Systemic transplantation of human adipose tissue-derived mesenchymal stem cells for the regeneration of irradiation-induced salivary gland damage.
OBJECTIVE
Cell-based therapy has been reported to repair or restore damaged salivary gland (SG) tissue after irradiation. This study was aimed at determining whether systemic administration of human adipose-derived mesenchymal stem cells (hAdMSCs) can ameliorate radiation-induced SG damage.


METHODS
hAdMSCs (1 × 10(6)) were administered through a tail vein of C3H mice immediately after local irradiation, and then this infusion was repeated once a week for 3 consecutive weeks. At 12 weeks after irradiation, functional evaluations were conducted by measuring salivary flow rates (SFRs) and salivation lag times, and histopathologic and immunofluorescence histochemistry studies were performed to assay microstructural changes, apoptosis, and proliferation indices. The engraftment and in vivo differentiation of infused hAdMSCs were also investigated, and the transdifferentiation of hAdMSCs into amylase-producing SG epithelial cells (SGCs) was observed in vitro using a co-culture system.


RESULTS
The systemic administration of hAdMSCs exhibited improved SFRs at 12 weeks after irradiation. hAdMSC-transplanted SGs showed fewer damaged and atrophied acinar cells and higher mucin and amylase production levels than untreated irradiated SGs. Immunofluorescence TUNEL assays revealed fewer apoptotic cells in the hAdMSC group than in the untreated group. Infused hAdMSCs were detected in transplanted SGs at 4 weeks after irradiation and some cells were found to have differentiated into SGCs. In vitro, a low number of co-cultured hAdMSCs (13%-18%) were observed to transdifferentiate into SGCs.


CONCLUSIONS
The findings of this study indicate that hAdMSCs have the potential to protect against irradiation-induced cell loss and to transdifferentiate into SGCs, and suggest that hAdMSC administration should be viewed as a candidate therapy for the treatment of radiation-induced SG damage.
Department of Otorhinolaryngology - Head and Neck Surgery, Inha University School of Medicine, Incheon, Republic of Korea.
Jae-Yol
JY
Lim
Jeong Chan
JC
Ra
Il Seob
IS
Shin
Yun Ho
YH
Jang
Hye-Young
HY
An
Jeong-Seok
JS
Choi
Woo Cheol
WC
Kim
Young-Mo
YM
Kim
D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D007275:Injections, Intravenous; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000628:therapy*; D012038:Regeneration; D012469:Salivary Glands / Q000473:pathology / Q000528:radiation effects*; D012472:Salivation / Q000502:physiology; D014183:Transplantation, Heterologous; D014965:X-Rays / Q000009:adverse effects