scholarly journals Cryopreserved clumps of mesenchymal stem cell/extracellular matrix complexes retain osteogenic capacity and induce bone regeneration

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Souta Motoike ◽  
Mikihito Kajiya ◽  
Nao Komatsu ◽  
Manabu Takewaki ◽  
Susumu Horikoshi ◽  
...  
2019 ◽  
Vol 20 (16) ◽  
pp. 3970 ◽  
Author(s):  
Souta Motoike ◽  
Mikihito Kajiya ◽  
Nao Komatsu ◽  
Susumu Horikoshi ◽  
Tomoya Ogawa ◽  
...  

Three-dimensional clumps of mesenchymal stem cell (MSC)/extracellular matrix (ECM) complexes (C-MSCs) consist of cells and self-produced ECM. We demonstrated previously that C-MSCs can be transplanted into bone defect regions with no artificial scaffold to induce bone regeneration. To apply C-MSCs in a clinical setting as a reliable bone regenerative therapy, the present study aimed to generate C-MSCs in xeno-free/serum-free conditions that can exert successful bone regenerative properties and to monitor interactions between grafted cells and host cells during bone healing processes. Human bone marrow-derived MSCs were cultured in xeno-free/serum-free medium. To obtain C-MSCs, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. Then, C-MSCs were transplanted into an immunodeficient mouse calvarial defect model. Transplantation of C-MSCs induced bone regeneration in a time-dependent manner. Immunofluorescence staining showed that both donor human cells and host mice cells contributed to bone reconstruction. Decellularized C-MSCs implantation failed to induce bone regeneration, even though the host mice cells can infiltrate into the defect area. These findings suggested that C-MSCs generated in xeno-free/serum-free conditions can induce bone regeneration via direct and indirect osteogenesis.


2020 ◽  
Vol 11 ◽  
pp. 204173142092691 ◽  
Author(s):  
Rui Dong ◽  
Yun Bai ◽  
Jingjin Dai ◽  
Moyuan Deng ◽  
Chunrong Zhao ◽  
...  

Recently, extracellular matrix-based tissue-engineered bone is a promising approach to repairing bone defects, and the seed cells are mostly mesenchymal stem cells. However, bone remodelling is a complex biological process, in which osteoclasts perform bone resorption and osteoblasts dominate bone formation. The interaction and coupling of these two kinds of cells is the key to bone repair. Therefore, the extracellular matrix secreted by the mesenchymal stem cells alone cannot mimic a complex bone regeneration microenvironment, and the addition of extracellular matrix by preosteoclasts may contribute as an effective strategy for bone regeneration. Here, we established the mesenchymal stem cell/preosteoclast extracellular matrix -based tissue-engineered bones and demonstrated that engineered-scaffolds based on mesenchymal stem cell/ preosteoclast extracellular matrix significantly enhanced osteogenesis in a 3 mm rat femur defect model compared with mesenchymal stem cell alone. The bioactive proteins released from the mesenchymal stem cell/ preosteoclast extracellular matrix based tissue-engineered bones also promoted the migration, adhesion, and osteogenic differentiation of mesenchymal stem cells in vitro. As for the mechanisms, the iTRAQ-labeled mass spectrometry was performed, and 608 differentially expressed proteins were found, including the IGFBP5 and CXCL12. Through in vitro studies, we proved that CXCL12 and IGFBP5 proteins, mainly released from the preosteoclasts, contributed to mesenchymal stem cells migration and osteogenic differentiation, respectively. Overall, our research, for the first time, introduce pre-osteoclast into the tissue engineering of bone and optimize the strategy of constructing extracellular matrix–based tissue-engineered bone using different cells to simulate the natural bone regeneration environment, which provides new sight for bone tissue engineering.


2019 ◽  
Vol 7 (6) ◽  
pp. 2452-2467 ◽  
Author(s):  
Shijie Liu ◽  
Yiyun Wang ◽  
Jian Wang ◽  
Pengcheng Qiu ◽  
Shengyu Wang ◽  
...  

Bone regenerative therapies have been explored using various biomaterial systems.


2016 ◽  
Vol 23 (12) ◽  
pp. 1941-1951 ◽  
Author(s):  
Jiajia Xu ◽  
Yiyun Wang ◽  
Jing Li ◽  
Xudong Zhang ◽  
Yiyun Geng ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153412 ◽  
Author(s):  
Chia Wei Chang ◽  
Tye Petrie ◽  
Alycia Clark ◽  
Xin Lin ◽  
Claus S. Sondergaard ◽  
...  

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