دورية أكاديمية
أعرض في EDS

Functionality of bone marrow mesenchymal stromal cells derived from head and neck cancer patients - A FDA-IND enabling study regarding MSC-based treatments for radiation-induced xerostomia.

التفاصيل البيبلوغرافية
العنوان: Functionality of bone marrow mesenchymal stromal cells derived from head and neck cancer patients - A FDA-IND enabling study regarding MSC-based treatments for radiation-induced xerostomia.
المؤلفون: Blitzer GC; Department of Human Oncology, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Paz C; Department of Human Oncology, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Glassey A; Department of Human Oncology, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Ganz OR; Department of Medicine, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Giri J; Department of Medicine, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Pennati A; Department of Medicine, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA; UW Carbone Cancer Center, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Meyers RO; Department of Human Oncology, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA; Department of Medicine, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Bates AM; Department of Human Oncology, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Nickel KP; Department of Human Oncology, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Weiss M; Department of Human Oncology, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Morris ZS; Department of Human Oncology, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Mattison RJ; Department of Medicine, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA; UW Carbone Cancer Center, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., McDowell KA; Department of Medicine, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Croxford E; Department of Biostatistics and Medical Informatics, 610 Walnut Street, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53726 USA., Chappell RJ; Department of Biostatistics and Medical Informatics, 610 Walnut Street, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53726 USA; UW Carbone Cancer Center, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Glazer TA; Department of Surgery, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Rogus-Pulia NM; Department of Medicine, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA; UW Carbone Cancer Center, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA; Geriatric Research Education and Clinical Center, 2500 Overlook Terrace, William S. Middleton Memorial Veterans Hospital, Madison, WI 53705 USA., Galipeau J; Department of Medicine, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA; UW Carbone Cancer Center, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA., Kimple RJ; Department of Human Oncology, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA; UW Carbone Cancer Center, 600 Highland Ave, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53705 USA. Electronic address: rkimple@humonc.wisc.edu.
المصدر: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology [Radiother Oncol] 2024 Mar; Vol. 192, pp. 110093. Date of Electronic Publication: 2024 Jan 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Scientific Publishers Country of Publication: Ireland NLM ID: 8407192 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0887 (Electronic) Linking ISSN: 01678140 NLM ISO Abbreviation: Radiother Oncol Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : Elsevier Scientific Publishers
Original Publication: Amsterdam : Elsevier Science Publishers, c1983-
مواضيع طبية MeSH: Xerostomia*/etiology , Xerostomia*/therapy , Head and Neck Neoplasms*/radiotherapy , Radiation Injuries*/etiology , Radiation Injuries*/therapy , Mesenchymal Stem Cells*, Humans ; Animals ; Mice ; Bone Marrow ; Salivary Glands ; Bone Marrow Cells
مستخلص: Purpose: Salivary dysfunction is a significant side effect of radiation therapy for head and neck cancer (HNC). Preliminary data suggests that mesenchymal stromal cells (MSCs) can improve salivary function. Whether MSCs from HNC patients who have completed chemoradiation are functionally similar to those from healthy patients is unknown. We performed a pilot clinical study to determine whether bone marrow-derived MSCs [MSC(M)] from HNC patients could be used for the treatment of RT-induced salivary dysfunction.
Methods: An IRB-approved pilot clinical study was undertaken on HNC patients with xerostomia who had completed treatment two or more years prior. Patients underwent iliac crest bone marrow aspirate and MSC(M) were isolated and cultured. Culture-expanded MSC(M) were stimulated with IFNγ and cryopreserved prior to reanimation and profiling for functional markers by flow cytometry and ELISA. MSC(M) were additionally injected into mice with radiation-induced xerostomia and the changes in salivary gland histology and salivary production were examined.
Results: A total of six subjects were enrolled. MSC(M) from all subjects were culture expanded to > 20 million cells in a median of 15.5 days (range 8-20 days). Flow cytometry confirmed that cultured cells from HNC patients were MSC(M). Functional flow cytometry demonstrated that these IFNγ-stimulated MSC(M) acquired an immunosuppressive phenotype. IFNγ-stimulated MSC(M) from HNC patients were found to express GDNF, WNT1, and R-spondin 1 as well as pro-angiogenesis and immunomodulatory cytokines. In mice, IFNγ-stimulated MSC(M) injection after radiation decreased the loss of acinar cells, decreased the formation of fibrosis, and increased salivary production.
Conclusions: MSC (M) from previously treated HNC patients can be expanded for auto-transplantation and are functionally active. Furthermore IFNγ-stimulated MSC(M) express proteins implicated in salivary gland regeneration. This study provides preliminary data supporting the feasibility of using autologous MSC(M) from HNC patients to treat RT-induced salivary dysfunction.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
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معلومات مُعتمدة: P50 DE026787 United States DE NIDCR NIH HHS; UG3 DE030431 United States DE NIDCR NIH HHS; UH3 DE030431 United States DE NIDCR NIH HHS; P30 CA014520 United States CA NCI NIH HHS; F31 DE031180 United States DE NIDCR NIH HHS; R01 DK109508 United States DK NIDDK NIH HHS; UL1 TR002373 United States TR NCATS NIH HHS; P50 CA278595 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Cell therapy; Head and neck cancer; Mesenchymal Stromal Cells; Radiation; Xerostomia
تواريخ الأحداث: Date Created: 20240115 Date Completed: 20240227 Latest Revision: 20240605
رمز التحديث: 20240605
مُعرف محوري في PubMed: PMC10922976
DOI: 10.1016/j.radonc.2024.110093
PMID: 38224919
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-0887
DOI:10.1016/j.radonc.2024.110093