Discussion
inflammation, pain, OA, KOA
PROLIFERATION, INFLAMMATION, OSTEOARTHRITIS KNEE, PATHOGENESIS, WORMS, KNEE OSTEOARTHRITIS, DISEASES, INFLAMMATORY DISEASE
The present study investigated the safety and efficacy of intra-articular injection of allogeneic AD-MSCs in KOA by the assessment of clinical outcomes, MRI, some serum biomarkers, and cell CD markers in peripheral blood samples. Clinical outcome measures showed improvement in AD-MSCs group.Knee osteoarthritis is the most prevalent type of OA which has a distinct effect on the global health status [WOMAC, KOOS, VAS, and SF-36 are the most common questionnaires available to evaluate the effectiveness of treatment modalities in patients with KOA [WOMAC is one of the most common questionnaires used in similar studies [In KOOS, contrary to WOMAC, the lower score describes the worse health status of the patient. The results of our study showed a noticeable increase in the scores of all subgroups (symptoms, pain, daily function, sport and recreation, and quality of life), in the AD-MSCs injected group during the 1-year follow-up. This increasing trend was significant, while in the control group, despite a slight increase after 3 months, at the end of 12 months, no significant changes were observed compared with the baseline.According to the VAS results, the severity of pain indicated by the patients in AD-MSCs group during the 1-year follow-up showed a decreasing trend, and this reduction was noticeable. A meta-analysis of nine randomized controlled trials with 476 patients evaluated pain level and functionality improvement after intra-articular injection of MSCs in KOA. The results of this study indicated that transplantation of MSCs significantly reduced the VAS score during the long-term follow-up [According to the assessment of SF-36, the condition of the patients who received AD-MSCs was improved significantly, and this improvement was remarkable in all subgroups of the SF-36.Assessment of the questionnaire-based outcomes indicated almost the same trend during the 12-month follow-up in similar studies. The highest rate of improvement was observed 3 months post-injection then plateaued between 6 and 12 months after AD-MSCs injection. The observed trend in this study was the same as the other studies. For example, the WOMAC and KOOS outcomes in the study conducted by Freitag et al. followed a similar trend. They used single and double doses of 100 × 10MRI findings demonstrated thickness alteration in 12 different points of the femoral and tibial articular cartilage. These 12 points of articular cartilage were selected according to the cartilage areas assessed in whole-organ magnetic resonance imaging score (WORMS) in KOA [Also, articular cartilage evaluation by MRI has considered in the similar randomized trials by the use of common scoring systems. For instance, in 2019, after intra-articular injection of autologous AD-MSCs, researchers examined the modification of articular cartilage based on MRI osteoarthritis knee scores (MOAKS) between two treatment groups (a single dose of 100 × 10Assessment of biological markers is indicated for the early diagnosis of inflammatory diseases such as OA, and also for monitoring the potency of the treatment methods [In addition, the expression level of HA in AD-MSCs group diminished significantly and the average serum level of HA among the patients who received AD-MSCs injection, decreased by 47.18% after 3 months compared with the baseline. The correlation between serum HA concentration and OA has been evidenced in numerous literatures [Matrix metalloproteinase-3 (MMP-3) is another early KOA biomarker investigated in this study. Despite a slight decrease in the concentration of MMP-3 in the AD-MSCs group after 3 months, any significant difference was not reported between AD-MSCs and control group. The results of some studies conducted for the assessment of any association between MMP-3 level and OA severity indicated that the elevated level of MMP-3 correlates with severe OA [The serum level of IL-6, an upstream pro-inflammatory cytokine with complex roles in diseases with inflammatory background, was declined after MSCs transplantation in consequence of modulating immune system [Interleukin-10 is the other inflammatory cytokine which MSC therapy affects its secretion. The IL-10 expression increased by MSCs in order to reduce the proliferation of T cells to modulate the immune system. This anti-inflammatory cytokine along with other markers such as TGF-β1 plays a crucial role in the regulation of immune system by inhibition of lymphocytes proliferation and maturation of dendritic cells [To show that if AD-MSCs can lead to the reduction of inflammation in KOA, the percentage of cells expressing CD3, CD4, CD8 and CD25 was analyzed in blood. These CD markers may be suggested as additional inflammatory indicators in OA, due to the recent reports that elucidate T helper (Th) cells which are involved in the pathogenesis of OA [In our study, the results of the evaluation of CD3, CD4, and CD8 in the blood serum of patients who received AD-MSCs had almost followed a similar decreasing trend at different time points during the 6-month follow-up. A dramatic reduction in the percentages of cells expressing these markers accrued after 1 week due to the immune-regulatory features of AD-MSCs. Then, approximately a plateau has been observed in the trend of these markers during 6-month follow-up. The expression level of each of these markers reached a relatively stable values, which were well below the baseline levels between 3 and 6 months after injection. This decrease in the expression of the mentioned cell surface markers 6 months post-injection in the AD-MSCs group, compared with the baseline levels, can be attributed to the alleviation of KOA-induced inflammation. While in the control group, the levels of CD3 and CD8 were almost constant during the 6 months, the percentage of CD4The results of our study showed that single intra-articular injection of 100 × 10