Osteogenic Potency of Secretome Bone Marrow Derived Mesenchymal Stem Cells: A Literature Review

2018 ◽  
Vol 24 (8) ◽  
pp. 6206-6208
Author(s):  
Ismail Hadisoebroto Dilogo ◽  
Jessica Fiolin ◽  
Petrus Aprianto

Treatment of non-union bone healing has been an unsolved problem in Orthopaedic surgery despite many advances. The most commonly adapted concept is the diamond concept including the osteoprogenitor cells, osteoinductive proteins, osteoconductive scaffolds and mechanical stability. Recent study groups worldwide have been studying the Mesenchymal Stem Cells as an adjunct to increase the bone healing process. However, newer literatures have shown that only few number of MSC transplanted will integrate. This paracrine mechanism is mediated by active secretion of cytokines, growth factors and enzymes called the secretome which is produced as a byproduct during the process of MSC culture. The addition of secretome itself alone is predicted to have the similar effect as the transplantation of MSC with less cost needed, and easier to obtain. The effect of MSC secretome has shown positive result on neurodegenerative disease, acute kidney disease, and cancer; but the effect on bone regeneration itself has never been studied. The MSC secretome have been proven to contain various cytokines (TGβ, some interleukins, GCSF, and many other cytokines) and growth factors (VEGF, EGF, PDGF, IGF-1, IGF-II, PLGF, HGF, NGF, BDNF). We also suspect the osteoinductive profile of MSC secretome due to the existence of BMP-2 which can be analysed using the ELISA spectrophotometry. The osteoinductive profile of secretome MSC will be able to replace the need of recombinant human BMP-2 (rhBMP-2) transplantation in treating bone defect and diminish the risk of excessive inflammation created by BMP-2 and also the carcinogenic potency.

2019 ◽  
Vol 10 ◽  
pp. 204173141982779
Author(s):  
Kelly Campbell ◽  
Shailesh Naire ◽  
Jan Herman Kuiper

Autologous chondrocyte implantation is a cell-based therapy for treating chondral defects. The procedure begins by inserting chondrocytes into the defect region. The chondrocytes initiate healing by proliferating and depositing extracellular matrix, which allows them to migrate into the defect until it is completely filled with new cartilage. Mesenchymal stem cells can be used instead of chondrocytes with similar long-term results. The main differences are at early times since mesenchymal stem cells must first differentiate into chondrocytes before cartilage is formed. To better understand this repair process, we present a mathematical model of cartilage regeneration after cell therapy. We extend our previous work to include the cell–cell interaction between mesenchymal stem cells and chondrocytes via growth factors. Our results show that matrix formation is enhanced at early times in the presence of growth factors. This study reinforces the importance of mesenchymal stem cell and chondrocyte interaction in the cartilage healing process as hypothesised in experimental studies.


Author(s):  
Fatemeh Hejazi ◽  
Vahid Ebrahimi ◽  
Mehrdad Asgary ◽  
Abbas Piryaei ◽  
Mohammad Javad Fridoni ◽  
...  

AbstractOsteoporosis is a common bone disease that results in elevated risk of fracture, and delayed bone healing and impaired bone regeneration are implicated by this disease. In this study, Elastin/Polycaprolactone/nHA nanofibrous scaffold in combination with mesenchymal stem cells were used to regenerate bone defects. Cytotoxicity, cytocompatibility and cellular morphology were evaluated in vitro and observations revealed that an appropriate environment for cellular attachment, growth, migration, and proliferation is provided by this scaffold. At 3 months following ovariectomy (OVX), the rats were used as animal models with an induced critical size defect in the femur to evaluate the therapeutic potential of osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) seeded on 3 dimension (3D) scaffolds. In this experimental study, 24 female Wistar rats were equally divided into three groups: Control, scaffold (non-seeded BM-MSC), and scaffold + cell (seeded BM-MSC) groups. 30 days after surgery, the right femur was removed, and underwent a stereological analysis and RNA extraction in order to examine the expression of Bmp-2 and Vegf genes. The results showed a significant increase in stereological parameters and expression of Bmp-2 and Vegf in scaffold and scaffold + cell groups compared to the control rats. The present study suggests that the use of the 3D Elastin/Polycaprolactone (PCL)/Nano hydroxyapatite (nHA) scaffold in combination with MSCs may improve the fracture regeneration and accelerates bone healing at the osteotomy site in rats.


Stem Cells ◽  
2009 ◽  
pp. N/A-N/A ◽  
Author(s):  
Xiaohong Wang ◽  
Tiemin Zhao ◽  
Wei Huang ◽  
Tao Wang ◽  
Jiang Qian ◽  
...  

2016 ◽  
Vol 695 ◽  
pp. 118-122 ◽  
Author(s):  
Razvan Ene ◽  
Zsombor Panti ◽  
Mihai Nica ◽  
Marian Pleniceanu ◽  
Patricia Ene ◽  
...  

Distal comminuted tibial fracture with or without intra-articular involvement is a very common injury of the lower limb, especially in younger patients due to high energy trauma. The anatomical and biomechanical properties of this segment of tibia, makes this pathology a major surgical challenge with a preserved clinical outcome. The aim of this study is to present different outcome of tibial fracture, treated with open reduction and internal fixation (ORIF) with titanium angle locking plates (ALP) and to underline the physiological and non-physiological bone healing effects on implants. In this study we included 48 patients with tibial pilon fracture who underwent to ORIF, applying ALP in the Orthopedics and Trauma department of the University Emergency Hospital in Bucharest. Due to preserved biomechanical properties of ALP and this anatomical region, weight bearing is not allowed till 6 to 8 weeks. Comminuted fracture of this part of tibia often have de-vascularized bony fragments which leads to delayed union or non-union. These complications often lead to implant failure, improper bone healing or non-union. Internal fixation with angle stable screws, offers a good stability of reduction in the early postoperative period. Titanium angle locking plates offers good anatomical reduction and stable fixation in the early period of healing process. Due to its rigid, fixed position of the screws in the plates, bone remodelling during healing process and early weight bearing, increases the mechanical failure of implant.Keywords: tibial pilon fractures, angle locking plates, implant failure.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Markus Huber-Lang ◽  
Rebecca Wiegner ◽  
Lorenz Lampl ◽  
Rolf E. Brenner

Mesenchymal stem cells (MSCs) are multipotent cells that are considered indispensable in regeneration processes after tissue trauma. MSCs are recruited to damaged areas via several chemoattractant pathways where they function as “actors” in the healing process by the secretion of manifold pro- and anti-inflammatory, antimicrobial, pro- and anticoagulatory, and trophic/angiogenic factors, but also by proliferation and differentiation into the required cells. On the other hand, MSCs represent “targets” during the pathophysiological conditions after severe trauma, when excessively generated inflammatory mediators, complement activation factors, and damage- and pathogen-associated molecular patterns challenge MSCs and alter their functionality. This in turn leads to complement opsonization, lysis, clearance by macrophages, and reduced migratory and regenerative abilities which culminate in impaired tissue repair. We summarize relevant cellular and signaling mechanisms and provide an up-to-date overview about promising future therapeutic MSC strategies in the context of severe tissue trauma.


Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1408
Author(s):  
Susumu Horikoshi ◽  
Mikihito Kajiya ◽  
Souta Motoike ◽  
Mai Yoshino ◽  
Shin Morimoto ◽  
...  

Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be transplanted into tissue defect site with no artificial scaffold. Importantly, most bone formation in the developing process or fracture healing proceeds via endochondral ossification. Accordingly, this present study investigated whether C-MSCs generated with chondro-inductive medium (CIM) can induce successful bone regeneration and assessed its healing process. Human bone marrow-derived MSCs were cultured with xeno-free/serum-free (XF) growth 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. The cell clumps, i.e., C-MSCs, were maintained in XF-CIM. C-MSCs generated with XF-CIM showed enlarged round cells, cartilage matrix, and hypertrophic chondrocytes genes elevation in vitro. Transplantation of C-MSCs generated with XF-CIM induced successful bone regeneration in the SCID mouse calvaria defect model. Immunofluorescence staining for human-specific vimentin demonstrated that donor human and host mouse cells cooperatively contributed the bone formation. Besides, the replacement of the cartilage matrix into bone was observed in the early period. These findings suggested that cartilaginous C-MSCs generated with XF-CIM can induce bone regeneration via endochondral ossification.


2016 ◽  
Vol 38 (1) ◽  
pp. 319-329 ◽  
Author(s):  
Yulei Gao ◽  
Yinquan Zhang ◽  
Yanghu Lu ◽  
Yi Wang ◽  
Xingrui Kou ◽  
...  

Background/Aims: This study investigated the effect of silencing TOB1 (Transducer of ERBB2, 1) expression in bone marrow-derived mesenchymal stem cells (MSCs) on MSC-facilitated tendon-bone healing in a rat supraspinatus repair model. Methods: Rat MSCs were transduced with a recombinant lentivirus encoding short hairpin RNA (shRNA) against TOB1. MSC cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The effect of MSCs with TOB1 deficiency on tendon-bone healing in a rat rotator cuff repair model was evaluated by biomechanical testing, histological analysis and collagen type I and II gene expression. An upstream regulator (miR-218) of TOB1 was determined in MSCs. Results: We found that knockdown of TOB1 significantly increased the proliferative activity of rat MSCs in vitro. When MSCs with TOB1 deficiency were injected into injured rat supraspinatus tendon-bone junctions, the effect on tendon-bone healing was enhanced compared to treatment with control MSCs with normal TOB1 expression, as evidenced by elevated levels of ultimate load to failure and stiffness, increased amount of fibrocartilage and augmented expression of collagen type I and type II genes. In addition, we found that the TOB1 3′ untranslated region is a direct target of miR-218. Similar to the effect of TOB1 deficiency, overexpression of miR-218 effectively promoted tendon-bone healing in rat. Conclusion: These results suggest that TOB1 may play a negative role in the effect of MSCs on tendon-bone healing, and imply that expression of TOB1 may be regulated by miR-218.


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