Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients

Charlotte Duch Lynggaard; Rosa Jersie-Christensen; Morten Juhl; Siri Beier Jensen; Christian Grønhøj; Jacob Melchiors; Søren Jacobsen; Michael Møller-Hansen; Mikkel Herly; Annette Ekblond; Jens Kastrup; Anne Fischer-Nielsen; Daniel Belstrøm; Christian von Buchwald

doi:10.1038/s43856-022-00223-3

Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients

Charlotte Duch Lynggaard^*, Rosa Jersie-Christensen, Morten Juhl, Siri Beier Jensen, Christian Grønhøj, Jacob Melchiors, Søren Jacobsen, Michael Møller-Hansen, Mikkel Herly, Annette Ekblond, Jens Kastrup, Anne Fischer-Nielsen, Daniel Belstrøm, Christian von Buchwald

^*Corresponding author for this work

Department of Dentistry and Oral Health - Institutledelsen, Odontologi og Oral Sundhed

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

6 Citations (Scopus)

Abstract

BACKGROUND: Hyposalivation and xerostomia (dry mouth), are the leading site-effects to treatment of head and neck cancer. Currently, there are no effective therapies to alleviate radiation-induced hyposalivation. Adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) have shown potential for restoring salivary gland function. However, the mode of action is unknown. The purpose of the present study was therefore to characterize the effect of AT-MSC therapy on the salivary proteome in previously irradiated head and neck cancer patients.

METHODS: Whole saliva was collected from patients with radiation-induced salivary gland hypofunction (n = 8) at baseline, and 120 days after AT-MSC treatment, and from healthy controls (n = 10). The salivary proteome was characterized with mass spectrometry based proteomics, and data was compared within the AT-MSC group (baseline versus day 120) and between AT-MSC group and healthy controls. Significance levels between groups were determined by using double-sided t-test, and visualized by means of principal component analysis, volcano plots and cluster analysis.

RESULTS: Here we show that 140 human proteins are significantly differentially expressed in saliva from patients with radiation-induced hypofunction versus healthy controls. AT-MSC treatment induce a significant impact on the salivary proteome, as 99 proteins are differentially expressed at baseline vs. 120 days after treatment. However, AT-MSC treatment does not restore healthy conditions, as 212 proteins are significantly differentially expressed in saliva 120 days after AT-MSCs treatment, as compared to healthy controls.

CONCLUSION: The results indicate an increase in proteins related to tissue regeneration in AT-MSCs treated patients. Our study demonstrates the impact of AT-MSCs on the salivary proteome, thereby providing insight into the potential mode of action of this novel treatment approach.

Original language	English
Article number	160
Journal	Communications Medicine
Volume	2
Issue	1
Number of pages	12
ISSN	2730-664X
DOIs	https://doi.org/10.1038/s43856-022-00223-3
Publication status	Published - Dec 2022

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Lynggaard, C. D., Jersie-Christensen, R., Juhl, M., Jensen, S. B., Grønhøj, C., Melchiors, J., Jacobsen, S., Møller-Hansen, M., Herly, M., Ekblond, A., Kastrup, J., Fischer-Nielsen, A., Belstrøm, D., & von Buchwald, C. (2022). Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients. Communications Medicine, 2(1), Article 160. https://doi.org/10.1038/s43856-022-00223-3

@article{eeefb48a5a574f1faed3cc31af4cf376,

title = "Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients",

abstract = "BACKGROUND: Hyposalivation and xerostomia (dry mouth), are the leading site-effects to treatment of head and neck cancer. Currently, there are no effective therapies to alleviate radiation-induced hyposalivation. Adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) have shown potential for restoring salivary gland function. However, the mode of action is unknown. The purpose of the present study was therefore to characterize the effect of AT-MSC therapy on the salivary proteome in previously irradiated head and neck cancer patients.METHODS: Whole saliva was collected from patients with radiation-induced salivary gland hypofunction (n = 8) at baseline, and 120 days after AT-MSC treatment, and from healthy controls (n = 10). The salivary proteome was characterized with mass spectrometry based proteomics, and data was compared within the AT-MSC group (baseline versus day 120) and between AT-MSC group and healthy controls. Significance levels between groups were determined by using double-sided t-test, and visualized by means of principal component analysis, volcano plots and cluster analysis.RESULTS: Here we show that 140 human proteins are significantly differentially expressed in saliva from patients with radiation-induced hypofunction versus healthy controls. AT-MSC treatment induce a significant impact on the salivary proteome, as 99 proteins are differentially expressed at baseline vs. 120 days after treatment. However, AT-MSC treatment does not restore healthy conditions, as 212 proteins are significantly differentially expressed in saliva 120 days after AT-MSCs treatment, as compared to healthy controls.CONCLUSION: The results indicate an increase in proteins related to tissue regeneration in AT-MSCs treated patients. Our study demonstrates the impact of AT-MSCs on the salivary proteome, thereby providing insight into the potential mode of action of this novel treatment approach.",

author = "Lynggaard, {Charlotte Duch} and Rosa Jersie-Christensen and Morten Juhl and Jensen, {Siri Beier} and Christian Gr{\o}nh{\o}j and Jacob Melchiors and S{\o}ren Jacobsen and Michael M{\o}ller-Hansen and Mikkel Herly and Annette Ekblond and Jens Kastrup and Anne Fischer-Nielsen and Daniel Belstr{\o}m and {von Buchwald}, Christian",

year = "2022",

month = dec,

doi = "10.1038/s43856-022-00223-3",

language = "English",

volume = "2",

journal = "Communications Medicine",

issn = "2730-664X",

publisher = "Springer Nature",

number = "1",

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Lynggaard, CD, Jersie-Christensen, R, Juhl, M, Jensen, SB, Grønhøj, C, Melchiors, J, Jacobsen, S, Møller-Hansen, M, Herly, M, Ekblond, A, Kastrup, J, Fischer-Nielsen, A, Belstrøm, D & von Buchwald, C 2022, 'Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients', Communications Medicine, vol. 2, no. 1, 160. https://doi.org/10.1038/s43856-022-00223-3

Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients. / Lynggaard, Charlotte Duch; Jersie-Christensen, Rosa; Juhl, Morten et al.
In: Communications Medicine, Vol. 2, No. 1, 160, 12.2022.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients

AU - Lynggaard, Charlotte Duch

AU - Jersie-Christensen, Rosa

AU - Juhl, Morten

AU - Jensen, Siri Beier

AU - Grønhøj, Christian

AU - Melchiors, Jacob

AU - Jacobsen, Søren

AU - Møller-Hansen, Michael

AU - Herly, Mikkel

AU - Ekblond, Annette

AU - Kastrup, Jens

AU - Fischer-Nielsen, Anne

AU - Belstrøm, Daniel

AU - von Buchwald, Christian

PY - 2022/12

Y1 - 2022/12

N2 - BACKGROUND: Hyposalivation and xerostomia (dry mouth), are the leading site-effects to treatment of head and neck cancer. Currently, there are no effective therapies to alleviate radiation-induced hyposalivation. Adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) have shown potential for restoring salivary gland function. However, the mode of action is unknown. The purpose of the present study was therefore to characterize the effect of AT-MSC therapy on the salivary proteome in previously irradiated head and neck cancer patients.METHODS: Whole saliva was collected from patients with radiation-induced salivary gland hypofunction (n = 8) at baseline, and 120 days after AT-MSC treatment, and from healthy controls (n = 10). The salivary proteome was characterized with mass spectrometry based proteomics, and data was compared within the AT-MSC group (baseline versus day 120) and between AT-MSC group and healthy controls. Significance levels between groups were determined by using double-sided t-test, and visualized by means of principal component analysis, volcano plots and cluster analysis.RESULTS: Here we show that 140 human proteins are significantly differentially expressed in saliva from patients with radiation-induced hypofunction versus healthy controls. AT-MSC treatment induce a significant impact on the salivary proteome, as 99 proteins are differentially expressed at baseline vs. 120 days after treatment. However, AT-MSC treatment does not restore healthy conditions, as 212 proteins are significantly differentially expressed in saliva 120 days after AT-MSCs treatment, as compared to healthy controls.CONCLUSION: The results indicate an increase in proteins related to tissue regeneration in AT-MSCs treated patients. Our study demonstrates the impact of AT-MSCs on the salivary proteome, thereby providing insight into the potential mode of action of this novel treatment approach.

AB - BACKGROUND: Hyposalivation and xerostomia (dry mouth), are the leading site-effects to treatment of head and neck cancer. Currently, there are no effective therapies to alleviate radiation-induced hyposalivation. Adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) have shown potential for restoring salivary gland function. However, the mode of action is unknown. The purpose of the present study was therefore to characterize the effect of AT-MSC therapy on the salivary proteome in previously irradiated head and neck cancer patients.METHODS: Whole saliva was collected from patients with radiation-induced salivary gland hypofunction (n = 8) at baseline, and 120 days after AT-MSC treatment, and from healthy controls (n = 10). The salivary proteome was characterized with mass spectrometry based proteomics, and data was compared within the AT-MSC group (baseline versus day 120) and between AT-MSC group and healthy controls. Significance levels between groups were determined by using double-sided t-test, and visualized by means of principal component analysis, volcano plots and cluster analysis.RESULTS: Here we show that 140 human proteins are significantly differentially expressed in saliva from patients with radiation-induced hypofunction versus healthy controls. AT-MSC treatment induce a significant impact on the salivary proteome, as 99 proteins are differentially expressed at baseline vs. 120 days after treatment. However, AT-MSC treatment does not restore healthy conditions, as 212 proteins are significantly differentially expressed in saliva 120 days after AT-MSCs treatment, as compared to healthy controls.CONCLUSION: The results indicate an increase in proteins related to tissue regeneration in AT-MSCs treated patients. Our study demonstrates the impact of AT-MSCs on the salivary proteome, thereby providing insight into the potential mode of action of this novel treatment approach.

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U2 - 10.1038/s43856-022-00223-3

DO - 10.1038/s43856-022-00223-3

M3 - Journal article

C2 - 36496530

SN - 2730-664X

VL - 2

JO - Communications Medicine

JF - Communications Medicine

IS - 1

M1 - 160

ER -

Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients

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