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1.
Sci Adv ; 8(25): eabm6504, 2022 06 24.
Article in English | MEDLINE | ID: mdl-35749495

ABSTRACT

Aging has been reported to deteriorate the quantity and quality of mesenchymal stem cells (MSCs), which affect their therapeutic use in regenerative medicine. A dearth of age-related stem cell research further restricts their clinical applications. The present study explores the possibility of using MSCs derived from human gingival tissues (GMSCs) for studying their ex vivo growth characteristics and differentiation potential with respect to donor age. GMSCs displayed decreased in vitro adipogenesis and in vitro and in vivo osteogenesis with age, but in vitro neurogenesis remained unaffected. An increased expression of p53 and SIRT1 with donor age was correlated to their ability of eliminating tumorigenic events through apoptosis or autophagy, respectively. Irrespective of donor age, GMSCs displayed effective immunoregulation and regenerative potential in a mouse model of LPS-induced acute lung injury. Thus, we suggest the potential of GMSCs for designing cell-based immunomodulatory therapeutic approaches and their further extrapolation for acute inflammatory conditions such as acute respiratory distress syndrome and COVID-19.


Subject(s)
COVID-19 , Mesenchymal Stem Cells , Animals , Cell Differentiation , Gingiva , Humans , Mesenchymal Stem Cells/metabolism , Mice , Osteogenesis
2.
Nanomedicine ; 15(1): 218-230, 2019 01.
Article in English | MEDLINE | ID: mdl-30343014

ABSTRACT

Parathyroid hormone (PTH) has been a major contributor to the anabolic therapy for osteoporosis, but its delivery to bone without losing activity and avoiding adverse local effects remain a challenge. Being the natural component of bone, use of hydroxyapatite for this purpose brings a major breakthrough in synergistic anabolism. This study focuses on synthesis, characterization and evaluation of in vitro and in vivo efficacy of PTH (1-34) adsorbed hydroxyapatite nanocarrier for synergistic enhancement in the anabolic activity of PTH for bone regeneration. The negative zeta potential of this nanocarrier facilitated its affinity to the Ca2+ rich bone tissue and solubilization at low pH enhanced specific delivery of PTH to the resorption pits in osteoporotic bone. In this process, PTH retained its anabolic effect and at the same time an increase in bone mineral content indicated enhancement of the net formative effect of the PTH anabolic therapy.


Subject(s)
Anabolic Agents/administration & dosage , Bone Regeneration , Calcium-Regulating Hormones and Agents/administration & dosage , Durapatite/chemistry , Nanotubes/chemistry , Osteoporosis/drug therapy , Parathyroid Hormone/administration & dosage , Animals , Apoptosis , Cell Proliferation , Cells, Cultured , Female , Mice , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoporosis/metabolism , Ovariectomy
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