Effects of Irradiation on the Functional Characteristics of Human Bone Marrow Mesenchymal Stromal/Stem Cells
Notice bibliographique
Résumé
Abstract Total-body irradiation is frequently used as a conditioning treatment for hematopoietic stem cell transplantation. Although previous studies have demonstrated that irradiation induces apoptosis and senescence in hematopoietic stem/progenitor cells (HSPCs), its effect on the functional characteristics of human bone marrow mesenchymal stromal/stem cells (BM-MSCs) is largely unknown. Human BM-MSCs were isolated from BM samples according to our previously published method (Stem Cells 32:2245, 2014). BM samples were purchased from AllCells (Emeryville, CA). For the irradiation experiments, BM-MSCs were g-irradiated (Cesium-137) with various doses ranged from 2 to 12 Gy by a Gammmacell Irradiator (Best Theratronics Ltd, Ontario, Canada). We first examined the expansion of g-irradiated human BM-MSCs. When BM-MSCs (0.5 x 105) were cultured on a 10-cm culture dish in advanced-minimal essential medium (Invitrogen, Carlsbad, CA) supplemented with 5% fetal bovine serum (FBS, Invitrogen), the cells expanded rapidly, reached near confluence within 2 weeks, and the average number of cells on day 7 was 6.4 x 105. On the other hand, the number of BM-MSCs that were g-irradiated at 2 Gy, 4 Gy and 12 Gy on day 7 was low at 0.8 x 105, 0.3 x 105, and 0.2 x 105, respectively. The recovery of cell expansion was irradiation dose-dependent; the average number of cells on day 28 was 8.6 x 105 (2 Gy), 3.7 x 105 (4 Gy) and 0.3 x 105 (12 Gy). Next, hematopoiesis-supportive capabilities of g-irradiated human BM-MSCs were examined. Human CD34 positive HSPCs were co-cultured with g-irradiated BM-MSCs in StemSpan Serum-Free Expansion Medium (STEMCELL Technologies, Vancouver, Canada) supplemented with stem cell factor (SCF), Flt3-ligand (Flt3-L), thrombopoietin (TPO), and interleukin (IL)-3. After 10-day co-culture, the expansion of HSPCs was comparable among BM-MSCs with or without g-irradiation. The number of CD33 positive myeloid progenitor cells in the expanded cells was also comparable among BM-MSCs with or without g-irradiation. However, when human CD34 positive HSPCs were co-cultured with g-irradiated BM-MSCs in the complete medium supplemented with 10 ng/mL SCF and 5 ng/mL FLt3-L for 4 weeks, the generation of CD19 positive cells was impaired. The number of CD19 positive cells, which were generated in co-cultures of CD34 positive HSPCs (0.2 x 104) with BM-MSCs that were not g-irradiated, was 1.4 x 104, whereas those in co-cultures with BM-MSCs that were g-irradiated at 2 Gy, 4 Gy and 12 Gy were 0.09 x 104, 0.04 x 104, 0.05 x 104, respectively. With respect to the expression of B-cell lymphopoiesis-associated humoral factors in BM-MSCs, mRNA expression levels of CXCL12/SDF-1, Flt3-L, SCF and IL-7 were decreased in g-irradiated BM-MSCs. Especially, the expression of Flt3-L in BM-MSCs was reduced soon after irradiation exposure. Finally, we found that the osteogenic, adipogenic and chondrogenic differentiation capability of the g-irradiated BM-MSCs were dysregulated, as assessed by both the expression of lineage-specific molecular markers. In conclusion, g-irradiation compromised expansion, differentiation and B-cell lymphopoiesis-supportive capabilities of human BM-MSCs in a dose-dependent manner. This study could provide new insights into the role of BM-MSCs in the pathogenesis of immunologic and non-immunologic complications after hematopoietic stem cell transplantation. 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
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 ».