Human Cord Blood Cells with Rapid In Vivo Platelet Regenerating Activity in NOD/SCID-IL-2Rγc-/- Mice Show Variable Aldehyde Dehydrogenase Activity.
Notice bibliographique
Résumé
Abstract Abstract 2429 Poster Board II-406 Human cord blood (CB) has emerged as an attractive source of hematopoietic cells for patients lacking a suitable donor. However, marked delays in platelet and immune recovery pose significant challenges to the use of CB cells as transplants for either children or adult patients. These difficulties in the use of CB have been attributed to low absolute numbers of repopulating cells (RCs) in most CB units which is not readily overcome by simply combining multiple units. Xenotransplantation of human hematopoietic cells into highly immunodeficient sublethally irradiated NOD/SCID mice has proven to be a powerful approach to characterize different types of primitive human hematopoietic cells with repopulating potential. However, the residual NK activity intrinsic to NOD/SCID mice poses a significant barrier to the engraftment of intermediate types of repopulating human cells and also to the terminal stages of their differentiation, as shown by recent studies using more immunodeficient mice as hosts. Nevertheless, the cells responsible for early platelet recovery post-transplant and factors that regulate their activity remain largely unknown. To address this issue, we have developed a quantitative and sensitive assay for characterizing the phenotypes of human CB cells that regenerate mature platelets detectable in the blood of NOD/SCID-IL-2Rγc-/- mice 3-6 weeks post-transplant. Lineage marker-negative (Lin-) human CB cells were stained with Aldefluor and then those with low light side-scattering properties were further separated by FACS according to whether they displayed aldehyde dehydrogenase activity above (ALDH+) or below (ALDH-) that detected in the presence of an ALDH inhibitor. Assays of different pooled human CB preparations showed that the most primitive class of in vitro megakaryocyte (Mk) colony-forming cells and cells responsible for rapid human platelet production in NOD/SCID-IL-2Rγc-/- mice were variably and comparably distributed between the small ALDH+ and prevalent ALDH- fractions. From 3 experiments, the following values were obtained for the ALDH+ and ALDH- subsets, respectively; ALDH+ - mature CFU-Mk = 47.8±21.3% of the total Lin- fraction, intermediate CFU-Mk = 66.3±25.4%, primitive CFU-Mk = 75.5±14.0%, 3-week platelet-producing STRC = 63.8±12.3%, 6-week platelet-producing STRC = 81.5±5.8%; and ALDH- - mature CFU-Mk = 52.2±21.3% of the total Lin- fraction, intermediate CFU-Mk = 33.7±25.4%, primitive CFU-Mk = 24.5±14.0%, 3-week platelet-producing STRC = 36.2±12.3%, 6-week platelet-producing STRC = 18.5±5.8%. Limiting dilution assays revealed 1 in 830 Lin-ALDH+ CB cells to be a cell that can produce detectable platelets in vivo within 3 weeks (95% CI = 1 in 534 to 1 in 1290) but only 1 in 1996 (95% CI = 1 in 1226 to 1 in 3247) within 6 weeks. The present study demonstrates the feasibility of using NOD/SCID-IL-2Rγc-/- mice for the sensitive detection of human CB cells with in vivo platelet regenerating activity and suggests that these may be closely related to primitive cells with in vitro Mk clonogenic activity (>50 Mk per colony). Biologically important platelet progenitors may thus be heterogeneous with respect to ALDH+ activity. Disclosures: No relevant conflicts of interest to declare.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».