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Transplantation and Tracking of the Human Umbilical Cord Mesenchymal Stem Cell Labeled with Superparamagnetic Iron Oxide in Deaf Pigs
Authors:Liangwei Xu  Shuolong Yuan  Wei Chen  Yueying Ma  Yi Luo  Weiwei Guo  Shiming Yang
Affiliation:1. School of Medicine, Nankai University, Tianjin, China;2. Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China

China National Clinical Research Centre for Otolaryngologic Diseases, Beijing, China

Key Laboratory of Hearing Impairment Science of Ministry of Education, Beijing, China

Key Laboratory of Hearing Impairment Prevention and Treatment of Beijing, Beijing, China;3. Department of Otolaryngology, Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China;4. Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China

Abstract:
The purpose of this study was to establish a safe and effective approach to label the human umbilical cord mesenchymal stem cells (UC-MSCs) derived from the Wharton's Jelly with superparamagnetic iron oxide (SPIO) nanoparticles as a cell tracer. The cytotoxicity of the SPIO was screened in vitro by cytochemical experiments. The results showed the new infection protocol of SPIO-Lip2000 mixture had high efficiency and the optimal labeling concentration was a 50 μg/ml SPIO suspension. Transmission electron microscope (TEM) confirmed the distribution of the intracellular SPIO. We transplanted the labeled UC-MSCs into the sensorineural hearing loss (SNHL) minipigs at 1 week after noise exposure. Auditory brainstem response results demonstrated the transplantation of UC-MSCs was an efficient therapy for SNHL. The positive sediments in cochlear blood vessels, the bony wall of scala tympani, and spiral ganglion nerve fibers were found in the stem cell recipients' cochlea. We did not detect iron elements in the inner/outer hair cells' stereocilia, cuticular plate, or pillar cells from the basal to apex turns of the stem cell recipients' cochlea. In addition, TEM found SPIO in the medulla oblongata and the cerebrum in the SNHL minipigs after stem cell transplantation. In conclusion, we established a safe and effective approach to labeled human UC-MSCs derived from Wharton's Jelly by using SPIO nanoparticles as a cell tracer in vitro and in vivo. This protocol showed a wide promising application in stem cell therapy and tracing in vivo for experiments with large mammals. Anat Rec, 303:494–505, 2020. © 2019 American Association for Anatomy
Keywords:human umbilical cord mesenchymal stem cells  superparamagnetic iron oxide nanoparticles  cytotoxicity  stem cell therapy  sensorineural hearing loss  noise  pig
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