Osteoarthritis (OA)

Osteoarthritis (OA) is characterized as a degeneration of cartilage and bone within the joint. Symptoms include joint pain, stiffness, decreased range of motion, and eventually inability/difficulty in performing everyday tasks.

The cause of osteoarthritis is believed to be mechanical stress on a joint and subsequent low grade inflammation. Risk factors for the development of osteoarthritis include previous joint injury, abnormal joint development, and obesity.

Conventional treatment for osteoarthritis includes supportive care (physical therapy, weight loss, and mobility tools), pain medications, and ultimately joint replacement. An artificial joint replacement will typically last 10-15 years.

Stem Cell research on osteoarthritis is focusing on trying to repair and regenerate lost cartilage and bone within the joint. Stem cell treatment for joints and osteoarthritis has by far been the most studied and most successful condition in the regenerative
medicine world.

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The most current research regarding stem cells and OA is given below:

The human umbilical cord stem cells improve the viability of OA degenerated chondrocytes
Hao Wang, Xu Yan, Yuxin Jiang, Zheng Wang, Yufei Li, and Qingdong Shao

Abstract: Osteoarthritis (OA) affects a large number of patients; however, human umbilical cord stem cells exhibit therapeutic potential for treating OA. The aim of the present study was to explore the interaction between human umbilical cord stem cells and degenerated chondrocytes, and the therapeutic potential of human umbilical cord stem cells on degenerated chondrocytes. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were harvested from human umbilical cords, and flow cytometry was used to analyze the surface antigen markers, in addition, chondrogenic, osteogenic and adipogenic differentiation on the cells was investigated. OA cells at P3 were cocultured with hUC-MSCs in a separated co-culture system, and reverse transcription-polymerase chain reaction and western blot were used to evaluate the mRNA, and protein expression of collagen type II (Col2), SRY-box 9 (sox-9) and aggrecan. The level of inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-10, were analyzed by ELISA in the supernatant. hUC-MSCs grow in a fibroblastic shape with stable proliferation. hUC-MSCs expressed cluster of differentiation 44 (CD44), CD73, CD90, CD105; while did not express CD34, CD45, CD106, CD133. After multi-induction, hUC-MSCs were able to differatiate into adipogenic, osteogenic and chondrogenic lineage. hUC-MSCs inhibited the expression of matrix metalloproteinase-13, collagen type X α1 chain and cyclooxygenase-2 in OA chondrocytes, and enhanced the proliferation of OA chondrocytes, while OA chondrocytes stimulated the production of Col2, sox-9 and aggrecan and promoted hUC-MSCs differentiate into chondrocytes. Flow cytometry analysis demonstrated hUC-MSCs have a predominant expression of stem cell markers, while the hematopoietic and endothelial markers were absent. Osteogenic, chondrogenic and adipogenic differentiation was observed in certain induction conditions. hUC-MSCs improved the proliferation of OA chondrocytes and downregulated the expression of inflammatory cytokines, while OA chondrocytes promoted MSCs to differentiate into chondrocytes. Taken together, the co-culture of hUC-MSCs and OA chondrocytes may provide a therapeutic potential in OA treatment.



Cartilage Regeneration in Osteoarthritic Patients by a Composite of Allogeneic Umbilical Cord Blood‐Derived Mesenchymal Stem Cells and Hyaluronate Hydrogel: Results from a Clinical Trial for Safety and Proof‐of‐Concept with 7 Years of Extended Follow‐Up
Yong‐Beom Park, Chul‐Won Ha, Choong‐Hee Lee, Young Cheol Yoon, and Yong‐Geun Park

Abstract: Few methods are available to regenerate articular cartilage defects in patients with osteoarthritis. We aimed to assess the safety and efficacy of articular cartilage regeneration by a novel medicinal product composed of allogeneic human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSCs). Patients with Kellgren‐Lawrence grade 3 osteoarthritis and International Cartilage Repair Society (ICRS) grade 4 cartilage defects were enrolled in this clinical trial. The stem cell‐based medicinal product (a composite of culture‐expanded allogeneic hUCB‐MSCs and hyaluronic acid hydrogel [Cartistem]) was applied to the lesion site. Safety was assessed by the World Health Organization common toxicity criteria. The primary efficacy outcome was ICRS cartilage repair assessed by arthroscopy at 12 weeks. The secondary efficacy outcome was visual analog scale (VAS) score for pain on walking. During a 7‐year extended follow‐up, we evaluated safety, VAS score, International Knee Documentation Committee (IKDC) subjective score, magnetic resonance imaging (MRI) findings, and histological evaluations. Seven participants were enrolled. Maturing repair tissue was observed at the 12‐week arthroscopic evaluation. The VAS and IKDC scores were improved at 24 weeks. The improved clinical outcomes were stable over 7 years of follow‐up. The histological findings at 1 year showed hyaline‐like cartilage. MRI at 3 years showed persistence of the regenerated cartilage. Only five mild to moderate treatment‐emergent adverse events were observed. There were no cases of osteogenesis or tumorigenesis over 7 years. The application of this novel stem cell‐based medicinal product appears to be safe and effective for the regeneration of durable articular cartilage in osteoarthritic knees.


Evaluation of the Curative Effect of Umbilical Cord Mesenchymal Stem Cell Therapy for Knee Arthritis in Dogs Using Imaging Technology
Bei-ying Zhang, Bing-yun Wang, Shao-chuan Li, Dong-zhang Luo, Xiaoshu Zhan, Sheng-feng Chen, Zhi-sheng Chen, Can-ying Liu, Hui-qin Ji, Yin-shan Bai, Dong-sheng Li, and Yang He

Abstract: The aim of this study was to assess the efficacy of canine umbilical cord mesenchymal stem cells (UC-MSCs) on the treatment of knee osteoarthritis in dogs. Methods. Eight dogs were evenly assigned to two groups. The canine model of knee osteoarthritis was established by surgical manipulation of knee articular cartilage on these eight dogs. UC-MSCs were isolated from umbilical cord Wharton’s jelly by 0.1% type collagenase I and identified by immunofluorescence staining and adipogenic and osteogenic differentiation in vitro. A suspension of allogeneic UC-MSCs (1 × 106) and an equal amount of physiological saline was injected into the cavitas articularis in the treated and untreated control groups, respectively, on days 1 and 3 posttreatment. The structure of the canine knee joint was observed by magnetic resonance imaging (MRI), B-mode ultrasonography, and X-ray imaging at the 3rd, 7th, 14th, and 28th days after treatment. Concurrently, the levels of IL-6, IL-7, and TNF-α in the blood of the examined dogs were measured. Moreover, the recovery of cartilage and patella surface in the treated group and untreated group was compared using a scanning electron microscope (SEM) after a 35-day treatment. Results. Results revealed that the isolated cells were UC-MSCs, because they were positive for CD44 and negative for CD34 surface markers, and the cells were differentiated into adipocytes and osteoblasts. Imaging technology showed that as treatment time increased, the high signal in the MRI T2-weighted images decreased, the echo-free space in B ultrasonography images disappeared basically, and the continuous linear hypoechoic region at the trochlear sulcus thickened. On X-ray images, the serrate defect at the ventral cortex of the patella improved, and the low-density gap of the ventral patella and trochlear crest gradually increased in the treated group. On the contrary, the high signal in the MRI T2-weighted images and the echo-free space in B ultrasonography images still increased after a 14-day treatment in the untreated control group, and the linear hypoechoic region was discontinuous. On the X-ray images, there was no improvement in the serrate defect of the ventral cortex of the patella. Results for inflammatory factors showed that the blood levels of IL-6, IL-7, and TNF-α of the untreated control group were significantly higher than those of the treated group (P<0.05) 7–14 days posttreatment. The result of SEM showed that the cartilage neogenesis in the treated group had visible neonatal tissue and more irregular arrangement of new tissue fibers than that of the untreated control group. Furthermore, more vacuoles but without collagen fibers were observed in the cartilage of the untreated control group, and the thickness of the neogenetic cartilage in the treated group (65.13 ± 5.29, 65.30 ± 5.83) and the untreated control group (34.27 ± 5.42) showed a significant difference (P<0.01). Conclusion. Significantly higher improvement in cartilage neogenesis and recovery was observed in the treated group compared to the untreated control group. The joint fluid and the inflammatory response in the treated group decreased. Moreover, improved recovery in the neogenetic cartilage, damaged skin fascia, and muscle tissue around the joints was more significant in the treated group than in the untreated control group. In conclusion, canine UC-MSCs promote the repair of cartilage and patella injury in osteoarthritis, improve the healing of the surrounding tissues, and reduce the inflammatory response. https://www.hindawi.com/journals/sci/2018/1983025/