scholarly journals Wnt/β-Catenin Pathway Balances Scaffold Degradation and Bone Formation in Tissue-Engineered Laminae

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Hailong Li ◽  
Linli Li ◽  
Yiqun He ◽  
Wei Mao ◽  
Haofei Ni ◽  
...  

Tissue engineering provides a promising way for the regeneration of artificial vertebral laminae. Previous studies have confirmed the feasibility of reconstructing vertebral laminae via hydroxyapatite-collagen I scaffolds and mesenchymal stromal cells. However, there were no studies exploring the degradation of hydroxyapatite-collagen I scaffolds and the function of Wnt/β-catenin pathway in the process. In this study, tissue-engineered laminae (TEL) were constructed by nanohydroxyapatite/collagen I scaffolds and umbilical cord Wharton’s Jelly mesenchymal stromal cells (WJ-MSCs). Cell attachment was observed by scanning electron microscopy, and cell viability was confirmed by Live/Dead staining. The rat models were randomly divided into control and β-catenin inhibition groups. Vertebral lamina defect rat models were made on the fifth lumbar vertebrate, and TEL was implanted into the defect site. After 14 weeks, the newborn laminae were harvested for microcomputed tomography, histology, or transcriptional profile analysis. We found that, for the control group, the newborn lamina formation matched with the scaffold degradation and complete newborn laminae formed at the 14th week; for the β-catenin inhibition group, the scaffold degradation rate overrated the lamina formation and no complete artificial laminae were formed at the 14th week. In addition, the osteoclastic genes, such as Cathepsin K or RANKL, in the control groups were significantly lower than the β-catenin inhibition group, and the antiosteoclastic gene, OPG, in the control group was significantly higher than the β-catenin inhibition group. In conclusion, inhibition of Wnt/β-catenin pathway led to speedy scaffold degradation and deferred artificial lamina formation. Wnt/β-catenin pathway played a critical role in maintaining the balance between scaffold degradation and bone formation in the process of vertebral lamina reconstruction.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yiqin Zhou ◽  
Haobo Li ◽  
Dong Xiang ◽  
Jiahua Shao ◽  
Qiwei Fu ◽  
...  

Abstract Introduction To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method. Methods Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention. Results Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups. Conclusions The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions. Trial registration ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901.


2021 ◽  
Vol 66 (4) ◽  
pp. 5-12
Author(s):  
A. Rastorgueva ◽  
T. Astrelina ◽  
V. Brunchukov ◽  
D. Usupzhanova ◽  
I. Kobzeva ◽  
...  

Background: To compare the results of the use of mesenchymal stromal cells (MSCs) of human gingival mucosa and MSCs of rat gingival mucosa, their conditioned media, and to evaluate their effect on tissue regeneration in local radiation injury (LRI). Material and methods: The study included 120 white male Wistar rats weighing 210 ± 30 g at the age of 8–12 weeks, randomized into 6 groups (20 animals each): control (C), animals did not receive therapy; control with the introduction of culture medium concentrate (CM) three times for 1, 14, 21 days; administration of human gingival mucosa MSCs (HM) at a dose of 2 million per 1 kg three times for 1, 14, 21 days; administration of human gingival mucosa MSCS conditioned medium concentrate (HMCM) at a calculated dose of 2 million cells per 1 kg three times for 1, 14, 21 days; administration of rat gingival mucosal MSCs (RM) at a dose of 2 million cells per 1 kg three times for 1, 14, 21 days; administration of rat gingival mucosal MSCS (RMCM) conditioned medium concentrate at a calculated dose of 2 million cells per 1 kg three times for 1, 14, 21 days. Each laboratory animal was observed 17 times: on 1, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91, 98, 105, 112 day after the burn simulation. Histological (hematoxylin-eosin staining) and immunohistochemical (CD31, CD68, VEGF, PGP 9.5, MMP2,9, Collag 1, TIMP 2) studies were performed. LRI was modeled on an X-ray machine at a dose of 110 Gy. MSCs were cultured according to the standard method up to 3–5 passages, the conditioned medium was taken and concentrated 10 times. The immunophenotype of MSCs (CD34, CD45, CD90, CD105, CD73, HLA-DR) and viability (7‑ADD) were determined by flow cytofluorimetry. Results: In a comparative analysis with the control group (C), starting from the 42nd day of the study, a tendency to reduce the area of skin ulcers in animals in all groups was observed, despite the fact that not all days had statistically significant differences. On day 112th, complete healing of skin ulcers in the CM group was observed in 40 % of animals in the HM group – in 60 %, in the HMCM group – in 20 % of animals, in the RMCM group–20 %, and in the C and RM groups there were no animals with a prolonged wound defect. Positive expression of the VEGF marker was observed in groups C and CM on the 28th day and in experimental groups (HM, HMCM, RM, RMCM) on the 112th day. A statistically significant increase in the CD68 marker was observed in groups C, RM, and RMCM, while the remaining groups showed a decrease in the number of macrophages.


2007 ◽  
Vol 361-363 ◽  
pp. 1067-1070 ◽  
Author(s):  
Asako Matsushima ◽  
Noriko Kotobuki ◽  
Mika Tadokoro ◽  
Hajime Ohgushi

Hydroxyapatite (HA) ceramics together with various kinds of osteogenic cells have been used in bone tissue engineering. It is well known that the ceramics structure and composition affect cell proliferation / differentiation. In this study, three different types of HA ceramics were used to investigate initial cell attachment followed by osteoblastic differentiation of human mesenchymal stromal cells (MSCs). The results indicated that micro-pore affected the cell attachment and porosity (pore diameter and inter-pore connection) was the key to allow spacious distribution of the viable cells in the ceramics. This study also confirmed that surface pore areas of HA ceramics support the differentiation of human MSCs and thus the ceramics have the capability to regenerate damaged bone tissue.


Author(s):  
Lingli Zhang ◽  
Yu Yuan ◽  
Wei Wu ◽  
Zhongguang Sun ◽  
Le Lei ◽  
...  

As a type of multipotential cells, bone marrow mesenchymal stromal cells (BMMSCs) can differentiate into chondrocytes, osteoblasts, and adipocytes under different loading condition or specific microenvironment. Previous studies have shown that BMMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. The appropriate physical activity and exercise could help attenuate bone loss, effectively stimulate bone formation, increase bone mineral density (BMD), prevent the progression of osteoporosis, and reduce the risk of bone fractures. Bone morphogenetic protein (BMP) is originally discovered as a protein with heterotopic bone-inducing activity in the bone matrix that exerts a critical role in multiple stages of bone metabolism. In the present study, the medium-intensity treadmill exercise enhanced bone formation and increased osteocalcin (OCN) and osteopontin (OPN) mRNA expression as well as activation of the BMP-Smad signaling pathway in vivo. In order to investigate the effect of a BMP-Smad signaling pathway, we injected mice with activated enzyme inhibitors (LDN-193189HCL) and subjected the mice to treadmill exercise intervention. LDN-193189HCL attenuated the BMD and bone mass mediated by medium-intensity exercise and BMP-Smad signaling pathway.


2018 ◽  
Vol 27 (8) ◽  
pp. 1210-1221 ◽  
Author(s):  
A. Liew ◽  
C. Baustian ◽  
D. Thomas ◽  
E. Vaughan ◽  
C. Sanz-Nogués ◽  
...  

Intramuscular administration of mesenchymal stromal cells (MSCs) represents a therapeutic option for diabetic critical limb ischemia. Autologous or allogeneic approaches may be used but disease-induced cell dysfunction may limit therapeutic efficacy in the former. Our aim was to compare the efficacy of allogeneic and autologous MSC transplantation in a model of hindlimb ischemia in diabetes mellitus and to determine whether allogeneic transplantation would result in the activation of an immune response. MSCs were isolated from C57BL/6 (B6) and diabetic obese C57BKSdb/db mice. Phosphate-buffered saline (control group), and MSCs (1 × 106) from B6 (allogeneic group) or C57BKSdb/db (syngeneic group) were administered intramuscularly into the ischemic thigh of C57BKSdb/db mice following the induction of hindlimb ischemia. MSCs derived from both mouse strains secrete several angiogenic factors, suggesting that the potential therapeutic effect is due to paracrine signaling. Administration of allogeneic MSCs significantly improved blood perfusion as compared with the control group on week 2 and 3, post-operatively. In comparison with the control group, syngeneic MSCs significantly improved blood perfusion at week 2 only. There was no statistical difference in blood perfusion between allogeneic and syngeneic MSC groups at any stages. There was no statistical difference in ambulatory and necrosis score among the three groups. Amputation of toes was only observed in the control group (one out of seven animals). Alloantibody was detected in three out of the eight mice that received allogeneic MSCs but was not observed in the other groups. In summary, we demonstrated comparable efficacy after transplantation of autologous and allogeneic MSCs in a diabetic animal model despite generation of an immune response.


2015 ◽  
Vol 13 ◽  
pp. 254-265 ◽  
Author(s):  
Wanxun Yang ◽  
Sanne K. Both ◽  
Gerjo J.V.M. van Osch ◽  
Yining Wang ◽  
John A. Jansen ◽  
...  

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