Donor-derived hepatocytes in human hematopoietic cell transplant recipients: evidence of fusion.
Reconstitution of hepatocytes by hematopoietic stem cells-a phenomenon which occurs in rodents under highly selective conditions-results from infrequent fusion between incoming myelomonocytes and host hepatocytes, with subsequent proliferation. Human hematopoietic stem cell transplant recipients hav...
| Publicado en: | Virchows Archiv: European Journal of Pathology Vol. 474; no. 3; pp. 365 - 375 |
|---|---|
| Autores principales: | , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Mar2019
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=135149187&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 135149187 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09456317 O1Z jtl: Virchows Archiv: European Journal of Pathology issn: 09456317 maglogo: N pubinfo: dt: Mar2019 vid: 474 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 135149187 135149187 NLM30539318 10.1007/s00428-018-2497-8 NLM30539318 135149187 ppf: 365 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Donor-derived hepatocytes in human hematopoietic cell transplant recipients: evidence of fusion. aug: au: Myerson, David Parkin, Rachael K. affil: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, 98109, Seattle, WA, USA sug: subj: Epithelial Cells Physiology Hematopoietic Stem Cell Transplantation Mortality Hematopoietic Stem Cell Transplantation Adverse Effects Chromosomes Cell Differentiation Genes In Situ Hybridization Methods Microscopy Methods Genetic Markers Cells Proteins Analysis Phenotype Treatment Outcomes Genotype Female Middle Age Male Cell Physiology Epithelial Cells Immunology Autopsy Adult Immunohistochemistry Methods Middle Aged: 45-64 years Adult: 19-44 years Female Male ab: Reconstitution of hepatocytes by hematopoietic stem cells-a phenomenon which occurs in rodents under highly selective conditions-results from infrequent fusion between incoming myelomonocytes and host hepatocytes, with subsequent proliferation. Human hematopoietic stem cell transplant recipients have been little studied, with some support for transdifferentiation (direct differentiation). We studied routinely obtained autopsy liver tissue of four female hematopoietic cell transplant recipients with male donors, using a highly specific conjoint immunohistochemistry in situ hybridization light microscopic technique. Hepatocyte nuclei were identified by cytokeratin (Cam5.2) staining and evaluated for X and Y chromosome content. Over 1.6 million hepatocytes were assessed for rare instances of donor origin, revealing a Y chromosome in 67. Mixed tetraploids (XXXY) and their nuclear truncation products (XXY, XY, Y) were directly demonstrated, with no detection of the male tetraploids (XXYY) that may result from transdifferentiation with subsequent tetraploidization, nor their unique truncation products (XYY, YY), implicating fusion as the mechanism. To determine whether it is the sole mechanism, we modeled the chromosome distribution based on the same probability of detection of each X chromosome, deriving parameters of sensitivity and female tetraploidy by best fit. We then hypothesized that the distribution of Y chromosome-containing cells could be predicted by a similar model. After modification to account for "clumpy" Y chromosomes, the observed results were in accord with the predicted results (p = 0.6). These results suggest that all the Y-containing cells, including apparent XY cells, derive from mixed tetraploids, consistent with fusion as the sole mechanism. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|