KMID : 1377020210180050851
|
|
Tissue Engineering and Regenerative Medicine 2021 Volume.18 No. 5 p.851 ~ p.862
|
|
Therapeutic Effect of IL1¥â Priming Tonsil Derived-Mesenchymal Stem Cells in Osteoporosis
|
|
Yoo Min-Joo
Cho Sung-Kuk Shin Sun-Hye Kim Jung-Mi Park Hyeon-Gyeong Cho Sung-Yoo Hwang Yu-Kyeong Park Dae-Hwi
|
|
Abstract
|
|
|
Background: Stem cell therapies can be a new therapeutic strategy that may rebalance anabolic and anti-resorptive effects in osteoporosis patients. Tonsil-derived mesenchymal stem cells (TMSCs) can be an alternative therapeutic source for chronic degenerative diseases including osteoporosis. MSCs acquire immune regulatory function under the inflammatory cytokines. Since interleukin (IL) 1¥â is known to be one of inflammatory cytokines involved in osteoporosis progression, treatment of IL1¥â with TMSCs may enhance immunomodulatory function and therapeutic effects of TMSCs in osteoporosis.
Methods: For IL1¥â priming, TMSCs were cultured in the presence of the medium containing IL1¥â for 1 day. Characteristics of IL1¥â priming TMSCs such as multipotent differentiation properties, anti-inflammatory potential, and suppression of osteoclast differentiation were assessed in vitro. For in vivo efficacy study, IL1¥â priming TMSCs were intravenously infused twice with ovariectomized (OVX) osteoporosis mouse model, and blood serum and bone parameters from micro computed tomography images were analyzed.
Results: IL1¥â priming TMSCs had an enhanced osteogenic differentiation and secreted factors that regulate both osteoclastogenesis and osteoblastogenesis. IL1¥â priming TMSCs also suppressed proliferation of peripheral blood mononuclear cells (PBMCs) and decreased expression of Receptor activator of nuclear factor kappa-¥Â ligand (RANKL) in PHA-stimulated PBMCs. Furthermore, osteoclast specific genes such as Nuclear factor of activated T cells c1 (NFATc1) were effectively down regulated when co-cultured with IL1¥â priming TMSCs in RANKL induced osteoclasts. In OVX mice, IL1¥â priming TMSCs induced low level of serum RANKL/osteoprotegerin (OPG) ratio on the first day of the last administration. Four weeks after the last administration, bone mineral density and serum Gla-osteocalcin were increased in IL1¥â priming TMSC-treated OVX mice. Furthermore, bone formation and bone resorption markers that had been decreased in OVX mice with low calcium diet were recovered by infusion of IL1¥â priming TMSCs.
Conclusion: IL1¥â priming can endow constant therapeutic efficacy with TMSCs, which may contribute to improve bone density and maintain bone homeostasis in postmenopausal osteoporosis. Therefore, IL1¥â priming TMSCs can be a new therapeutic option for treating postmenopausal osteoporosis.
|
|
KEYWORD
|
|
Palatine tonsil, Mesenchymal stem cells, Interleukin 1¥â, Osteoporosis
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|