Stem Cells as Xerostomia Therapy Due to Ionizing Radiation

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Salivary glands are one of the normal tissues that are often negatively affected by radiation therapy, especially in the head and neck region. The radiation exposure can cause irreversible damage to the salivary glands. Damage to the salivary glands results in decreased production of saliva or hyposalivation and in a very severe condition called xerostomia. After induction of high dose radiation, irreversible hyposalivation often occurs due to the sterilization of stem cells from the primary salivary glands. Alternative therapies are needed to treat severe damage to the salivary glands. One alternative therapy that can be done is by stem cell therapy.

Several factors that influence the success of stem cell therapy include stem cells that can be firmly attached and survive in damaged areas and can integrate with the surrounding environment. However, given the low number of surviving cells, it shows the low viability of   transplanted stem cells, thereby reducing the effectiveness of the therapy. The low level of viability may be caused by conventional cell culture methods, which are carried out under normoxic conditions with a concentration of 21% O 2 .

This is contrary to the in vivo environment in which stem cells originate, which have hypoxic conditions with concentrations of 1 to 7% O 2, depending on the location and type of stem cells. Based on this description, the purpose of this study was to determine the regeneration process of salivary glands damaged by exposure to high-dose ionizing radiation with bone marrow mesenchyme stem cell transplants (BM-MSCs) that had been given hypoxic preconditions with a concentration of 1% O 2.

Method and Results

This research is an experimental analytic study. Stem cell culture was carried out under normoxic (O 2 : 21%) and hypoxic conditions by incubating cells for 48 hours in a low oxygen pressure chamber consisting of 95% N 2 , 5% CO 2 , and 1% O 2 . Thirty male Wistar rats were divided into four groups: two control groups and two treatment groups. A single dose of 15 Gy of radiation was given to the ventral neck area in all treatment groups to damage the salivary glands. Stem cell transplantation (BM-MSC) was carried out in the normoxic and hypoxic treatment group 24 hours after radiation.

The results showed significant differences in the expression of SDF1-CXCR4, Bcl-2 and also α-amylase enzyme activity in all hypoxic groups. SDF1-CXCR4 binding has an important role in increasing the ability of stem cells to migrate to damaged areas and inducing endogenous stem cells to multiply and differentiate into desirable cells. Bcl-2 is an anti-apoptotic protein that plays a role in cell survival. Hypoxia also increases the activity of the α-amylase enzyme as a marker of the regeneration process in salivary gland tissue.

The study concluded that stem cells (BM-MSCs) which have been given hypoxic preconditions have better therapeutic abilities to induce tissue repair processes than stem cells in normoxic condition.

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Author: Dr. Sri Wigati Mardi Mulyani, drg., M.Kes

Details of this research available at:

https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0039-1694697.pdf

Author: Dr. Sri Wigati Mardi Mulyani, drg., M. Kes Detailed information from this research can be seen in our writing at https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0039-1694697.pdf Mulyani SWM, Astuti ER, Wahyuni OR, Ernawati DS, Ramadhani NF. 2019. Xerostomia Therapy Due to Ionized Radiation Using Preconditioned Bone Marrow-Derived Mesenchymal Stem Cells. Eur J Dent 2019; 13 (02): 238-242.

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