Liver Engraftment by Transplanted Human Progenitor Cells with High Aldehyde Dehydrogenase Activity in a Novel Model, NOD/SCID/MPSVII Mice.
Bibliographic record
Abstract
Abstract Hematopoietic stem cells (HSC) have been reported to generate cells other than the blood lineage and thus hold enormous promise for repairing damaged tissues. Evidence from our lab and others suggests that hepatocytes can be derived from HSC. However, the frequency of HSC-derived hepatocytes varies tremendously among various studies which use different stem cell subsets and different mouse models. Therefore, the significance of hematopoietic stem cell contribution to the repair of liver damage is still controversial. To further explore this potential, we used the beta-glucuronidase (GUSB)-deficient NOD/SCID/MPSVII mouse model for better identification of engrafted human cells. We and others have previously shown that lineage depleted (lin−) human umbilical cord blood-derived cells with high aldehyde dehydrogenase activity (ALDHhi) are enriched for primitive HSC. In the current studies, ALDHhi lin− cells were transplanted into irradiated NOD/SCID/MPSVII mice. One month after transplantation, carbon tetrachloride (CCl4) was administrated into the mice twice a week for 4 weeks to induced liver damage. In this model, ALDHhi lin− cells gave rise to robust hematopoietic reconstitution (71%±13.1 in bone marrow, 12.8%±4% in peripheral blood and 10.7%±8.8% in spleen) while ALDHlolin− cells failed to engraft. In the liver, engraftment of human cells in mice tansplanted with ALDHhi lin− cells was demonstrated by the presence of human Alu DNA using PCR. CD45+ cells were detected by both FACS (2.11%±1.1) and by immunohistological staining in the liver sections. GUSB expression was frequently evident in kuffer cells adjacent to blood vessels and to a lesser extent in the liver parenchyma. GUSB+ cells were more abundant than CD45+ cells. Most interestingly, human liver-specific a-1-antitrypsin mRNA was detected in the recipient murine livers by RT-PCR analysis. Human albumin- expressing cells were also found in these livers, although such cells were rare as compared to human CD45+ or GUSB+ cells. In contrast, human cells were not detected in the livers of mice tansplanted with ALDHlolin− cells in any of our assays. Thus, ALDH-expressing progenitor cells demonstrated potent engraftment of variable cellular phenotypes, suggesting that these adult progenitor cells should be further explored in transplantation models of tissue damage. Our data also support the idea that hematopoietic stem cells may home to the injured liver and release trophic factors that hasten tissue repair, while direct differentiation of these stem cells to hepatocytes or fusion of these cells with hepatocytes is rare and contributes to a lesser extent to liver repair.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".