title: Chondrogenic potential and anti-senescence effect of hypoxia on canine adipose mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) have the ability to differentiate into multi-lineage cells, which confers great promise for use in regenerative medicine. In this study, canine adipose MSCs (cAD-MSCs) were isolated from canine adipose tissue. These cells clearly represented stemness (Oct4, Sox2, and Nanog) and differentiation potential into the mesoderm (adipocytes, chondrocytes, and osteoblasts) at early passages. The aim of this study was to evaluate the effects of hypoxia on the differentiation potential into mesoderm, and the expression of anti-apoptotic genes associated with cell survival for the optimal culturing of MSCs. We observed that the proliferation of the cAD-MSCs meaningfully increased when cultured under hypoxic condition than in normoxic condition, during 7 consecutive passages. Also, we found that hypoxia strongly expressed anti-senescence related genes such as HDAC1 (histone deacetylase 1), DNMT1 (DNA (cytosine-5)-methyltransferase 1), Bcl-2 (inhibitor of apoptosis), TERT (telomerase reverse transcriptase), LDHA (lactate dehydrogenase A), SLC2A1 (glucose transporter), and DKC1 (telomere holoenzyme complex) and differentiation potential of cAD-MSCs into chondrocytes, than seen under the normoxic culture conditions. We also examined the multipotency of hypoxic conditioned MSCs using quantitative real-time RT-PCR. We found that the expression levels of stemness genes such as Oct-4, Nanog, and Sox-2 were increased in hypoxic condition when compared to the normoxic condition. Collectively, these results suggest that hypoxic conditions have the ability to induce proliferation of MSCs and augment their chondrogenic potential. This study suggests that cell proliferation of cAD-MSC under hypoxia could be beneficial, when considering these cells for cell therapies of canine bone diseases.
authors.affiliation: Animal Stem Cells Laboratory, Viral Disease Division, Animal and Plant Quarantine Agency, 175 Anyang-ro, Manan-gu, Anyang-si, Gyeonggi-do, 14089, Republic of Korea.
authors.forename: Jienny
authors.initials: J
authors.lastname: Lee
authors.affiliation: Animal Stem Cells Laboratory, Viral Disease Division, Animal and Plant Quarantine Agency, 175 Anyang-ro, Manan-gu, Anyang-si, Gyeonggi-do, 14089, Republic of Korea.
authors.forename: Jeong Su
authors.initials: JS
authors.lastname: Byeon
authors.affiliation: Animal Stem Cells Laboratory, Viral Disease Division, Animal and Plant Quarantine Agency, 175 Anyang-ro, Manan-gu, Anyang-si, Gyeonggi-do, 14089, Republic of Korea.
authors.forename: Keum Sil
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Animal Stem Cells Laboratory, Viral Disease Division, Animal and Plant Quarantine Agency, 175 Anyang-ro, Manan-gu, Anyang-si, Gyeonggi-do, 14089, Republic of Korea.
authors.forename: Na-Yeon
authors.initials: NY
authors.lastname: Gu
authors.affiliation: Animal Stem Cells Laboratory, Viral Disease Division, Animal and Plant Quarantine Agency, 175 Anyang-ro, Manan-gu, Anyang-si, Gyeonggi-do, 14089, Republic of Korea.
authors.forename: Gyeong Been
authors.initials: GB
authors.lastname: Lee
authors.affiliation: Animal Stem Cells Laboratory, Viral Disease Division, Animal and Plant Quarantine Agency, 175 Anyang-ro, Manan-gu, Anyang-si, Gyeonggi-do, 14089, Republic of Korea.
authors.forename: Hee-Ryang
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Animal Stem Cells Laboratory, Viral Disease Division, Animal and Plant Quarantine Agency, 175 Anyang-ro, Manan-gu, Anyang-si, Gyeonggi-do, 14089, Republic of Korea.
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Cho
authors.affiliation: Animal Stem Cells Laboratory, Viral Disease Division, Animal and Plant Quarantine Agency, 175 Anyang-ro, Manan-gu, Anyang-si, Gyeonggi-do, 14089, Republic of Korea. virusmania@korea.kr.
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Cha
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D004285:Dogs; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors
keywords: Canine; Differentiation; Hypoxia; Mesenchymal stem cells; Proliferation