Evaluation of Intravenously Delivered Allogeneic Mesenchymal Stem Cells for Treatment of Elbow Osteoarthritis in Dogs: A Pilot Study

2019 ◽  
Vol 32 (03) ◽  
pp. 173-181 ◽  
Author(s):  
Anastasia Olsen ◽  
Valerie Johnson ◽  
Tracy Webb ◽  
Kelly Santangelo ◽  
Steven Dow ◽  
...  

Objectives The aim of this study was to evaluate the safety and collect pilot data measuring clinical effects of intravenously administered, adipose-derived, culture-expanded, allogeneic mesenchymal stem cells in dogs with elbow osteoarthritis. Materials and Methods Dogs (n = 13) with naturally occurring elbow osteoarthritis received three intravenous doses of allogeneic canine mesenchymal stem cells via an open-label clinical trial. Primary outcome measures collected over a 6-month study period included objective gait analysis, accelerometry, owner questionnaires and joint fluid analysis. Results No acute adverse events were observed following repeated intravenous treatment with allogeneic mesenchymal stem cells. A significant improvement in mean client-specific outcome measure (CSOM) activity score and CSOM behaviour score was observed when pre-treatment values were compared with post-treatment values (day >28). In contrast, mean peak vertical force significantly decreased from baseline to post-treatment (>day 28). Weekly activity counts did not show a significant difference between baseline to post-treatment time points. Synovial fluid biomarkers did not change during treatment, and labelled mesenchymal stem cells were rarely detected in synovial fluid samples collected after mesenchymal stem cell administration. Clinical Significance For dogs with naturally occurring elbow osteoarthritis, intravenous administration of mesenchymal stem cells was clinically well tolerated. While some subjective outcome measures showed significant improvements, objective outcome measures did not confirm similar changes. Further research is needed before intravenous mesenchymal stem cells can be recommended as a treatment for elbow osteoarthritis in dogs.

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Haritz Gurruchaga ◽  
Laura Saenz del Burgo ◽  
Ane Garate ◽  
Diego Delgado ◽  
Pello Sanchez ◽  
...  

2017 ◽  
Vol 487 (2) ◽  
pp. 457-463 ◽  
Author(s):  
Farong Ou ◽  
Kai Su ◽  
Jiadong Sun ◽  
Wenting Liao ◽  
Yu Yao ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Zayed ◽  
Steven Newby ◽  
Nabil Misk ◽  
Robert Donnell ◽  
Madhu Dhar

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Fang Li ◽  
Jianglin Chen ◽  
Mengjia Gong ◽  
Yang Bi ◽  
Chengchen Hu ◽  
...  

Mesenchymal stem cells (MSCs) are multipotent progenitor cells in adult tissues. The aim of this study is to isolate and identify synovial fluid-derived mesenchymal stromal cells (SF-MSCs) from the popliteal cyst fluid of pediatric patients. SF-MSCs were collected from the popliteal cyst fluid of pediatric patients during cystectomy surgery. After cyst fluid extraction and adherent culturing, in vitro morphology, growth curve, and cell cycle were observed. The expression of stem cell surface markers was analyzed by flow cytometry, and expression of cell marker protein was detected by immunofluorescence. SF-MSCs were cultured in osteogenic, adipogenic, and chondrogenic differentiation medium. The differentiation potential of SF-MSCs was analyzed by alkaline phosphatase (Alizarin Red), Oil Red O, and Alcian blue. Antibody detection of human angiogenesis-related proteins was performed compared with bone marrow mesenchymal stem cells (BM-MSCs). The results show that SF-MSCs from the popliteal cyst fluid of pediatric patients showed a shuttle appearance and logarithmic growth. Flow cytometry analysis revealed that SF-MSCs were negative for hematopoietic lineage markers (CD34, CD45) and positive for MSC markers (CD44, CD73, CD90, and CD105). Interstitial cell marker (vimentin) and myofibroblast-like cell marker alpha-smooth muscle actin (α-SMA) were positive. These cells could differentiate into osteogenic, adipogenic, and chondrogenic lineages, respectively. Several types of human angiogenesis-related proteins were detected in the cell secretory fluid. These results show that we successfully obtained SF-MSCs from the popliteal cyst fluid of pediatric patients, which have the potential to be a valuable source of MSCs.


2019 ◽  
Vol 28 (12) ◽  
pp. 1490-1506 ◽  
Author(s):  
Yu You ◽  
Di-guang Wen ◽  
Jian-ping Gong ◽  
Zuo-jin Liu

Liver transplantation has been deemed the best choice for end-stage liver disease patients but immune rejection after surgery is still a serious problem. Patients have to take immunosuppressive drugs for a long time after liver transplantation, and this often leads to many side effects. Mesenchymal stem cells (MSCs) gradually became of interest to researchers because of their powerful immunomodulatory effects. In the past, a large number of in vitro and in vivo studies have demonstrated the great potential of MSCs for participation in posttransplant immunomodulation. In addition, MSCs also have properties that may potentially benefit patients undergoing liver transplantation. This article aims to provide an overview of the current understanding of the immunomodulation achieved by the application of MSCs in liver transplantation, to discuss the problems that may be encountered when using MSCs in clinical practice, and to describe some of the underlying capabilities of MSCs in liver transplantation. Cell–cell contact, soluble molecules, and exosomes have been suggested to be critical approaches to MSCs’ immunoregulation in vitro; however, the exact mechanism, especially in vivo, is still unclear. In recent years, the clinical safety of MSCs has been proven by a series of clinical trials. The obstacles to the clinical application of MSCs are decreasing, but large sample clinical trials involving MSCs are still needed to further study their clinical effects.


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