Injectable Hydrogel Mediated Delivery of Gene-Engineered Adipose-Derived Stem Cells for Enhanced Osteoarthritis Treatment

2021 ◽  
Author(s):  
Wei Yu ◽  
Bin Hu ◽  
Kofi Oti Boakye-Yiadom ◽  
William Ho ◽  
Qijing Chen ◽  
...  

Osteoarthritis (OA), a chronic and degenerative joint disease, remains a challenge in treatment due to the lack of disease-modifying therapies. As a promising therapeutic agent, adipose-derived stem cells (ADSCs) perform...

2014 ◽  
Vol 9 (6) ◽  
pp. 497-503 ◽  
Author(s):  
Sarah Broeckx ◽  
Marc Suls ◽  
Charlotte Beerts ◽  
Aurelie Vandenberghe ◽  
Bert Seys ◽  
...  

2014 ◽  
Vol 5 ◽  
pp. BTRI.S14578 ◽  
Author(s):  
Girolamo A. Ortolano ◽  
Barry Wenz

Osteoarthritis (OA) is the most prevalent musculoskeletal disease in humans and domestic animals. It causes significant clinical problems and substantial health care costs. In the absence of disease-modifying medical intervention, therapy is currently restricted to palliative measures prior to surgical intervention. We review the pathogenesis, as well as conservative and emerging restorative therapeutic approaches, including cytokines, stem cells, and platelets. The various methods of platelet concentrate preparations and their reported outcomes are discussed. Data collected from the use of intra-articular platelet therapy (IAPT) in dogs are reviewed, which suggest that this approach may delay or in some cases even obviate the need for surgical intervention.


Author(s):  
Gabriella Varcoe ◽  
Julia Tomlinson ◽  
Jane Manfredi

ABSTRACT Polysulfated glycosaminoglycan (PSGAG) is a slow-acting disease-modifying agent used to treat degenerative joint disease. Although labeled for intramuscular use, it is commonly given by owners via a subcutaneous (SC) route. There is little information on adverse events related to SC administration or what other therapies are used concurrently with PSGAG. We hypothesized that SC PSGAG is perceived by owners as having minimal adverse events and that it would most often be given with other therapies. Owners (n = 378) were surveyed about their perceptions regarding SC PSGAG prescribed to dogs at one veterinary rehabilitation clinic. Complete surveys were provided for 69 dogs (two owners had multiple dogs). Overall, 13/69 (18.8%) dogs had an adverse event reported during the use of PSGAG. Most events were considered minor (stomach upset, loose stool, pain at injection site, fear) and did not lead to discontinuation of PSGAG. One dog experienced a moderate adverse event (persistent gastrointestinal symptoms) and one a severe adverse event (thrombocytopenia, bruising), which resolved after discontinuing PSGAG. PSGAG is most commonly administered along with other medications and rehabilitation therapies. The present study demonstrates that SC administration of PSGAG is well tolerated in most of the dogs, with primarily mild, self-resolving adverse events.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stefania Pagani ◽  
Manuela Minguzzi ◽  
Laura Sicuro ◽  
Francesca Veronesi ◽  
Spartaco Santi ◽  
...  

Abstract Osteoarthritis (OA), the most prevalent degenerative joint disease, still lacks a true disease-modifying therapy. The involvement of the NF-κB pathway and its upstream activating kinases in OA pathogenesis has been recognized for many years. The ability of the N-acetyl phenylalanine glucosamine derivative (NAPA) to increase anabolism and reduce catabolism via inhibition of IKKα kinase has been previously observed in vitro and in vivo. The present study aims to confirm the chondroprotective effects of NAPA in an in vitro model of joint OA established with primary cells, respecting both the crosstalk between chondrocytes and synoviocytes and their phenotypes. This model satisfactorily reproduces some features of the previously investigated DMM model, such as the prominent induction of ADAMTS-5 upon inflammatory stimulation. Both gene and protein expression analysis indicated the ability of NAPA to counteract key cartilage catabolic enzymes (ADAMTS-5) and effectors (MCP-1). Molecular analysis showed the ability of NAPA to reduce IKKα nuclear translocation and H3Ser10 phosphorylation, thus inhibiting IKKα transactivation of NF-κB signalling, a pivotal step in the NF-κB-dependent gene expression of some of its targets. In conclusion, our data confirm that NAPA could truly act as a disease-modifying drug in OA.


2021 ◽  
Vol 11 (6) ◽  
pp. 14463-14479

Nano-curcumin (Nano-Cur) is a promising therapeutic agent that has a wide array of effective medicinal potentials. Therefore, the present inquiry aimed to assess Nano-Cur's impact on the therapeutic effect of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in the rat model of liver fibrosis prompted by carbon tetrachloride (CCl4). Liver fibrosis was developed in 30male Wistar albino rats which were divided into five groups, six animals each. The 1st group (CCl4 group) was sacrificed immediately after the induction of liver fibrosis. The 2nd group received a single iv injection of BM-MSCs and left for 4weeks, the3rd group received 100mg/kg b.w. Nano-Cur 3times/week for 4weeks, the 4th group received a single iv injection of 107 BM-MSCs accompanied with Nano-Cur 3times/week for 4weeks, and the 5th group left for 4weeks without any intervention. Data revealed that treatment with BM-MSCs plus Nano-Cur alleviated liver fibrosis through reducing liver oxidative stress and restoring both liver histological picture and enzymatic profile. Additionally, companied treatment resulted in reducing TGFβ1 levels and attenuating the expression of Smad 2,3 and collagen I, III genes. Conversely, most of the pathological lesions were still detected in the recovery group. Nano-Cur improves the therapeutic role of BM-MSCs in liver fibrosis rats.


2021 ◽  
Vol 24 (4) ◽  
pp. 601-607
Author(s):  
K. B Aminkov ◽  
N. H. Mehandzhiyski ◽  
B. Y. Aminkov ◽  
N. Z. Zlateva-Panayotova

Osteoarthritis, also known as degenerative joint disease (DJD), is defined as a progressive and permanent long-term deterioration of the cartilage surrounding the joints. There is no known cause for primary DJD. However, there are a wide variety of causes for secondary DJD, such as trauma, abnormal wear of joints and cartilage, or a congenital defect present at birth such as an improperly formed hip. One of the most popular methods used to biologically enhance healing in the fields of orthopaedic surgery and medicine includes the use of autologous blood products, namely, platelet rich plasma (PRP). Reports suggest that PRP, presumably containing high levels of platelet growth factors, may promote the recovery of the affected cartilage. This case series presents clinical and radiographic findings of three dogs with osteoarthritis of the elbow and knee joints. Pain score were assessed by CBPI (Canine Brief Pain Inventory). Treatment with three-fold intra-articular application of PRP, obtained by double centrifugation method, resulted in significant improvement in the function of the affected joint. Therefore, it could be concluded that PRP was clinically effective in the treatment of osteoarthritis in these three cases.


2020 ◽  
Vol 52 (4) ◽  
pp. 672-681 ◽  
Author(s):  
Jiyun Lee ◽  
Chang Youn Lee ◽  
Jun-Hee Park ◽  
Hyang-Hee Seo ◽  
Sunhye Shin ◽  
...  

Abstract Osteoarthritis (OA) is a common joint disease that results from the disintegration of joint cartilage and the underlying bone. Because cartilage and chondrocytes lack the ability to self-regenerate, efforts have been made to utilize stem cells to treat OA. Although various methods have been used to differentiate stem cells into functional chondrocytes, the currently available methods cannot induce stem cells to undergo differentiation into chondrocyte-like cells without inducing characteristics of hypertrophic chondrocytes, which finally lead to cartilage disintegration and calcification. Therefore, an optimized method to differentiate stem cells into chondrocytes that do not display undesired phenotypes is needed. This study focused on differentiating adipose-derived stem cells (ASCs) into functional chondrocytes using a small molecule that regulated the expression of Sox9 as a key factor in cartilage development and then explored its ability to treat OA. We selected ellipticine (ELPC), which induces chondrocyte differentiation of ASCs, using a GFP-Sox9 promoter vector screening system. An in vivo study was performed to confirm the recovery rate of cartilage regeneration with ASC differentiation into chondrocytes by ELPC in a collagenase-induced animal model of OA. Taken together, these data indicate that ellipticine induces ASCs to differentiate into mature chondrocytes without hypertrophic chondrocytes in vitro and in vivo, thus overcoming a problem encountered in previous studies. These results indicate that ELPC is a novel chondrocyte differentiation-inducing drug that shows potential as a cell therapy for OA.


2021 ◽  
Vol 57 (5) ◽  
pp. 205-211
Author(s):  
Gabriella Varcoe ◽  
Julia Tomlinson ◽  
Jane Manfredi

ABSTRACT Polysulfated glycosaminoglycan (PSGAG) is a slow-acting disease-modifying agent used to treat degenerative joint disease. Although labeled for intramuscular use, it is commonly given by owners via a subcutaneous (SC) route. There is little information on adverse events related to SC administration or what other therapies are used concurrently with PSGAG. We hypothesized that SC PSGAG is perceived by owners as having minimal adverse events and that it would most often be given with other therapies. Owners (n = 378) were surveyed about their perceptions regarding SC PSGAG prescribed to dogs at one veterinary rehabilitation clinic. Complete surveys were provided for 69 dogs (two owners had multiple dogs). Overall, 13/69 (18.8%) dogs had an adverse event reported during the use of PSGAG. Most events were considered minor (stomach upset, loose stool, pain at injection site, fear) and did not lead to discontinuation of PSGAG. One dog experienced a moderate adverse event (persistent gastrointestinal symptoms) and one a severe adverse event (thrombocytopenia, bruising), which resolved after discontinuing PSGAG. PSGAG is most commonly administered along with other medications and rehabilitation therapies. The present study demonstrates that SC administration of PSGAG is well tolerated in most of the dogs, with primarily mild, self-resolving adverse events.


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