Hypoxia, a dynamic tool to amplify the gingival mesenchymal stem cells potential for neurotrophic factor secretion

Shankargouda Patil; Hytham N Fageeh; Hammam Ibrahim Fageeh; Wael Ibraheem; Abdulrahman Saleh Alshehri; Ashraf Al-Brakati; Salem Almoammar; Mohammad Almagbol; Harisha Dewan; Samar Saeed Khan; Hosam Ali Baeshen; Vikrant R Patil; A Thirumal Raj; Shilpa Bhandi

doi:10.1016/j.sjbs.2022.02.039

Hypoxia, a dynamic tool to amplify the gingival mesenchymal stem cells potential for neurotrophic factor secretion

Saudi J Biol Sci. 2022 May;29(5):3568-3576. doi: 10.1016/j.sjbs.2022.02.039. Epub 2022 Feb 26.

Affiliations

¹ Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan, Saudi Arabia.
² Department of Preventive Dental Sciences, College of Dentistry, Jazan University, Jazan, Saudi Arabia.
³ Department of Human Anatomy, College of Medicine, Taif University, Taif, Saudi Arabia.
⁴ Department of Pediatric Dentistry and Orthodontics, College of Dentistry, King Khalid University, Abha, Saudi Arabia.
⁵ Department of Communirty and Eriodontics, Faculty of Dentistry, King Khalid University, Abha, Saudi Arabia.
⁶ Department of Prosthetic Dental Sciences, College of Dentistry, Jazan University, Jazan, Saudi Arabia.
⁷ Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry Jazan University, Jazan, Saudi Arabia.
⁸ Department of Orthodontics, College of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
⁹ Biogenre Private Limited, Pune, India.
¹⁰ Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai, India.
¹¹ Department of Restorative Dental Science, Division of Operative Dentistry, College of Dentistry, Jazan University, Jazan, Saudi Arabia.

Abstract

Gingival mesenchymal stem cells (GMSCs) have significant regenerative potential. Their potential applications range from the treatment of inflammatory diseases, wound healing, and oral disorders. Preconditioning these stem cells can optimize their biological properties. Hypoxia preconditioning of MSCs improves stem cell properties like proliferation, survival, and differentiation potential. This research explored the possible impact of hypoxia on the pluripotent stem cell properties that GMSCs possess. We evaluated the morphology, stemness, neurotrophic factors, and stemness-related genes. We compared the protein levels of secreted neurotrophic factors between normoxic and hypoxic GMSC-conditioned media (GMSC-CM). Results revealed that hypoxic cultured GMSC's had augmented expression of neurotrophic factors BDNF, GDNF, VEGF, and IGF1 and stemness-related gene NANOG. Hypoxic GMSCs showed decreased expression of the OCT4 gene. In hypoxic GMSC-CM, the neurotrophic factors secretions were significantly higher than normoxic GMSC-CM. Our data demonstrate that culturing of GMSCs in hypoxia enhances the secretion of neurotrophic factors that can lead to neuronal lineage differentiation.

Keywords: Gingival mesenchymal stem cell; Hypoxia; Neurotrophic factors; Normoxia.