Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy

Bone fractures and bone loss represent significant global health challenges, with their incidence rising due to an aging population. Despite autologous bone grafts remain the gold standard for treatment, challenges such as limited bone availability, immune reactions, and the risk of infectious disea...

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Main Authors: Hemanathan Vembuli, Sheeja Rajasingh, Patrick Nabholz, Jefferson Guenther, Brian R. Morrow, Margaret M. Taylor, Marziyeh Aghazadeh, Vinoth Sigamani, Johnson Rajasingh
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Experimental Biology and Medicine
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Online Access:https://www.ebm-journal.org/articles/10.3389/ebm.2025.10342/full
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author Hemanathan Vembuli
Sheeja Rajasingh
Patrick Nabholz
Jefferson Guenther
Brian R. Morrow
Margaret M. Taylor
Marziyeh Aghazadeh
Vinoth Sigamani
Johnson Rajasingh
Johnson Rajasingh
Johnson Rajasingh
author_facet Hemanathan Vembuli
Sheeja Rajasingh
Patrick Nabholz
Jefferson Guenther
Brian R. Morrow
Margaret M. Taylor
Marziyeh Aghazadeh
Vinoth Sigamani
Johnson Rajasingh
Johnson Rajasingh
Johnson Rajasingh
author_sort Hemanathan Vembuli
collection DOAJ
description Bone fractures and bone loss represent significant global health challenges, with their incidence rising due to an aging population. Despite autologous bone grafts remain the gold standard for treatment, challenges such as limited bone availability, immune reactions, and the risk of infectious disease transmission have driven the search for alternative cell-based therapies for bone regeneration. Stem cells derived from oral tissues and umbilical cord mesenchymal stem cells (MSCs) have shown potential in both preclinical and clinical studies for bone tissue regeneration. However, their limited differentiation capacity and wound healing abilities necessitate the exploration of alternative cell sources. In this study, we generated induced pluripotent stem cells (iPSCs) using a safe, nonviral and mRNA-based approach from human periodontal ligament fibroblasts (PDLF), an easily accessible cell source. These iPSCs were subsequently differentiated into MSCs, referred to as induced MSCs (iMSCs). The resulting iMSCs were homogeneous, highly proliferative, and possessed anti-inflammatory properties, suggesting their potential as a superior alternative to traditional MSCs for regenerative therapy. These iMSCs demonstrated trilineage differentiation potential, giving rise to osteocytes, chondrocytes, and adipocytes. The iMSC-derived osteocytes (iOSTs) were homogeneous, patient-specific and showed excellent attachment and growth on commercial collagen-based membranes, highlighting their suitability for bone tissue regeneration applications. Given their promising characteristics compared to traditional MSCs, PDLF-derived iMSCs are strong candidates for future clinical studies in bone regeneration and other regenerative dental therapies.
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spelling doaj-art-fa45d7415b044db583a7a9e6c298af882025-02-03T04:10:58ZengFrontiers Media S.A.Experimental Biology and Medicine1535-36992025-02-0125010.3389/ebm.2025.1034210342Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapyHemanathan Vembuli0Sheeja Rajasingh1Patrick Nabholz2Jefferson Guenther3Brian R. Morrow4Margaret M. Taylor5Marziyeh Aghazadeh6Vinoth Sigamani7Johnson Rajasingh8Johnson Rajasingh9Johnson Rajasingh10Department of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Medicine-Cardiology, University of Tennessee Health Science Center, Memphis, TN, United StatesDepartment of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, United StatesBone fractures and bone loss represent significant global health challenges, with their incidence rising due to an aging population. Despite autologous bone grafts remain the gold standard for treatment, challenges such as limited bone availability, immune reactions, and the risk of infectious disease transmission have driven the search for alternative cell-based therapies for bone regeneration. Stem cells derived from oral tissues and umbilical cord mesenchymal stem cells (MSCs) have shown potential in both preclinical and clinical studies for bone tissue regeneration. However, their limited differentiation capacity and wound healing abilities necessitate the exploration of alternative cell sources. In this study, we generated induced pluripotent stem cells (iPSCs) using a safe, nonviral and mRNA-based approach from human periodontal ligament fibroblasts (PDLF), an easily accessible cell source. These iPSCs were subsequently differentiated into MSCs, referred to as induced MSCs (iMSCs). The resulting iMSCs were homogeneous, highly proliferative, and possessed anti-inflammatory properties, suggesting their potential as a superior alternative to traditional MSCs for regenerative therapy. These iMSCs demonstrated trilineage differentiation potential, giving rise to osteocytes, chondrocytes, and adipocytes. The iMSC-derived osteocytes (iOSTs) were homogeneous, patient-specific and showed excellent attachment and growth on commercial collagen-based membranes, highlighting their suitability for bone tissue regeneration applications. Given their promising characteristics compared to traditional MSCs, PDLF-derived iMSCs are strong candidates for future clinical studies in bone regeneration and other regenerative dental therapies.https://www.ebm-journal.org/articles/10.3389/ebm.2025.10342/fullmesenchymal stem cellsinduced pluripotent stem cellsdifferentiationosteocytesregenerative therapy
spellingShingle Hemanathan Vembuli
Sheeja Rajasingh
Patrick Nabholz
Jefferson Guenther
Brian R. Morrow
Margaret M. Taylor
Marziyeh Aghazadeh
Vinoth Sigamani
Johnson Rajasingh
Johnson Rajasingh
Johnson Rajasingh
Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy
Experimental Biology and Medicine
mesenchymal stem cells
induced pluripotent stem cells
differentiation
osteocytes
regenerative therapy
title Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy
title_full Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy
title_fullStr Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy
title_full_unstemmed Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy
title_short Induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy
title_sort induced mesenchymal stem cells generated from periodontal ligament fibroblast for regenerative therapy
topic mesenchymal stem cells
induced pluripotent stem cells
differentiation
osteocytes
regenerative therapy
url https://www.ebm-journal.org/articles/10.3389/ebm.2025.10342/full
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