A Potential New Application of Mobilization/Leukapheresis for Enrichment of Peripheral Blood in Circulating Non-Hematopoietic CXCR4+CD45− Tissue-Committed Stem Cells (TCSC) for Organ/Tissue Regeneration.
Bibliographic record
Abstract
Abstract During mobilization hematopoietic stem cells (HSC) egress from the bone marrow (BM) into peripheral blood (PB) where they temporarily circulate and can be collected by leukapheresis. However, recently we demonstrated that BM, in addition to HSC, contains heterogeneous populations of CXCR4+ tissue-committed stem cells (TCSC) and we contend that the contribution of these cells to organ/tissue regeneration after transplantation of BM cells has been misinterpreted as evidence for “plasticity” or “trans-dedifferentiation” of HSC (Leukemia2004:18;29–40). To determine whether TCSC could also be mobilized into PB we i) evaluated the presence of these cells in the PB of G-CSF-mobilized patients (n=11), ii) attempted to increase mobilization of the TCSC in a murine model by combining G-CSF with T140 (a CXCR4 antagonist) or SB290157 (the C3a complement fragment receptor antagonist which we have found to desensitize the responsiveness of HSC to SDF-1), and iii) tested the hypothesis that TCSC could also be mobilized into PB during stress related to tissue/organ injury, e.g., heart infarct, stroke, partial body irradiation. The presence of mobilized/circulating TCSC in PB was evaluated by i) real-time RT-PCR, ii) immunohistochemical staining for TCSC markers and iii) demonstrating the potential of mobilized TCSC to grow neurospheres or to form myotubes in vitro. We present evidence for the first time that i) G-CSF efficiently enhances the release into PB not only of HSC but also of TCSC expressing markers for early skeletal muscle, myocardium, neural tissue, pancreas and liver, ii) a combination of G-CSF with T140 or SB290157 is 25–30 times more effective in selectively mobilizing TCSC compared to G-CSF alone, and iii) TCSC are also mobilized to PB during stress related to heart infarct, stroke or partial body irradiation. Furthermore, we observed that TCSC, like HSC, express CXCR4 and Sca-1 but do not radioprotect lethally irradiated mice and, unlike HSC, are CD45-negative. Based on these findings we postulate that mobilization/leukapheresis procedures may find a new application for obtaining TCSC for use in tissue/organ regeneration. We are currently testing this hypothesis in murine models.
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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) | 0.000 | 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 | 0.001 |
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".