Intramuscular transplantation of engineered hepatic tissue constructs corrects acute and chronic liver failure in mice

Navarro-Alvarez, Nalú; Soto-Gutiérrez, Alejandro; Chen, Yong; Caballero-Corbalan, José; Hassan, Wael; Kobayashi, Satoru; Kondo, Yoshitaka; Iwamuro, Masaya; Yamamoto, Kazuhide; Kondo, Eisaku; Tanaka, Noriaki; Fox, Ira J.; Kobayashi, Naoya

doi:10.1016/j.jhep.2009.11.019

Cited by 37 publications

(39 citation statements)

References 35 publications

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“…Following 5 additional days, all mice were euthanized for analysis, and LNs and native kidneys collected. (B): Dot plot comparing the number of BrdU label-retaining cells in control (mice 1-4) versus remnant kidneys after nephrectomy (mice [5][6][7][8]. The number of BrdU + cells was estimated using at least six different randomly selected microscopic fields.…”

Section: Nephrectomy Accelerates Kidney Organogenesismentioning

confidence: 99%

“…Ectopic organogenesis can be an alternative approach to provide compensatory function for the damaged organ [2,3]. Unfortunately, although several extravascular and a few immunoprivileged sites have been considered as potential ectopic transplantation sites for organs like pancreas [4] and liver [5], ectopic sites for kidney reconstruction have not yet been fully examined.…”

Section: Introductionmentioning

confidence: 99%

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The Lymph Node as a New Site for Kidney Organogenesis

Francipane

Lagasse

2015

Stem Cells Translational Medicine

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The shortage of organs for kidney transplantation has created the need to develop new strategies to restore renal structure and function. Given our recent finding that the lymph node (LN) can serve as an in vivo factory to generate or sustain complex structures like liver, pancreas, and thymus, we investigated whether it could also support kidney organogenesis from mouse renal embryonic tissue (metanephroi). Here we provide the first evidence that metanephroi acquired a mature phenotype upon injection into LN, and host cells likely contributed to this process. Urine-like fluid-containing cysts were observed in several grafts 12 weeks post-transplantation, indicating metanephroi transplants' ability to excrete products filtered from the blood. Importantly, the kidney graft adapted to a loss of host renal mass, speeding its development. Thus, the LN might provide a unique tool for studying the mechanisms of renal maturation, cell proliferation, and fluid secretion during cyst development. Moreover, we provide evidence that inside the LN, short-term cultured embryonic kidney cells stimulated with the Wnt agonist R-Spondin 2 gave rise to a monomorphic neuron-like cell population expressing the neuronal 200-kDa neurofilament heavy marker. This finding indicates that the LN might be used to validate the differentiation potential of candidate stem cells in regenerative nephrology. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:295-307

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Section: Nephrectomy Accelerates Kidney Organogenesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Lymph Node as a New Site for Kidney Organogenesis

Francipane

Lagasse

2015

Stem Cells Translational Medicine

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“…Although nonparenchymal cells represent only a small fraction of the total liver mass (6.5%), they are an essential component with functions that benefit and enhance overall hepatocyte metabolism, thus possibly favoring their survival which in regard to cell therapy could represent reduced hepatocyte amounts needed to achieve a therapeutic effect. 82,83 In the case of cholangiocytes, a conceivable advantage is the complementing of bile canaliculi with concomitant elimination of hepatocyte end products of metabolism. 84 The extent to which cholangiocyte transplant has been explored is short, reflecting the broader focus on hepatocytes.…”

Section: Modeling Of Cholangiocyte Diseasementioning

confidence: 99%

Current strategies to generate mature human induced pluripotent stem cells derived cholangiocytes and future applications

et al. 2017

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ABSTRACT. Stem cell research has significantly evolved over the last few years, allowing the differentiation of pluripotent cells into almost any kind of lineage possible. Studies that focus on the liver have considerably taken a leap into this novel technology, and hepatocyte-like cells are being generated that are close to resembling actual hepatocytes both genotypically and phenotypically. The potential of this extends from disease models to bioengineering, and even also innovative therapies for end-stage liver disease. Nonetheless, too few attention has been given to the non-parenchymal cells which are also fundamental for normal liver function. This includes cholangiocytes, the cells of the biliary epithelium, without whose role in bile modification and metabolism would impair hepatocyte survival. Such can be observed in diseases that target them, so called cholangiopathies, for which there is much yet to study so as to improve therapeutical options. Protocols that describe the induction of human induced pluripotent stem cells into cholangiocytes are scarce, although progress is being achieved in this area as well. In order to give the current view on this emerging research field, and in hopes to motivate further advances, we present here a review on the known differentiation strategies with sight into future applications.

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“…The nasoanal lengths were measured before their sacrifice. Lee index was calculated by the following equation 12,17 Lee index ¼ 1000…”

mentioning

confidence: 99%

Alteration of FXR phosphorylation and sumoylation in liver in the development of adult catch-up growth

Zhou

Zheng

et al. 2016

Exp Biol Med (Maywood)

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Catch-up growth in adult, is increasingly recognized as an important causative factor for the extremely prevalent insulin resistance-related diseases especially in developing countries/territories. We aimed to investigate the alteration of bile acids level, phosphorylation and sumoylation of its interacting protein, bile acid receptor/farnesoid X receptor and their downstream signaling pathway, as well as insulin sensitivity and lipid profile in catch-up growth in adult rats. Male Sprague-Dawley rats were randomly allocated into four groups for two sampling points: caloric restriction group, catch-up growth in adult refed with normal chow and their normal chow controls for four or eight weeks (N4, N8 individually).We found that total serum bile acids and farnesoid X receptor phosphorylation increased without significant changes in farnesoid X receptor sumoylation and its downstream small heterodimer partner expression at the end of caloric restriction stage, while the visceral fat decreased and insulin resistance never occurred in these animals; After refeeding, total serum bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as Cyp7a1, SREBP-1c mRNA levels were higher with significant decrease in small heterodimer partner expression, which is associated fat accumulation, and drastic insulin resistance in whole body and skeletal muscle. Our findings demonstrated that the fat accumulation and insulin resistance are associated with increases of bile acids, alteration of farnesoid X receptor phosphorylation, and sumoylation and its downstream signaling pathway. These changes of bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as their downstream signaling might be of importance in the etiology of fat accumulation and insulin resistance in catch-up growth in adult.

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Intramuscular transplantation of engineered hepatic tissue constructs corrects acute and chronic liver failure in mice

Cited by 37 publications

References 35 publications

The Lymph Node as a New Site for Kidney Organogenesis

The Lymph Node as a New Site for Kidney Organogenesis

Current strategies to generate mature human induced pluripotent stem cells derived cholangiocytes and future applications

Alteration of FXR phosphorylation and sumoylation in liver in the development of adult catch-up growth

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