Adult Human Blood Leukocytes as a Source of Tissue-Committed Progenitors for Cellular Therapy of Cardiovascular Disease.
Bibliographic record
Abstract
Abstract Significant progress has been made in recent years in developing therapeutic strategies for the treatment of a variety of cardiovascular disorders, mainly using bone marrow-derived progenitor cells. We hypothesized that blood leukocytes can also serve as a source for a wide range of clinical protocols. We report here the generation in vitro of both angiogenic cell precursors (ACP) and cardiomyocyte (CMC) progenitors from a newly discovered blood-derived multipotent cell population, termed synergetic cell population (SCP), and their function in vitro and in vivo. Progenitor cells were purified from healthy donor blood samples using density-based gradients. SCP-derived ACPs grown in the presence of autologous serum and VEGF exhibited an elongated, spindle-shaped morphology and expressed the stem cell markers CD34 (an average of 23.1% of cells), CD133 (10.2%), and CD117 (10.8%), and the endothelial markers KDR (8.9%), Tie-2 (24.8%), CD144 (41.2%), and CD31 (83.1%). Up to 30% of the cells exhibited Dil-Ac-LDL uptake, typical of endothelial cells. In vitro, ACPs showed organization into capillary tube structures when plated on extracellular matrix gels. An average of 50x106 ACPs were generated from 450 ml blood. CMC progenitors, which resulted from culturing SCP cells in medium containing autologous serum and bFGF followed by activation in a medium containing 5-azacytidine, appeared elongated with dark cytoplasm and expressed the cardiomyocyte markers desmin and troponin (on 19.7% and 52.3% of cells, respectively). The therapeutic potential of blood derived ACPs is currently being evaluated in patients with severe angina pectoris. Seventeen patients on maximal drug therapy have so far been prospectively enrolled, based upon identifying ischemic but viable myocardium in distribution of the coronary arteries that were totally occluded. ACPs (25x106, SE=4.9) were injected via a catheter into the coronary artery. Preliminary results demonstrate safety and improved clinical symptoms at 3 months vs. baseline. Mean Canadian Cardiovascular Scale for angina severity decreased from 1.8±0.8 to 1.06±0.3 (P=0.062) and exercise capacity measured by metabolic equivalents increased from 6.3±2.3 to 7.4 ±2.8 (P= 0.0083). One patient died two weeks after the treatment due to acute myocardial infarction. However, coronary angiography demonstrated acute occlusion of an artery not treated with cells. These results suggest the treatment is safe with preliminary short term beneficial effect. Continued follow-up is currently being conducted to determine the long-term effects of this therapy in a larger number of patients. In order to examine the functional mechanisms underlying the therapeutic effects of ACPs and CMC progenitors, an in-vivo experiment is also being carried out in a nude rat acute myocardial infarction model. We demonstrate here that a newly-discovered multipotent cell population which we term SCP can be isolated from peripheral blood and differentiated into therapeutically effective tissue-committed progenitor cells. The SCP contains hematopoietic stem cells and supportive cells enabling differentiation into various lineages, such as ACPs, cardiomyocyte and neural progenitors (the latter reported in a separate abstract by our group) which have thus been generated.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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) | 0.001 | 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".