation, histological analyses of retrieved grafts revealed the formation of kidney structures, including fluorescently labeled transplanted cells, suggesting the potential of fetal kidney cells to reconstitute kidney tissues. The grafts retrieved from omentum contained cystic fluids with concentrated solutes. However, transplanted early fetal kidney cells had also differentiated into nonrenal tissues such as bone and cartilage. In addition, transplantation of fetal kidney cells from a later gestation stage resulted in poor kidney structure formation. Kidney-specific genes were strongly expressed in the earlier cell transplants. The cells at an earlier gestation stage had higher colony forming ability than the cells at a later stage. This study demonstrates the reconstitution of kidney tissue by transplanting fetal kidney cells and the presence of an optimal time window in which fetal kidney cells regenerate kidney tissues. Disclosure of potential conflicts of interest is found at the end of this article.</P>

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        A Genome-Wide Association Study Identifies UTRN Gene Polymorphism for Restless Legs Syndrome in a Korean Population

        ChulHyun Cho,JiHye Choi,SeungGul Kang,HoKyoung Yoon,YoungMin Park,JoungHo Moon,KiYoung Jung,JinKyu Han,HongBum Shin,HyunJi Noh,YongSeo Koo,Leen Kim,HyunGoo Woo,HeonJeong Lee 대한신경정신의학회 2017 PSYCHIATRY INVESTIGATION Vol.14 No.6

        Objective-Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population. Methods-We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results. Results-In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10-6) in MPHOSPH6 on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10-6) and rs9390170 (OR=0.6778, p=7.67×10-6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170 in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10-18) in BTBD9 was associated with RLS. Conclusion-From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by UTRN, is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.

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