Mesenchymal stem cells plus bone repair materials as a therapeutic strategy for abnormal bone metabolism: Evidence of clinical efficacy and mechanisms of action implied

2021 ◽  
Vol 172 ◽  
pp. 105851
Author(s):  
Shuqin Zhang ◽  
Denghui Xie ◽  
Qun Zhang
2019 ◽  
Vol 70 (6) ◽  
pp. 1983-1987
Author(s):  
Cristian Trambitas ◽  
Anca Maria Pop ◽  
Alina Dia Trambitas Miron ◽  
Dorin Constantin Dorobantu ◽  
Flaviu Tabaran ◽  
...  

Large bone defects are a medical concern as these are often unable to heal spontaneously, based on the host bone repair mechanisms. In their treatment, bone tissue engineering techniques represent a promising approach by providing a guide for osseous regeneration. As bioactive glasses proved to have osteoconductive and osteoinductive properties, the aim of our study was to evaluate by histologic examination, the differences in the healing of critical-sized calvarial bone defects filled with bioactive glass combined with adipose-derived mesenchymal stem cells, compared to negative controls. We used 16 male Wistar rats subjected to a specific protocol based on which 2 calvarial bone defects were created in each animal, one was filled with Bon Alive S53P4 bioactive glass and adipose-derived stem cells and the other one was considered control. At intervals of one week during the following month, the animals were euthanized and the specimens from bone defects were histologically examined and compared. The results showed that this biomaterial was biocompatible and the first signs of osseous healing appeared in the third week. Bone Alive S53P4 bioactive glass could be an excellent bone substitute, reducing the need of bone grafts.


Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 339
Author(s):  
Tobias Grossner ◽  
Uwe Haberkorn ◽  
Tobias Gotterbarm

First-line analgetic medication used in the field of musculoskeletal degenerative diseases, like Nonsteroidal anti-inflammatory drugs (NSAIDs), reduces pain and prostaglandin synthesis, whereby peptic ulcers are a severe adverse effect. Therefore, proton pump inhibitors (PPI) are frequently used as a concomitant medication to reduce this risk. However, the impact of NSAIDs or metamizole, in combination with PPIs, on bone metabolism is still unclear. Therefore, human mesenchymal stem cells (hMSCs) were cultured in monolayer cultures in 10 different groups for 21 days. New bone formation was induced as follows: Group 1 negative control group, group 2 osteogenic differentiation media (OSM), group 3 OSM with pantoprazole (PAN), group 4 OSM with ibuprofen (IBU), group 5 OSM with diclofenac (DIC), group 6 OSM with metamizole (MET), group 7 OSM with ibuprofen and pantoprazole (IBU + PAN), group 8 OSM with diclofenac and pantoprazole (DIC + PAN), group 9 OSM with metamizole and pantoprazole (MET + PAN) and group 10 OSM with diclofenac, metamizole and pantoprazole (DIC + MET + PAN). Hydroxyapatite content was evaluated using high-sensitive radioactive 99mTc-HDP labeling. Within this study, no evidence was found that the common analgetic medication, using NSAIDs alone or in combination with pantoprazole and/or metamizole, has any negative impact on the osteogenic differentiation of mesenchymal stem cells in vitro. To the contrary, the statistical results indicate that pantoprazole alone (group 3 (PAN) (p = 0.016)) or diclofenac alone (group 5 (DIC) (p = 0.008)) enhances the deposition of minerals by hMSCS in vitro. There is an ongoing discussion between clinicians in the field of orthopaedics and traumatology as to whether post-surgical (pain) medication has a negative impact on bone healing. This is the first hMSC in vitro study that investigates the effects of pain medication in combination with PPIs on bone metabolism. Our in vitro data indicates that the assumed negative impact on bone metabolism is subsidiary. These findings substantiate the thesis that, in clinical medicine, the patient can receive every pain medication needed, whether or not in combination with PPIs, without any negative effects for the osteo-regenerative potential.


2021 ◽  
Vol 22 (13) ◽  
pp. 7058
Author(s):  
Thorsten Kirsch ◽  
Fenglin Zhang ◽  
Olivia Braender-Carr ◽  
Mary K. Cowman

Mesenchymal stem cells (MSCs) obtained from various sources, including bone marrow, have been proposed as a therapeutic strategy for the improvement of tissue repair/regeneration, including the repair of cartilage defects or lesions. Often the highly inflammatory environment after injury or during diseases, however, greatly diminishes the therapeutic and reparative effectiveness of MSCs. Therefore, the identification of novel factors that can protect MSCs against an inflammatory environment may enhance the effectiveness of these cells in repairing tissues, such as articular cartilage. In this study, we investigated whether a peptide (P15-1) that binds to hyaluronan (HA), a major component of the extracellular matrix of cartilage, protects bone-marrow-derived MSCs (BMSCs) in an inflammatory environment. The results showed that P15-1 reduced the mRNA levels of catabolic and inflammatory markers in interleukin-1beta (IL-1β)-treated human BMSCs. In addition, P15-1 enhanced the attachment of BMSCs to HA-coated tissue culture dishes and stimulated the chondrogenic differentiation of the multipotential murine C3H/10T1/2 MSC line in a micromass culture. In conclusion, our findings suggest that P15-1 may increase the capacity of BMSCs to repair cartilage via the protection of these cells in an inflammatory environment and the stimulation of their attachment to an HA-containing matrix and chondrogenic differentiation.


2005 ◽  
Vol 1049 (1) ◽  
pp. 97-106 ◽  
Author(s):  
CARL A. GREGORY ◽  
WILLIAM G. GUNN ◽  
EMIGDIO REYES ◽  
ANGELA J. SMOLARZ ◽  
JAMES MUNOZ ◽  
...  

Author(s):  
Shasha Zou ◽  
Tingting Chen ◽  
Yanan Wang ◽  
Ruhui Tian ◽  
Lingling Zhang ◽  
...  

2011 ◽  
Vol 16 (5) ◽  
pp. 606-612 ◽  
Author(s):  
Dae Gyu Park ◽  
Kyung Gon Kim ◽  
Tae-Jin Lee ◽  
Joo-Young Kim ◽  
Eon Gi Sung ◽  
...  

2019 ◽  
Vol 107 (7) ◽  
pp. 1491-1512 ◽  
Author(s):  
Jie Liao ◽  
Shuai Wu ◽  
Kun Li ◽  
Yubo Fan ◽  
Nicholas Dunne ◽  
...  

2020 ◽  
Vol 28 (1) ◽  
pp. 283-302
Author(s):  
Dandan Zhang ◽  
Ni Ni ◽  
Yuyao Wang ◽  
Zhimin Tang ◽  
Huiqin Gao ◽  
...  

AbstractAdipose-derived mesenchymal stem cells (ADSCs) are promising candidate for regenerative medicine to repair non-healing bone defects due to their high and easy availability. However, the limited osteogenic differentiation potential greatly hinders the clinical application of ADSCs in bone repair. Accumulating evidences demonstrate that circular RNAs (circRNAs) are involved in stem/progenitor cell fate determination, but their specific role in stem/progenitor cell osteogenesis, remains mostly undescribed. Here, we show that circRNA-vgll3 originating from the vgll3 locus markedly enhances osteogenic differentiation of ADSCs; nevertheless, silencing of circRNA-vgll3 dramatically attenuates ADSC osteogenesis. Furthermore, we validate that circRNA-vgll3 functions in ADSC osteogenesis through a circRNA-vgll3/miR-326-5p/integrin α5 (Itga5) pathway. Itga5 promotes ADSC osteogenic differentiation and miR-326-5p suppresses Itga5 translation. CircRNA-vgll3 directly sequesters miR-326-5p in the cytoplasm and inhibits its activity to promote osteogenic differentiation. Moreover, the therapeutic potential of circRNA-vgll3-modified ADSCs with calcium phosphate cement (CPC) scaffolds was systematically evaluated in a critical-sized defect model in rats. Our results demonstrate that circRNA-vgll3 markedly enhances new bone formation with upregulated bone mineral density, bone volume/tissue volume, trabeculae number, and increased new bone generation. This study reveals the important role of circRNA-vgll3 during new bone biogenesis. Thus, circRNA-vgll3 engineered ADSCs may be effective potential therapeutic targets for bone regenerative medicine.


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