Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-3-27
pubmed:abstractText
Given the limits of allogenic organ transplantation, an ultimate therapeutic solution is to establish a self-organ from autologous stem cells and transplant them as syngrafts back into donor patients. It was reported previously that human mesenchymal stem cells (hMSC) that are cultivated in growing rodent embryos can differentiate within a spatially and temporally appropriate developmental milieu, facilitating the first step of nephrogenesis. As another step toward clinical application, the system was modified for progression to complete functional organogenesis. Rat embryos (E11.5) were isolated from uteri, and bone marrow-derived hMSC, which were transfected adenovirally with glial cell line-derived neurotrophic factor and retrovirally with LacZ, were implanted into the nephrogenic site. Forty-eight hours later, ureteric buds were elongated and initial branching was completed. The metanephroi were dissected out, developed further using in vitro organ culture for 24 h, transplanted into the omentum of a uninephrectomized rat, and grown for 2 wk. They enlarged and exhibited normal kidney structure and ultrastructure. hMSC-derived LacZ-positive cells were identified throughout the regenerated kidney and were morphologically identical to resident renal cells. Transplantation of developing metanephroi into the LacZ transgenic rat revealed that neo-kidney vasculature originated from the host circulation. Finally, fluid was collected from expanded ureters, and urea nitrogen and creatinine were measured. Levels were much higher in these fluids compared with transplanted rat sera (840.3 +/- 184.6 versus 30.4 +/- 10.8 and 10.1 +/- 3.1 versus 0.3 +/- 0.2 mg, respectively), suggesting that the neo-kidney may produce urine. Taken together, these findings suggest that hMSC can differentiate into a mature renal structure with the potential to replace lost kidney function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1026-34
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16524947-Animals, pubmed-meshheading:16524947-Animals, Genetically Modified, pubmed-meshheading:16524947-Base Sequence, pubmed-meshheading:16524947-DNA Primers, pubmed-meshheading:16524947-Female, pubmed-meshheading:16524947-Humans, pubmed-meshheading:16524947-Kidney, pubmed-meshheading:16524947-Lac Operon, pubmed-meshheading:16524947-Mesenchymal Stem Cell Transplantation, pubmed-meshheading:16524947-Mesenchymal Stem Cells, pubmed-meshheading:16524947-Neovascularization, Physiologic, pubmed-meshheading:16524947-Organ Culture Techniques, pubmed-meshheading:16524947-Polymerase Chain Reaction, pubmed-meshheading:16524947-Pregnancy, pubmed-meshheading:16524947-Rats, pubmed-meshheading:16524947-Rats, Inbred Lew, pubmed-meshheading:16524947-Rats, Sprague-Dawley, pubmed-meshheading:16524947-Regeneration, pubmed-meshheading:16524947-Transplantation, Autologous, pubmed-meshheading:16524947-Transplantation, Heterologous
pubmed:year
2006
pubmed:articleTitle
Xenobiotic kidney organogenesis from human mesenchymal stem cells using a growing rodent embryo.
pubmed:affiliation
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, Japan 105-8461. tyokoo@jikei.ac.jp
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't