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Transplanted Hepatocytes Function in Older Animals But Do Not Proliferate as Much as in Younger Ones
Gastroenterology and Hepatology News continued
ical consequences of this single nucleotide polymorphism (SNP). The group found that the SNP reduces expression of a nearby gene, SMAD7, a negative regulator of transforming growth factor (TGF)- signaling. If cellular levels of SMAD7 are reduced, critical signaling events could be set into motion, leading to carcinogenesis. Disruption of SMAD7 expression
has previously been implicated in progression of colorectal cancer. The authors conclude that, when viewed within the context of previous findings, their observation supports a direct role for SMAD7 in cancer progression, and very likely represents the causal basis for colorectal cancer risk associated with this chromosomal region. “We propose that
the novel SNP we have identified is the functional change leading to CRC predisposition through differential SMAD7 expression and, hence, aberrant TGF- signaling,” they state. See “The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression,” Genome Research, advanced online edition, April 24, 2009.
Transplanted Hepatocytes Function in Older Animals But Do Not Proliferate as Much as in Younger Ones epatocyte transplantation has been successful in a number of animal models, raising hopes that their use could overcome the shortage of donor livers and surgical issues, but the procedure has not been as successful in patients. Scientists at the Martin Luther University Hale-Wittenberg, Germany, may have determined why. Although donor age is not a factor, it seems that recipient age may make the difference. The German study found that older rats had a repopulation rate of only 2%, 10 times less than that observed in younger ones. Furthermore, the transplanted cells worked equally well in the old and young animals, as measured by glycogen storage, but the younger ani-
mals had significantly higher levels of insulin-like growth factor (IGF)-1 needed for proliferation. The new study is the first to offer a possible mechanism for the failure of transplanted hepatocytes to proliferate in many human patients, and the first to suggest a way to compensate for the problem, said Dr Peggy Stock, a postdoctoral fellow in the laboratory of Dr Bruno Christ. She reported the study April 19 at Experimental Biology 2009 in New Orleans. The presentation was part of the scientific program of the American Society for Investigative Pathology. The researchers isolated hepatocytes from both 4-week-old rats and animals ⬎35 weeks old. These healthy liver cells were then implanted into the livers of young animals (10 weeks, the equivalent of young adulthood) and “senescent” rats (⬎35 weeks). After 6 weeks, the
amount of hepatocyte proliferation was determined by an assay of CD26 enzyme activity. The recipient animals were CD26 knockouts, giving the researchers a way to determine which and how many hepatocytes were part of the recipient liver and which had the CD26 gene product, indicating they originated from the transplant. Repopulation of hepatocytes was 20% in young rats, whether the cells came from a young or old donor. In older rats, by contrast, repopulation was only 2%. All the transplanted and proliferated cells were functional, whether they were transplanted into old or young rats and whether they came from old or young rats. However, IGF-1 was significantly higher in the juvenile rats. The next step, say the researchers, is to inject IGF-1 in old rats and see if this pretreatment increases the proliferation levels of hepatocyte cells.
Jeremy Robin Jass, GI Pathologist eremy Robin Jass, Professor of Gastrointestinal Pathology at St. Mark’s Hospital and Imperial College in London, UK, died on November 30, 2008. The author of ⬎300 original papers and many books, Jass was equally highly esteemed as a research pathologist, clinician, and diagnostician. He challenged the belief
that metaplastic polyps, now widely known as hyperplastic polyps, were benign. See “The relation between metaplastic polyp and carcinoma of the colorectum” (Lancet 1983;321: 28 –30). Born May 13, 1951, Jass attended University College in London, and Westminster Medical School, also in London, UK, where he held early po-
sitions in pathology, acquiring his MD in 1983 and DSc in 1996. From 1996 to 1992, he served as Professor of Anatomical Pathology and Professor of Pathology at the University of Queensland in Brisbane, Australia, and was Professor and Department Head of Pathology at the University of Auckland School of Medicine in New Zealand. In 2002, he became
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ical consequences of this single nucleotide polymorphism (SNP). The group found that the SNP reduces expression of a nearby gene, SMAD7, a negative regulator of transforming growth factor (TGF)- signaling. If cellular levels of SMAD7 are reduced, critical signaling events could be set into motion, leading to carcinogenesis. Disruption of SMAD7 expression
has previously been implicated in progression of colorectal cancer. The authors conclude that, when viewed within the context of previous findings, their observation supports a direct role for SMAD7 in cancer progression, and very likely represents the causal basis for colorectal cancer risk associated with this chromosomal region. “We propose that
the novel SNP we have identified is the functional change leading to CRC predisposition through differential SMAD7 expression and, hence, aberrant TGF- signaling,” they state. See “The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression,” Genome Research, advanced online edition, April 24, 2009.
Transplanted Hepatocytes Function in Older Animals But Do Not Proliferate as Much as in Younger Ones epatocyte transplantation has been successful in a number of animal models, raising hopes that their use could overcome the shortage of donor livers and surgical issues, but the procedure has not been as successful in patients. Scientists at the Martin Luther University Hale-Wittenberg, Germany, may have determined why. Although donor age is not a factor, it seems that recipient age may make the difference. The German study found that older rats had a repopulation rate of only 2%, 10 times less than that observed in younger ones. Furthermore, the transplanted cells worked equally well in the old and young animals, as measured by glycogen storage, but the younger ani-
mals had significantly higher levels of insulin-like growth factor (IGF)-1 needed for proliferation. The new study is the first to offer a possible mechanism for the failure of transplanted hepatocytes to proliferate in many human patients, and the first to suggest a way to compensate for the problem, said Dr Peggy Stock, a postdoctoral fellow in the laboratory of Dr Bruno Christ. She reported the study April 19 at Experimental Biology 2009 in New Orleans. The presentation was part of the scientific program of the American Society for Investigative Pathology. The researchers isolated hepatocytes from both 4-week-old rats and animals ⬎35 weeks old. These healthy liver cells were then implanted into the livers of young animals (10 weeks, the equivalent of young adulthood) and “senescent” rats (⬎35 weeks). After 6 weeks, the
amount of hepatocyte proliferation was determined by an assay of CD26 enzyme activity. The recipient animals were CD26 knockouts, giving the researchers a way to determine which and how many hepatocytes were part of the recipient liver and which had the CD26 gene product, indicating they originated from the transplant. Repopulation of hepatocytes was 20% in young rats, whether the cells came from a young or old donor. In older rats, by contrast, repopulation was only 2%. All the transplanted and proliferated cells were functional, whether they were transplanted into old or young rats and whether they came from old or young rats. However, IGF-1 was significantly higher in the juvenile rats. The next step, say the researchers, is to inject IGF-1 in old rats and see if this pretreatment increases the proliferation levels of hepatocyte cells.
Jeremy Robin Jass, GI Pathologist eremy Robin Jass, Professor of Gastrointestinal Pathology at St. Mark’s Hospital and Imperial College in London, UK, died on November 30, 2008. The author of ⬎300 original papers and many books, Jass was equally highly esteemed as a research pathologist, clinician, and diagnostician. He challenged the belief
that metaplastic polyps, now widely known as hyperplastic polyps, were benign. See “The relation between metaplastic polyp and carcinoma of the colorectum” (Lancet 1983;321: 28 –30). Born May 13, 1951, Jass attended University College in London, and Westminster Medical School, also in London, UK, where he held early po-
sitions in pathology, acquiring his MD in 1983 and DSc in 1996. From 1996 to 1992, he served as Professor of Anatomical Pathology and Professor of Pathology at the University of Queensland in Brisbane, Australia, and was Professor and Department Head of Pathology at the University of Auckland School of Medicine in New Zealand. In 2002, he became
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