METHODS: Literature searches were carried out on "Scopus", "PubMed" and "Google Scholar" up to September 2022 to find relevant articles in the English language for the scope of this review.
RESULTS: Recent evidence showed a significant role of ADSC therapies in DM by ameliorating insulin resistance and hyperglycemia, regulating hepatic glucose metabolism, promoting β cell function and regeneration, and functioning as a gene delivery tool. In addition, ADSCs could improve diabetic wound healing by promoting collagen deposition, inhibiting inflammation, and enhancing angiogenesis.
CONCLUSION: Overall, this literature review revealed the great clinical implications of ADSCs for translating into the clinical setting for the treatment of diabetes. However, further large-scale and controlled studies are needed to overcome challenges and confirm the safety and optimal therapeutic scheme before daily clinical application.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-023-01280-8.
METHODS: Patients with primary hip and knee OA were recruited, and 3 mL of bone marrow was harvested during joint replacement surgery. Bone marrow stromal cells (BMSC) was isolated and cultured in a culture flask for three passages. Later experiment was then sub-cultured in a well plate labeled as the control group and H2O2 (0.1 mM) treated group. ProcartaPlex® Multiplex Immunoassay was performed to measure cytokine levels produced by the BMSC at 0 h, as well as 72 h.
RESULTS: Cytokines such as tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-1β generally exhibited higher cytokine levels in subjects with DM than in nonDM subjects at 0 and 72 h. For IL-17, its expression was similar in nonDM and DM groups at 0 and 72 h. Cytokine IL-10 showed no significant difference in both the groups while DM and nonDM groups treated with H2O2 showed decreased IL-4 levels compared to control groups at 72 h. Bone marrow cells from DM-OA are more vulnerable to chemical insult and are associated with higher levels of proinflammatory cytokines production and lower IL-4 level production.
CONCLUSIONS: This study provides a clue that management of OA with co-morbidity like DM needs future studies.
DESIGN: Forty-two Sprague Dawley rats were divided into 2 groups: the ACLT group and the nonoperated control group. Surgery was conducted on the ACLT group, and subsequently rats from both groups were sacrificed at 1, 2, and 3 weeks postsurgery. Subchondral bone was evaluated using a high-resolution peripheral quantitative computed tomography scanner, while cartilage was histologically evaluated and scored.
RESULTS: A significant reduction in the subchondral trabecular bone thickness and spacing was found as early as 1 week postsurgery in ACLT rats compared with the nonoperated control. This was subsequently followed by a reduction in bone mineral density and bone fractional volume at week 2, and finally a decrease in the trabecular number at week 3. These changes occurred together with cartilage degeneration as reflected by an increasing Mankin score over all 3 weeks.
CONCLUSIONS: Significant changes in subchondral bone occur very early in OA concurrent with surface articular cartilage degenerative change suggest that factors affecting bone remodeling and resorption together with cartilage matrix degradation occur very early in the disease.
METHODS: The proximal tibia was resected as a single osteochondral unit during total knee replacement from patients (N = 10). The osteoarthritic chondrocytes were isolated from the osteochondral units, and characterized using reverse transcriptase-polymerase chain reaction. The isolated osteoarthritic chondrocytes were cultured and embedded in agarose, and then subjected to 10% and 20% uniaxial dynamic compression up to 8-days using a bioreactor. The morphological features and changes in the osteoarthritic chondrocytes upon compression were evaluated using scanning electron microscopy. Safranin O was used to detect the presence of cartilage matrix proteoglycan expression while quantitative analysis was conducted by measuring type VI collagen using an immunohistochemistry and fluorescence intensity assay.
FINDINGS: Gene expression analysis indicated that the isolated osteoarthritic chondrocytes expressed chondrocyte-specific markers, including BGN, CD90 and HSPG-2. Moreover, the compressed osteoarthritic chondrocytes showed a more intense and broader deposition of proteoglycan and type VI collagen than control. The expression of type VI collagen was directly proportional to the duration of compression in which 8-days compression was significantly higher than 4-days compression. The 20% compression showed significantly higher intensity compared to 10% compression in 4- and 8-days.
INTERPRETATION: The biosynthetic activity of human chondrocytes from osteoarthritic joints can be enhanced using selected compression regimes.
METHODS: 20-Plex proteins were quantified using Human Magnetic Luminex® assay (R&D Systems, USA) from plasma and SF of OA (n = 14) and non-OA (n = 14) patients. Ingenuity Pathway Analysis (IPA) software was used to predict the relationship and possible interaction of molecules pertaining to OA.
RESULTS: There were significant differences in plasma level for matrix metalloproteinase (MMP)-3, interleukin (IL)-27, IL-8, IL-4, tumour necrosis factor-alpha, MMP-1, IL-15, IL-21, IL-10, and IL-1 beta between the groups, as well as significant differences in SF level for IL-15, IL-8, vascular endothelial growth factor (VEGF), MMP-1, and IL-18. Our predictive OA model demonstrated that toll-like receptor (TLR) 2, macrophage migration inhibitory factor (MIF), TLR4 and IL-1 were the main regulators of IL-1B, IL-4, IL-8, IL-10, IL-15, IL-21, IL-27, MMP-1 and MMP-3 in the plasma system; whilst IL-1B, TLR4, IL-1, and basigin (BSG) were the regulators of IL-4, IL-8, IL-10, IL-15, IL-18, IL-21, IL-27, MMP-1, and MMP-3 in the SF system.
CONCLUSION: The elevated plasma IL-8 and SF IL-18 may be associated with the pathogenesis of OA via the activation of MMP-3.
Methods: One hundred clinical computed tomography (CTs) of adult pelvises (male n = 50, female n = 50) of Malay, Chinese and Indian descent were acquired. CTs were segmented and defined landmarks were placed. Three 3D statistical pelvic model and mean models (overall, male, female) were generated. Anatomical variations were analysed using principal component analysis. To measure gender-related differences and differences to the existing ABM, distances between the anterior superior iliac spines (ASIS), the anterior inferior iliac spines (AIIS), the promontory and the symphysis (conjugate vera, CV) as well as the ischial spines (diameter transversa, DT) were quantified.
Results: Principal component analysis displayed large variability regarding the pelvic shape and size. Female and male statistical models were similar in ASIS (225 ± 20; 227 ± 13 mm; P = 0.4153) and AIIS (185 ± 11; 187 ± 10 mm; P = 0.3982) and differed in CV (116 ± 10; 105 ± 10 mm; P
Methods: hTenowere isolated from human hamstring tendon. Presence of insulin receptor beta (INSR-β) on normal tendon tissues and the hTeno monolayer culture were analyzed by immunofluorescence staining. The presence of Glucose Transporter Type 1 (GLUT1) and Glucose Transporter Type 4 (GLUT4) on the hTeno monolayer culture were also analyzed by immunofluorescence staining. Primary hTeno were treated with 0.008, 0.08, 0.8 and 8.0 µM of TNF-α, with and without insulin supplement. Outcome measures include 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) assay to determine the glucose uptake activity; colourimetric total collagen assay to quantify the total collagen expression levels; COL-I ELISA assay to measure the COL-I expression levels and real-time qPCR to analyze the mRNA gene expressions levels of Scleraxis (SCX), Mohawk (MKX), type I collagen (COL1A1), type III collagen (COL3A1), matrix metalloproteinases (MMP)-9 and MMP-13 in hTeno when treated with TNF-α. Apoptosis assay for hTeno induced with TNF-α was conducted using Annexin-V FITC flow cytometry analysis.
Results: Immunofluorescence imaging showed the presence of INSR-β on the hTeno in the human Achilles tendon tissues and in the hTeno in monolayer culture. GLUT1 and GLUT4 were both positively expressed in the hTeno. TNF-α significantly reduced the insulin-mediated 2-NBDG uptake in all the tested concentrations, especially at 0.008 µM. Total collagen expression levels and COL-I expression levels in hTeno were also significantly reduced in hTeno treated with 0.008 µM of TNF-α. The SCX, MKX and COL1A1 mRNA expression levels were significantly downregulated in all TNF-α treated hTeno, whereas the COL3A1, MMP-9 and MMP-13 were significantly upregulated in the TNF-α treated cells. TNF-α progressively increased the apoptotic cells at 48 and 72 h.
Conclusion: At 0.008 µM of TNF-α, an IR condition was induced in hTeno, supported with the significant reduction in glucose uptake, as well as significantly reduced total collagen, specifically COL-I expression levels, downregulation of candidate tenogenic markers genes (SCX and MKX), and upregulation of ECM catabolic genes (MMP-9 and MMP-13). Development of novel IR model in hTeno provides an insight on how tendon homeostasis could be affected and can be used as a tool for further discovering the effects on downstream molecular pathways, as the implication for diabetic tendinopathy.