Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background:

Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia.

Methods/design:

This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy.

Discussion:

This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia.

Trial registration:

This study was registered with the Japan Registry of Clinical Trials ( http://jrct.niph.go.jp) as jRCTb070190057.

Related collections

Most cited references 21

Record: found
Abstract: found
Article: not found

A structured review and theme analysis of papers published on 'quality of life' in head and neck cancer: 2000-2005.

Erin S Rogers, Debra Murphy, S. Ahad (2007)

Over the past 10 years, quality of life (QOL) has been increasingly recognised as an important outcome parameter in head and neck cancer. Validated questionnaires have emerged and there has been an increase in the number of papers published each year. The aim of this article is to review the literature over the past five years (2000-2005 inclusive), to identify papers reporting outcomes using patient self-competed questionnaires and group these into themes. The tabulated summary allows for the areas of health related quality of life research to be identified and to explore issues that are perhaps deficit in the literature. The three authors independently searched the literature published in the English language using the ISI search engine with cross-reference using Pub Med and Ovid. The search terms were; quality of life, questionnaire, and head and neck cancer. Studies were placed in to one of five themes. There were 165 studies identified. The numbers in each theme were predictors of QOL [Hassanein KA, Musgrove BT, Bradbury E. Functional status of patients with oral cancer and its relation to style of coping, social support and psychological status. Br J Oral Maxillofac Surg 2001;39:340-5.], functional outcome [Klug C, Neuburg J, Glaser C, Schwarz B, Kermer C, Millesi W. Quality of life 2-10 years after combined treatment for advanced oral and oropharyngeal cancer. Int J Oral Maxillofac Surg 2002;31:664-9.], questionnaire development [Hanna E, Sherman A, Cash D, Adams D, Vural E, Fan CY, et al. Quality of life for patients following total laryngectomy vs chemoradiation for laryngeal preservation. Arch Otolaryngol Head Neck Surg 2004;130:875-9.], randomised clinical trials [Kanatas AN, Rogers SN. A national survey of health-related quality of life questionnaires in head and neck oncology. Ann R Coll Surg Engl 2004;86:6-10.], and reviews [Kanatas AN, Rogers SN. A national survey of health-related quality of life questionnaires in head and neck oncology. Ann R Coll Surg Engl 2004;86:6-10.]. Although many facets of HRQOL following head and neck cancer have been explored over the last five years the paper identifies issues where research is still lacking.

0 comments Cited 54 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Concise Review: Salivary Gland Regeneration: Therapeutic Approaches from Stem Cells to Tissue Organoids

Isabelle M.A. Lombaert, Mohammad M Movahednia, Christabella Adine … (2016)

The human salivary gland (SG) has an elegant architecture of epithelial acini, connecting ductal branching structures, vascular and neuronal networks that together function to produce and secrete saliva. This review focuses on the translation of cell- and tissue-based research toward therapies for patients suffering from SG hypofunction and related dry mouth syndrome (xerostomia), as a consequence of radiation therapy or systemic disease. We will broadly review the recent literature and discuss the clinical prospects of stem/progenitor cell and tissue-based therapies for SG repair and/or regeneration. Thus far, several strategies have been proposed for the purpose of restoring SG function: (1) transplanting autologous SG-derived epithelial stem/progenitor cells; (2) exploiting nonepithelial cells and/or their bioactive lysates; and (3) tissue engineering approaches using 3D (three-dimensional) biomaterials loaded with SG cells and/or bioactive cues to mimic in vivo SGs. We predict that further scientific improvement in each of these areas will translate to effective therapies toward the repair of damaged glands and the development of miniature SG organoids for the fundamental restoration of saliva secretion.

0 comments Cited 51 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Bone marrow-derived cells rescue salivary gland function in mice with head and neck irradiation.

Younan Liu, Trong Tran, Eva Mezey … (2010)

Treatment for most patients with head and neck cancers includes ionizing radiation. A consequence of this treatment is irreversible damage to salivary glands (SGs), which is accompanied by a loss of fluid-secreting acinar-cells and a considerable decrease of saliva output. While there are currently no adequate conventional treatments for this condition, cell-based therapies are receiving increasing attention to regenerate SGs. In this study, we investigated whether bone marrow-derived cells (BMDCs) can differentiate into salivary epithelial cells and restore SG function in head and neck irradiated mice. BMDCs from male mice were transplanted into the tail-vein of 18Gy-irradiated female mice. Salivary output was increased in mice that received BMDCs transplantation at week 8 and 24 post-irradiation. At 24 weeks after irradiation (IR), harvested SGs (submandibular and parotid glands) of BMDC-treated mice had greater weights than those of non-treated mice. Histological analysis shows that SGs of treated mice demonstrated an increased level of tissue regenerative activity such as blood vessel formation and cell proliferation, while apoptotic activity was increased in non-transplanted mice. The expression of stem cell markers (Sca-1 or c-kit) was detected in BMDC-treated SGs. Finally, we detected an increased ratio of acinar-cell area and approximately 9% of Y-chromosome-positive (donor-derived) salivary epithelial cells in BMDC-treated mice. We propose here that cell therapy using BMDCs can rescue the functional damage of irradiated SGs by direct differentiation of donor BMDCs into salivary epithelial cells. Copyright © 2010 Elsevier Ltd. All rights reserved.

0 comments Cited 44 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Wolters Kluwer Health

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: 26 June 2020

Publication date (Electronic): 26 June 2020

Volume: 99

Issue: 26

Electronic Location Identifier: e20788

Affiliations

[a ]Basic and Translational Research Center for Hard Tissue Disease

[b ]Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki

[c ]CellAxia Inc., Tokyo

[d ]Department of Regenerative Oral Surgery, Unit of Translational Medicine

[e ]Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Sciences

[f ]Transfusion and Cell Therapy Unit, Nagasaki University

[g ]Department of Applied Prosthodontics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki

[h ]Department of Regenerative Medicine Science, Tokai University School of Medicine, Isehara, Japan.

Author notes

[∗ ]Correspondence: Yoshinori Sumita, Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan (e-mail: y-sumita@ 123456nagasaki-u.ac.jp ).

Author information

Yoshinori Sumita http://orcid.org/0000-0002-1247-9763

Article

Publisher ID: MD-D-20-03606 Accession ID: 20788

DOI: 10.1097/MD.0000000000020788

PMC ID: 7328916

PubMed ID: 32590759

SO-VID: bbe3d7d0-fae9-432b-aacf-e3f17720b8a4

License:

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

History

Date received : 14 May 2020

Date accepted : 21 May 2020

Funding

Funded by: Japan Agency for Medical Research and Development

Award ID: JP19bK0104069h0002

Award Recipient : Izumi Asahina

Custom metadata

OPEN-ACCESS TRUE

Keywords: cell-based therapy,macrophage,peripheral blood mononuclear cells,xerostomia

Data availability:

Keywords: cell-based therapy, macrophage, peripheral blood mononuclear cells, xerostomia

Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)

Read this article at

Abstract

Background:

Methods/design:

Discussion:

Trial registration:

Related collections

Network Medicine

Most cited references 21

A structured review and theme analysis of papers published on 'quality of life' in head and neck cancer: 2000-2005.

Concise Review: Salivary Gland Regeneration: Therapeutic Approaches from Stem Cells to Tissue Organoids

Bone marrow-derived cells rescue salivary gland function in mice with head and neck irradiation.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 236

Cited by 4

Most referenced authors 263