Safety and Efficacy of Mesenchymal Stem Cells for Radiation-Induced Xerostomia: A Randomized, Placebo-Controlled Phase 1/2 Trial (MESRIX)

Grønhøj, Christian; Jensen, David Hebbelstrup; Vester-Glowinski, Peter; Jensen, Siri Beier; Bardow, Allan; Oliveri, Roberto S; Munthe-Fog, Lea; Specht, Lena; Thomsen, Carsten; Darkner, Sune; Jensen, Maria; Müller, V; Kiss, Katalin; Agander, Tina Klitmøller; Andersen, Elo; Fischer‐Nielsen, Anne

doi:10.1016/j.ijrobp.2018.02.034

Cited by 88 publications

(107 citation statements)

References 26 publications

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“…MSCs derived from different sources, such as bone marrow or adipose tissue, have been associated with the regeneration of radiation-damaged normal tissues [52] including salivary glands [53,54]. A recent phase I/II clinical trial has shown the clinical feasibility and a marginal effect of such a therapy in the treatment of postradiotherapy hyposalivation [55]. However, since MSCs do not transdifferentiate into salivary gland cells but rather stimulate remaining surviving cells to proliferate, their action depends on the The left panel depicts a model of a salivary gland and shows the structure of the acinus, which when enlarged features the different cell types it is composed of.…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Prevention and treatment of radiotherapy‐induced side effects

2020

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Radiotherapy remains a mainstay of cancer treatment, being used in roughly 50% of patients. The precision with which the radiation dose can be delivered is rapidly improving. This precision allows the more accurate targeting of radiation dose to the tumor and reduces the amount of surrounding normal tissue exposed. Although this often reduces the unwanted side effects of radiotherapy, we still need to further improve patients' quality of life and to escalate radiation doses to tumors when necessary. Highprecision radiotherapy forces one to choose which organ or functional organ substructures should be spared. To be able to make such choices, we urgently need to better understand the molecular and physiological mechanisms of normal tissue responses to radiotherapy. Currently, oversimplified approaches using constraints on mean doses, and irradiated volumes of normal tissues are used to plan treatments with minimized risk of radiation side effects. In this review, we discuss the responses of three different normal tissues to radiotherapy: the salivary glands, cardiopulmonary system, and brain. We show that although they may share very similar local cellular processes, they respond very differently through organ-specific, nonlocal mechanisms. We also discuss how a better knowledge of these mechanisms can be used to treat or to prevent the effects of radiotherapy on normal tissue and to optimize radiotherapy delivery.

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Section: Therapeutic Approachesmentioning

confidence: 99%

Prevention and treatment of radiotherapy‐induced side effects

2020

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“…Radiotherapy is commonly administered in patients with head and neck cancers, although the precise dosage treatment often leads to many complications such as salivary gland hypofunction and xerostomia. Grønhøj et al found that transplantation of previously cultured ASCs could successfully restore the function of submandibular glands as compared with a placebo group [127,128]. Furthermore, stem cells are known for their possible application in chronic wound management.…”

Section: Human Clinical Trialsmentioning

confidence: 99%

“…Safety and efficacy of mesenchymal stem cells for radiation-induced xerostomia: A randomized, placebo-controlled phase 1/2 trial (MESRIX) [127] Prospective, randomized, controlled phase 1/2 trial…”

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confidence: 99%

In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

Jankowski

Dompe

Sibiak

et al. 2020

Cells

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Adipose-derived stem cells (ASCs) exhibiting mesenchymal stem cell (MSC) characteristics, have been extensively studied in recent years. Because they have been shown to differentiate into lineages such as osteogenic, chondrogenic, neurogenic or myogenic, the focus of most of the current research concerns either their potential to replace bone marrow as a readily available and abundant source of MSCs, or to employ them in regenerative and reconstructive medicine. There is close to consensus regarding the methodology used for ASC isolation and culture, whereas a number of molecular analyses implicates them in potential therapies of a number of pathologies. When it comes to clinical application, there is a range of examples of animal trials and clinical studies employing ASCs, further emphasizing the advancement of studies leading to their more widespread use. Nevertheless, in vitro studies will most likely continue to play a significant role in ASC studies, both providing the molecular knowledge of their ex vivo properties and possibly serving as an important step in purification and application of those cells in a clinical setting. Therefore, it is important to consider current methods of ASC isolation, culture, and processing. Furthermore, molecular analyses and cell surface properties of ASCs are essential for animal studies, clinical studies, and therapeutic applications of the MSC properties.

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“…Another salvage approach might be regeneration of the SGs. In a clinical trial of head and neck cancer patients after radiotherapy, ultrasound-guided transplantation of adipose tissue-derived mesenchymal stem cells to the submandibular glands for treatment of radiation-induced xerostomia achieved an increase in salivary flow of 33% after 1 mo and 50% after 4 mo (17).…”

mentioning

confidence: 99%