Attenuation of osteoarthritis progression through intra-articular injection of a combination of synovial membrane-derived MSCs (SMMSCs), platelet-rich plasma (PRP) and conditioned medium (secretome).

PURPOSE: Osteoarthritis (OA) as a progressive destructive disease of articular cartilage is the most common joint disease characterized by reduction of joint cartilage thickness, demolition of cartilage surface and new bone formation. To overcome these problems, the purpose of the current research was to evaluate and compare the in vivo effects of synovial membrane-derived mesenchymal stem cell (SMMSCs), platelet-rich plasma (PRP) and conditioned medium (secretome) on collagenase II-induced rat knee osteoarthritis (KOA) remedy. METHODS: For the first step, SMMSCs were isolated and characterized. Also, secretome was collected from SMMSCs culture. Furthermore, PRP was collect from the rat heart venous blood. Second, two injection of collagenase II with an interval of 3 days was performed in the knee intra-articular space to induce osteoarthritis. Two weeks later, animals were randomly divided into 6 groups. Control group without treatment, positive group: taken an intra-articular sodium hyaluronate injection (0.1 ml), treatment groups taken an intra-articular injection of; treatment 1: SMMSCs (5 × 106), treatment 2: SMMSCs (5 × 106)/secretome (50 µl), treatment 3: SMMSCs (5 × 106)/PRP (50 µl), and treatment 4: SMMSCs (5 × 106)/ secretome (50 µl)/ PRP (50 µl). Three months later, rats were killed and the following assessments were executed: radiography, histopathology, and immunohistochemistry. RESULTS: Our findings represented that a combination of the SMMSCs/secretome/PRP had a considerable effect on glycosaminoglycans (GAGs) and collagen II contents, articular cartilage preservation, compared with other groups. In addition, combination of the SMMSCs with PRP and secretome showed the lowest expression of mmp3, while SOX9 had the highest expression in comparison with other groups. Also, SMMSCs-injected groups demonstrated better results compared with positive and control groups. CONCLUSIONS: Injecting a combination of the SMMSCs/secretome/PRP resulted in better efficacy in terms of joint space width, articular cartilage surface continuity and integrity, sub-chondral bone and ECM constituents such as collagen II. Indeed, transplantation of this combination could be considered as a preliminary therapy for clinical trial study in the future.

Are Stem Cells Derived from Synovium and Fat Pad Able to Treat Induced Knee Osteoarthritis in Rats?

BACKGROUND: Osteoarthritis (OA) is a chronic disease and a significant cause of joint pain, tenderness, and limitation of motion. At present, no specific treatment is available, and mesenchymal stem cells (MSCs) have shown promising potentials in this regard. Herein, we aimed to evaluate the repairing potentials of stem cells derived from the synovium and fat pad in the treatment of OA. METHODS: Twenty-eight male rats (220 ± 20 g, aged 10-12 weeks), were randomly divided into four groups (n = 7): C1: nontreated group, C2: Hyalgan-treated group, E1: adipose tissue-derived stem cell-treated group, and E2: synovial membrane-based stem cell-treated group. Collagenase type II was injected into the left knee; after eight weeks, OA was developed. Then, stem cells were injected, and rats were followed for three months. Afterward, specimens and radiological images were investigated. p value ≤ 0.05 was set as statistically significant. RESULTS: Compared to the C1 group, the E1 and E2 groups showed significantly better results in all six pathological criteria as well as joint space width and osteophytes of medial tibial, medial femoral, and medial fabellar condyles (p ≤ 0.001). Similarly, compared to the C2 group, the E1 and E2 groups had better scores regarding surface, matrix, cell distribution, and cell population viability (p < 0.05). E2 showed considerably higher scores compared to C2 regarding subchondral bone and cartilage mineralization (p < 0.05). The joint space width was similar between the C2 and E groups. CONCLUSION: Treatment of OA with MSCs, particularly synovial membrane-derived stem cells, not only prevented but also healed OA of the knee to some extent in comparison to the Hyalgan and nontreatment groups.

Verapamil, a Calcium-Channel Blocker, Improves the Wound Healing Process in Rats with Excisional Full-Thickness Skin Wounds Based on Stereological Parameters.

OBJECTIVE: Calcium can play noticeable roles in the wound-healing process, such as its effects on organization of F-actinin collagen bundles by fibroblasts at the injury site. In addition, calcium-channel blockers such as verapamil have antioxidant activity by increasing nitric oxide production that promotes angiogenesis, proliferation of fibroblasts, and endothelial cells in the skin-regeneration process. Therefore, in this study, the authors' objective was to investigate the effects of verapamil on the process of wound healing in rat models according to stereological parameters. MATERIALS AND METHODS: In this experimental study, 36 male Wistar rats were randomly divided into 3 groups (n = 12): the control group that received no treatment, gel-base-treated group, and the 5% verapamil gel-treated group. Treatments were done every 24 hours for 15 days. Wound closure rate, volume densities of the collagen bundles and the vessels, vessel's length density and mean diameter, and fibroblast populations were estimated using stereological methods and were analyzed by the Kruskal-Wallis and Mann-Whitney U tests; P < .05 was considered statistically significant. RESULTS: The verapamil-treated group showed a faster wound closure rate in comparison with control and gel-base groups (P = .007 and P = .011). The numerical density of fibroblasts, volume density of collagen bundles, mean diameter, and volume densities of the vessels in the verapamil group were significantly higher than those in the control and the base groups (P < .005). CONCLUSIONS: The authors showed that verapamil has the ability to improve wound healing by enhancing fibroblast proliferation, collagen bundle synthesis, and revascularization in skin injuries.

Scrotal Cooling to Protect Against Cisplatin-induced Spermatogenesis Toxicity: Preliminary Outcome of an Experimental Controlled Trial.

OBJECTIVE: To investigate the protective effects of scrotal cooling on cisplatin-induced gonadal toxicity in an animal model. METHODS: Twenty-one male BALB/c mice were divided into 3 groups. The cisplatin group received 2 cycles of cisplatin (2.5 mg/kg/day for 5 days with 16 days of recovery) intraperitoneally, and the cisplatin + cooling group received the same regimen of cisplatin with a cooling protocol: cooling induction for 30 minutes before injection and cooling for 60 minutes after injection. Mice in control group were given an injection of 2 mL normal saline intraperitoneally. After 35 days of recovery (1 cycle of spermatogenesis), the volume of the testes (Cavalieri method), volume density of the tubules and epithelium (point-counting method), and number of cells (optical dissector method) were estimated. RESULTS: The volume of the testes, tubules, and epithelium was reduced between 61% and 66%, and the number of the spermatogonia, spermatocytes, round spermatids, and long spermatids was reduced between 70% and 93% in cisplatin group compared with that of control mice. Cisplatin affected spermatids to a greater extent, and Sertoli cells to a lesser extent than the other cells. The volume and number of the cells were reduced in the cisplatin + cooling group but to a lesser extent compared with those of mice in the cisplatin group. Sertoli cells were more intact in the cisplatin + cooling group compared with those of the control group. CONCLUSION: Scrotal cooling during cisplatin administration seems to have beneficial effects on spermatogenesis. Scrotal cooling may hold promise as a way to protect fertility.