The efficacy and safety of bone marrow-derived cells extract in the management of Sjögren's-like disease in NOD mouse model
Notice bibliographique
Résumé
Sjögren’s syndrome (SS) is a common, chronic, and debilitating autoimmune diseases, affecting nearly 4 million North Americans. It affects females approximately 14 times higher than males, most of which are postmenopausal women. It is characterized by exocrine glands lymphocytic infiltration and glandular destruction. SS is a slowly progressing disease that starts decades before the patients experience any symptoms. Patients will experience dry eyes and mouth, and a wide range of extra-glandular manifestations, including fatigue, arthritis, arthralgia, pulmonary, neurological, cutaneous, and muscular manifestations, and lymphoma. The generalized manifestations lead to a significantly compromised quality of life. The pathogenesis is complex and still not fully understood due to the difficulty of studying the disease in humans and the ambiguity of its etiology. Unfortunately, no cure has been found yet. The current management is directed toward dryness symptoms palliation, prevention of further complications, and when serious systemic conditions emerge, immunosuppressive agents are indicated. The aim of this PhD thesis is to test a new treatment modality that combines the characteristics of cell and biologic therapies. The risks associated with both treatments complicate the clinical condition of significantly compromised patients. Therefore, we employed the success of BM-derived cells in managing SS in the form of a biologic therapy, by extracting their proteins and using it as a potential SS therapy. We tested the ability of bone marrow BM-derived cells extract in decreasing inflammation and promoting trophic changes in the glandular tissue in the NOD mouse model, when injected before SS immune dysregulation intensifies. First, we tested the effectiveness of BM-derived mesenchymal stromal cells extract (MSCsE) versus BM-derived mesenchymal stromal cells in preventing or alleviating the symptoms of SS. The treated groups (MSCs and MSCsE) showed comparable positive results regarding these treatments efficacy in preserving the salivary and lacrimal flow rates. This preservation was the outcome of maintained cell proliferation and specialized cell subpopulations and genes associated with regeneration. Additionally, SS immune dysregulation was, somewhat, managed via the elevation of IL-10 and suppression of B cells. Second, we assessed the effectiveness of BM cell extract (BMCE) in hindering SS immune dysregulation in NOD mice and we evaluated its systemic safety. The treated mice showed comparable results to those of MSCsE and MSCs; suggesting a common and/or possibly different, proteins composition in both therapies, that might have led to the recorded regenerative outcomes. Additionally, we tested the systemic safety of BMCE as an example of the cell extract concept. Surprisingly, the BMCE-treated NOD mice showed no difference in comparison to the control (saline-treated) NOD mice and the non-SS and non-treated control mouse model, ICRIn conclusion, BM-derived cells extract treatment has shown promising results in managing SS, and we may recommend the use of BMCE and MSCsE as potential treatment modality for patients. They exerted immune regulatory and trophic effects to injured exocrine tissues. Additionally, the various risks associated with biologic and cellular therapies are minimal when using the extract. Biologic therapies are associated with opportunistic infections due to a complete interference with cytokines or blocking B cells as strategies to manage SS; however, this does not apply to cell extracts. Additionally, cellular therapies require myeloablative conditioning and their use is complicated with Graft versus Host Disease (GvHD) and malignancy. However, using the cell extract did not lead to complications in our mice after a follow up period of 16 weeks and no prior preparative procedures were required. Yet, we may not exclude possible changes which might appear with longer in vivo follow up periods
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 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) | 0,000 | 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 tête enseignante, 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 ».