Matrix metalloproteinase and tissue inhibitors of metalloproteinase secretion by haematopoietic and stromal precursors and their production in normal and leukaemic long‐term marrow cultures
Bibliographic record
Abstract
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate the turnover of the extracellular matrix and may modulate the biology of haematopoietic cells. We investigated whether MMPs and TIMPs are produced in long-term marrow cultures (LTMCs) established from normal donors and acute myelogenous leukaemia (AML) patients, and by fibroblast- (F), granulocyte macrophage- (GM) and megakaryocyte- (Meg) colony-forming unit (CFU) and erythroid burst-forming unit (BFU-E)-derived precursor cells. ProMMP-9 levels were highest (> 400 ng/ml) at week 1 of normal LTMC, whereas proMMP-2, TIMP-1, TIMP-2 and TIMP-3 levels peaked (up to 1000 ng/ml) after the establishment of the adherent layer. In LTMC from AML patients, these patterns of secretion were reversed. Moreover, we found that after a 24 h incubation in serum-free media, normal CFU-GM-, BFU-E- and CFU-Meg-derived cells secreted proMMP-9 and CFU-F-derived cells proMMP-2, in contrast to cells from LTMC adherent layer which secreted both active and latent forms of MMP-2 and MMP-9 under serum-free conditions. However, when these adherent cells were incubated in 12.5% fetal calf or horse serum or complete LTMC growth media, active forms of MMP-2 and MMP-9 were no longer detectable, and TIMP levels increased. Hence, we concluded that (i) MMPs/TIMPs are secreted by normal human bone marrow haematopoietic and stromal cells and may play an important role in intercellular cross-talk in haematopoiesis; and (ii) only latent forms of MMPs are present under LTMC conditions, indicating that the specific media used for weekly re-feeding of LTMC can block activation of MMP-2 and MMP-9, maintaining the integrity of the stromal layer and supporting haematopoiesis in vitro.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".