Purpose

The treatment of early degenerative processes affecting cartilage could prevent further aggravation and the onset of osteoarthritis (OA). The aim of the present study is to analyze the predicted potential of the micro RNAs (miRNAs) produced by cartilage cells (CCs), adipose- (ASCs) and bone marrow-derived (BMSCs) stem cells as a therapy to treat joint degeneration.

Methods and Materials

Articular cartilage, bone marrow and subcutaneous adipose tissue were collected from 3 patients who underwent total hip replacement. Cells were isolated, expanded and the supernatants were differentially centrifuged to obtain extracellular vesicles (EVs). Expression of EV-embedded miRNA were evaluated with the QuantStudio™ 12 K Flex OpenArray® platform. Mientournet and Ingenuity Pathway Analysis (IPA) were used for validated target prediction analysis and to identify miRNAs involved in OA and inflammation.

Results

Among the 428 analyzed miRNAs, 325 were expressed by all the cell populations, 26 shared by CCs and ASCs, 21 shared by CCs and BMSCs and 17 shared by ASCs and BMSCs. The miRNA selectively expressed only in one cell population were 16 by CCs, 12 by ASCs and 11 by BMSCs. Mienturnet revealed no results for miRNA selectively expressed by ASCs, whereas for CCs miR-17-3p, miR-25-5p, miR-200c-3p and miR-449a showed the highest number of interactions and putatively modulate cell cycle, senescence, apoptosis, Wnt, TGFβ, VEGF, Notch, Hippo, TNFα and IL-1β signaling. For BMSCs the highest number of interaction was showed by miR-141-3p, miR-143-5p, miR-363-3p, miR-205-5p and miR-483-3p involved in apoptosis, TGFβ, IGF-1, RUNX2 and endochondral ossification pathways. IPA analysis showed that many differently expressed miRNAs regulate macrophages and T cells activity, the expression of inflammatory mediators, cartilage homeostasis and cell proliferation.

Conclusion

Despite the need to be validated by functional tests, the predicted pathways identified in this study confirm and support the rationale behind the use of cell-based therapy for the treatment of degenerative joint conditions.

Purpose

The need to successfully treat the degenerative processes underlying knee osteoarthritis (OA) has led to develop one-step mesenchymal stem cells (MSCs)-based approaches. Adipose tissue micro-fragmentation (mFAT) allows to harvest quickly a relevant volume of minimally manipulated clusters containing MSCs.

The main purpose of this single-center, interventional, prospective, randomized, controlled study was to evaluate the efficacy of autologous mFAT in association or not with debridement arthroscopy (DA) for the treatment of severe knee OA.

Methods and Materials

A total of 78 patients (34 females, 44 males; mean age 60.7±7.9 y/o) were enrolled and randomly assigned to DA or DA + mFAT. A clinical visit, a MRI evaluation and the assessment of biochemical markers of collagen remodeling was performed before and 6 months after the treatment. Clinical-functional evaluations were conducted up to two years.

Results

The two groups demonstrated no randomization bias regarding age and gender distribution. At 6 months, higher improvements vs baseline were observed in patients treated with DA + mFAT compared to DA for KOOS and KSS-T, considering that the former had significantly worse baseline values.

Biochemical markers showed differences in the baseline values between the two groups, with higher levels of collagen degradation marker and lower levels of the synthesis marker in DA + mFAT in comparison with DA. In the whole cohort, the collagen synthesis marker showed a significant increase with respect to baseline, without relevant differences between groups. At a final follow up, patients in the DA + mFAT group showed a tendency for KOOS-PS improvements.

Conclusion

The mFAT injection improved functional outcomes in patients undergoing AD for knee OA. In fact, although both treatment groups showed a significant improvement, the DA + mFAT treatment showed to trigger a more consistent response.