Dental pulp stem cells promote genioglossus repair and systemic amelioration in chronic intermittent hypoxia

Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSC...

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Published iniScience Vol. 27; no. 11; p. 111143
Main Authors Zhang, Meng-Han, Zhang, Wei-Hua, Lu, Yun, Yu, Li-Ming, Han, Xin-Xin, Xu, Yan, Wu, Meng-Jie, Ding, Wang-Hui, Liu, Yue-Hua
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 15.11.2024
Elsevier
Subjects
Cell biology
Molecular biology
Stem cells research
Cell biology
Molecular biology
Stem cells research
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Abstract Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model. We induced DPSCs to myogenic lineage cells (iDPSCs) and transplanted them into GG of CIH mice. DPSCs/iDPSCs grafts improved EMGGG and muscle type transitions while reducing tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, improving body weight. Moreover, iDPSCs increased Pax7+/Ki67+ and human-derived STEM121 cells in the GG compared with DPSCs. DPSCs/iDPSCs enhanced Desmin+ myotube formation in myoblasts under hypoxia in vitro, with iDPSCs increased human-derived myogenic markers and nuclei in myotubes. These results indicate that iDPSCs, beyond their paracrine effects like DPSCs, directly participate in myogenic differentiation, supporting the potential use of DPSCs for OSA treatment. [Display omitted] •DPSCs/iDPSCs improve EMGGG, muscle fiber type transition, systemic inflammation in CIH mice•iDPSCs enhance GG repair in CIH mice by elevating expression of MyoD and Pax7 vs. DPSCs•Both DPSCs and iDPSCs promote muscle regeneration via paracrine effects•iDPSCs directly aid myogenic differentiation, seen human-derived myogenic transcripts Molecular biology; Cell biology; Stem cells research
AbstractList Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model. We induced DPSCs to myogenic lineage cells (iDPSCs) and transplanted them into GG of CIH mice. DPSCs/iDPSCs grafts improved EMGGG and muscle type transitions while reducing tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, improving body weight. Moreover, iDPSCs increased Pax7+/Ki67+ and human-derived STEM121 cells in the GG compared with DPSCs. DPSCs/iDPSCs enhanced Desmin+ myotube formation in myoblasts under hypoxia in vitro, with iDPSCs increased human-derived myogenic markers and nuclei in myotubes. These results indicate that iDPSCs, beyond their paracrine effects like DPSCs, directly participate in myogenic differentiation, supporting the potential use of DPSCs for OSA treatment. [Display omitted] •DPSCs/iDPSCs improve EMGGG, muscle fiber type transition, systemic inflammation in CIH mice•iDPSCs enhance GG repair in CIH mice by elevating expression of MyoD and Pax7 vs. DPSCs•Both DPSCs and iDPSCs promote muscle regeneration via paracrine effects•iDPSCs directly aid myogenic differentiation, seen human-derived myogenic transcripts Molecular biology; Cell biology; Stem cells research
Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model. We induced DPSCs to myogenic lineage cells (iDPSCs) and transplanted them into GG of CIH mice. DPSCs/iDPSCs grafts improved EMG and muscle type transitions while reducing tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, improving body weight. Moreover, iDPSCs increased Pax7 /Ki67 and human-derived STEM121 cells in the GG compared with DPSCs. DPSCs/iDPSCs enhanced Desmin myotube formation in myoblasts under hypoxia , with iDPSCs increased human-derived myogenic markers and nuclei in myotubes. These results indicate that iDPSCs, beyond their paracrine effects like DPSCs, directly participate in myogenic differentiation, supporting the potential use of DPSCs for OSA treatment.
Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model. We induced DPSCs to myogenic lineage cells (iDPSCs) and transplanted them into GG of CIH mice. DPSCs/iDPSCs grafts improved EMGGG and muscle type transitions while reducing tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, improving body weight. Moreover, iDPSCs increased Pax7+/Ki67+ and human-derived STEM121 cells in the GG compared with DPSCs. DPSCs/iDPSCs enhanced Desmin+ myotube formation in myoblasts under hypoxia in vitro, with iDPSCs increased human-derived myogenic markers and nuclei in myotubes. These results indicate that iDPSCs, beyond their paracrine effects like DPSCs, directly participate in myogenic differentiation, supporting the potential use of DPSCs for OSA treatment.Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model. We induced DPSCs to myogenic lineage cells (iDPSCs) and transplanted them into GG of CIH mice. DPSCs/iDPSCs grafts improved EMGGG and muscle type transitions while reducing tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, improving body weight. Moreover, iDPSCs increased Pax7+/Ki67+ and human-derived STEM121 cells in the GG compared with DPSCs. DPSCs/iDPSCs enhanced Desmin+ myotube formation in myoblasts under hypoxia in vitro, with iDPSCs increased human-derived myogenic markers and nuclei in myotubes. These results indicate that iDPSCs, beyond their paracrine effects like DPSCs, directly participate in myogenic differentiation, supporting the potential use of DPSCs for OSA treatment.
Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model. We induced DPSCs to myogenic lineage cells (iDPSCs) and transplanted them into GG of CIH mice. DPSCs/iDPSCs grafts improved EMGGG and muscle type transitions while reducing tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, improving body weight. Moreover, iDPSCs increased Pax7+/Ki67+ and human-derived STEM121 cells in the GG compared with DPSCs. DPSCs/iDPSCs enhanced Desmin+ myotube formation in myoblasts under hypoxia in vitro, with iDPSCs increased human-derived myogenic markers and nuclei in myotubes. These results indicate that iDPSCs, beyond their paracrine effects like DPSCs, directly participate in myogenic differentiation, supporting the potential use of DPSCs for OSA treatment.
ArticleNumber 111143
Author Zhang, Wei-Hua
Xu, Yan
Ding, Wang-Hui
Wu, Meng-Jie
Yu, Li-Ming
Zhang, Meng-Han
Lu, Yun
Han, Xin-Xin
Liu, Yue-Hua
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Snippet Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest...
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SubjectTerms Cell biology
Molecular biology
Stem cells research
Title Dental pulp stem cells promote genioglossus repair and systemic amelioration in chronic intermittent hypoxia
URI https://dx.doi.org/10.1016/j.isci.2024.111143
https://www.ncbi.nlm.nih.gov/pubmed/39524365
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Volume 27
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