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Protective/restorative role of the adipose tissue-derived mesenchymal stem cells on the radioiodine-induced salivary gland damage in rats

Güleser Saylam
Güleser Saylam
, 
Ömer Bayır
Ömer Bayır
, 
Salih Sinan Gültekin
Salih Sinan Gültekin
, 
Ferda Alparslan Pınarlı
Ferda Alparslan Pınarlı
, 
Ünsal Han
Ünsal Han
, 
Mehmet Hakan Korkmaz
Mehmet Hakan Korkmaz
, 
Mehmet Eser Sancaktar
Mehmet Eser Sancaktar
, 
İlkan Tatar
İlkan Tatar
, 
Mustafa Fevzi Sargon
Mustafa Fevzi Sargon
 and 
Emel Çadallı Tatar
Emel Çadallı Tatar
   | Jun 14, 2017
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Article Category: Research Article
Published Online: Jun 14, 2017
Page range: 307 - 316
Received: Dec 21, 2016
Accepted: Apr 07, 2017
DOI: https://doi.org/10.1515/raon-2017-0022
© 2017 Güleser Saylam, Ömer Bayır, Salih Sinan Gültekin, Ferda Alparslan Pınarlı, Ünsal Han, Mehmet Hakan Korkmaz, Mehmet Eser Sancaktar, İlkan Tatar, Mustafa Fevzi Sargon, Emel Çadallı Tatar
This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1

Histological photographs of salivary gland tissue samples. Pictures on the upper horizontal line show control groups at 1st month evaluation (A; haematoxylin and eosin (H&E)×40), and at 6th month evaluation in different magnifications (B; H&E×200, C; H&E×400). Pictures on the second horizontal line (D to F; ×200 Leica DM 1000) shows the localization of BrdU(+) Adipose Derived Mesenchimal Stem Cells (ADMSC) in the salivary gland (brown stained cells) at 1st month after its intraperitoneal injection in different magnifications. Radioiodine-induced damage in Group 1 is seen in pictures on the third horizontal line (G to I; H&E×400, H&E×400 and H&E×100). Massive vacuolization, necrosis (black arrow) and edema were shown in G minimal vacuolization (black arrow) and periductal fibrosis (black star) in H and lenfosit infiltration (black arrow) in I. Pictures on the lower horizontal line (J to L H&E×400, H&E×200 and H&E×40) indicates the improvements in the histological findings (including vacuolization, fibrosis and edema: black arrow; nearly normal mucous acini, black star; nearly normal ductal system) at 6th month evaluation after the late ADMSC administration in Group 6.
Histological photographs of salivary gland tissue samples. Pictures on the upper horizontal line show control groups at 1st month evaluation (A; haematoxylin and eosin (H&E)×40), and at 6th month evaluation in different magnifications (B; H&E×200, C; H&E×400). Pictures on the second horizontal line (D to F; ×200 Leica DM 1000) shows the localization of BrdU(+) Adipose Derived Mesenchimal Stem Cells (ADMSC) in the salivary gland (brown stained cells) at 1st month after its intraperitoneal injection in different magnifications. Radioiodine-induced damage in Group 1 is seen in pictures on the third horizontal line (G to I; H&E×400, H&E×400 and H&E×100). Massive vacuolization, necrosis (black arrow) and edema were shown in G minimal vacuolization (black arrow) and periductal fibrosis (black star) in H and lenfosit infiltration (black arrow) in I. Pictures on the lower horizontal line (J to L H&E×400, H&E×200 and H&E×40) indicates the improvements in the histological findings (including vacuolization, fibrosis and edema: black arrow; nearly normal mucous acini, black star; nearly normal ductal system) at 6th month evaluation after the late ADMSC administration in Group 6.

Figure 2

The figure (magnification × 5000) demonstrates the findings of electron microscopy at months 1 and 6. (A and B). Normal salivary gland samples of the control group. A and D. Intracellular vacuoles and intercellular edema related to radioiodine in Group 1. E and F. We observed intracellular vacuoles, intercellular edema, nucleus of fibroblast and collagen fibers (fibrosis) at 1st month evaluation in the treatment groups (Groups 5 and 6); G to J. Improvement in cellular damage at 6th month in the stem cell-administered groups (Groups 5 and 6). On the images; c: collagen fibers; e: intercellular edema; f: nucleus of fibroblast; n: nucleus, p: dilated perinuclear cistern; v: intracellular vacuoles.
The figure (magnification × 5000) demonstrates the findings of electron microscopy at months 1 and 6. (A and B). Normal salivary gland samples of the control group. A and D. Intracellular vacuoles and intercellular edema related to radioiodine in Group 1. E and F. We observed intracellular vacuoles, intercellular edema, nucleus of fibroblast and collagen fibers (fibrosis) at 1st month evaluation in the treatment groups (Groups 5 and 6); G to J. Improvement in cellular damage at 6th month in the stem cell-administered groups (Groups 5 and 6). On the images; c: collagen fibers; e: intercellular edema; f: nucleus of fibroblast; n: nucleus, p: dilated perinuclear cistern; v: intracellular vacuoles.

Figure 3

The figure represents functional data obtained from the time-activity curves of rats. A time-activity curve generated from dynamic scintigraphic data depicts the functional changing in activity of rat salivary glands over time. A baseline study (left side; A, C, E, G) and a six-month follow-up study (right side; B, D, F, H) on the rats was performed by 99mTc-pertecnetate salivary gland scintigraphy (2 mCi, 120 frames, 20 second per frame, 40 min). The functional differences between baseline and post-treatment status can be easily seen, and compared by time-activity curves. Definitions on a time-activity curve in this figure are as follows: x axis; examination time (minutes), y axis; count data (counts/second), purple line; left salivary gland activity curve, blue line; right salivary gland activity curve and red line; background tissue activity curve. (A and B). A significant deterioration in function over time with decreased gland uptake and secretion capability with only radioiodine administration (Group 1) is seen. (C to H). Radioiodine plus concomitant amifostine (Group 4; C and D), radioiodine plus concomitant (Groups 5; E and F) and after 48 h (Group 6; G and H) adipose tissue-derived mesenchymal stem cells administrations show mild to moderate deteriorations in function over time in terms of slope of the curve and secretion capability of the gland.
The figure represents functional data obtained from the time-activity curves of rats. A time-activity curve generated from dynamic scintigraphic data depicts the functional changing in activity of rat salivary glands over time. A baseline study (left side; A, C, E, G) and a six-month follow-up study (right side; B, D, F, H) on the rats was performed by 99mTc-pertecnetate salivary gland scintigraphy (2 mCi, 120 frames, 20 second per frame, 40 min). The functional differences between baseline and post-treatment status can be easily seen, and compared by time-activity curves. Definitions on a time-activity curve in this figure are as follows: x axis; examination time (minutes), y axis; count data (counts/second), purple line; left salivary gland activity curve, blue line; right salivary gland activity curve and red line; background tissue activity curve. (A and B). A significant deterioration in function over time with decreased gland uptake and secretion capability with only radioiodine administration (Group 1) is seen. (C to H). Radioiodine plus concomitant amifostine (Group 4; C and D), radioiodine plus concomitant (Groups 5; E and F) and after 48 h (Group 6; G and H) adipose tissue-derived mesenchymal stem cells administrations show mild to moderate deteriorations in function over time in terms of slope of the curve and secretion capability of the gland.

Histological findings in the salivary glands of the rats. Mean values of salivary gland damage parameters are given. *Details of groups are given below the table

Site ofdamage Investigatedparameters Control Group 1 Group 2 Group 3 Group 4 Group 5 Group 6
1st m 6th m p 1st m 6th m p 1st m 6th m p 1st m 6th m p 1st m 6th m p 1st m 6th m p 1st m 6th m p
Edema 3.67 5.5 ns 6 7.17 ns 5.67 7.67 0.05 5 5.5 ns 4.33 7 0.02 4.33 4.83 ns 5.67 3 0.02
Acinar epithelial cell damage Vacuolization 4.33 3.5 ns 6.67 6.33 ns 5 7 0.04 4.67 4.17 ns 4 5.33 ns 5 3.67 ns 5.33 2 0.02
Peri acinar inflammation 0 0 ns 0.67 0.17 ns 1.33 0.17 ns 0.67 0.17 ns 0 0.17 ns 0 0.17 ns 2 0 0.02
Necrosis 0.67 2.33 ns 0 1.33 0.04 2 0.5 ns 1.67 1 ns 0 1 ns 0.33 0 ns 0.67 0.17 ns
Ductal system damage Ectasia 3 3.33 ns 6.33 5.83 ns 4.33 6 ns 3.67 2.5 ns 2.67 4.67 0.01 3.67 3.5 ns 3.33 0.83 0.04
Periductal fibrosis 0 0 ns 1 3.33 0.02 2.33 3.33 ns 1 0.33 ns 0 2.33 0.02 0 1.33 0.01 0 0.67 ns
Interstitial space damage Periduktal sclerosis 0 0.17 ns 0 2.17 0.02 1.33 1.83 ns 1 0 0.03 0 0.33 ns 0 0.67 ns 0 0 ns
Periductal mucus leakage 1 0.5 ns 1 1 ns 0.67 1.33 ns 1.33 1 ns 0.33 0.83 ns 0.33 0.33 ns 3 0.5 0.02
Vascular system damage Sclerosis 0 0.17 ns 1 4.5 0.01 1.67 3.5 ns 1.33 0.5 ns 0.67 1.17 ns 0 1.17 0.01 1.67 0.5 ns
Total 12.67 15.5 ns 22.67 31.83 0.02 24.33 31.33 ns 20.34 15.17 0.05 12 22.83 0.02 13.66 15.67 ns 21.67 7.67 0.02

The mean values (the counts from left and right salivary glands) of the Smax, Tmax/Tmin and G/BGmax, and their statistical significance. Baseline and follow-up salivary gland scintigraphies were performed on the subjects who had single treatment (Group 1; radioiodine, Group 2; adipose tissue-derived mesenchymal stem cells, Group 3; amifostine) and combined treatments (Group 4; radioiodine plus amifostine, Group 5; radioiodine plus adipose tissue-derived mesenchymal stem cells concomitant, Group 6; radioiodine plus adipose tissue-derived mesenchymal stem cells after 48 h)

Groups Smax (%) Tmax/Tmin G/BGmax
Baseline 1st m 6th m p Baseline 1st m 6th m p Baseline 1st m 6th m p
Group 1 34.80 29.58 19.72 0.04 0.07 0.08 0.14 0.05 1.63 1.38 1.30 0.04
Group 2 34.74 34.31 34.62 ns 0.06 0.06 0.07 ns 1.59 1.57 1.58 ns
Group 3 34.72 34.38 33.83 ns 0.08 0.08 0.09 ns 1.59 1.56 1.57 ns
Group 4 33.07 30.30 28.88 0.04 0.08 0.08 0.09 ns 1.57 1.49 1.44 0.04
Group 5 33.51 32.91 28.89 0.04 0.08 0.08 0.09 ns 1.58 1.52 1.49 0.04
Group 6 35.55 31.60 26.07 0.04 0.07 0.07 0.09 ns 1.60 1.51 1.36 0.04
p ns 0.01 0.01 ns ns 0.03 ns 0.01 0.01
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