We compared the clinical course of rotator cuff tears between rotator cuff exercise and bone marrow aspirate concentration (BMAC)-platelet rich plasma (PRP) injection to identify the therapeutic effects of BMAC-PRP on partial tear of the rotator cuff tendon. Twenty-four patients with partial tear of the rotator cuff tendon participated in this study. Twelve patients underwent extraction of BMACs and PRP and received the injection of BMAC-PRP at the tear site under ultrasound guidance. Twelve patients in the control group were asked to perform the rotator cuff exercise for 3 months. Visual analog scale (VAS) and manual muscle test (MMT) scores of the supraspinatus muscle were measured, and the American Shoulder and Elbow Surgeons (ASES) score was recorded before, 3 weeks, and 3 months after injection. Tear size was measured by the greatest longitudinal tear length. The change in the VAS differed between groups at 3 months (P = 0.039) but not at 3 weeks (P = 0.147). The ASES scores in the BMAC-PRP group changed from 39.4 ± 13.0 to 54.5 ± 11.5 at 3 weeks and 74.1 ± 8.5 at 3 months while those in the control group changed from 45.9 ± 12.4 to 56.3 ± 12.3 at 3 weeks (P = 0.712) and 62.2 ± 12.2 at 3 months (P = 0.011). The tear size decreased at 3 weeks or 3 months after the BMAC-PRP injection but was not significantly different from that in the control group. BMAC-PRP improved pain and shoulder function in patients with partial tear of the rotator cuff tendon. The patients were registered in the institutional board registry of Samsung Medical Center (registry number 2014-07-173 ).

Background: There are controversies about platelet-rich plasma (PRP) as an established treatment option for rotator cuff (RC) tendinopathy. The purpose of the study was to find the relation of cellular component with clinical efficacy in RC tendinopathy and to find the composition of PRP in treating RC tendinopathy.Methods: A total 30 patients were recruited and divided into PRP and control groups. In the PRP group, 2 ml of PRP solution was injected to the hypoechoic lesion of degenerative supraspinatus via 22-gauge syringe with peppering technique. Patients in the control group were taught rotator cuff strengthening exercises. American Shoulder and Elbow Surgeons (ASES), Constant-Murley score, and numeric rating scale (NRS) were measured before, 6 weeks after, 12 weeks after, and 24 weeks after the procedure. PRP compositions were analyzed using the 1 ml of PRP solution.Results: Linear regression analysis showed no significant difference of ASES and Constant-Murley scores between the groups at 6 weeks (P= 0.582 and 0.258) and at 12 weeks (P= 0.969 and 0.795) but showed a significant difference at 24 weeks (P= 0.050 and 0.048). Independentttest showed significant group difference of NRS at 6 weeks (P= 0.031) but not at 12 and 24 weeks (P= 0.147 and 0.935). 5.19 pg/ml in IL-1β and 61.79 μg/ml in TGF-β1 were acquired as cutoff values to predict meaningful improvement. The PRP subgroup above IL-1β or TGF-β1 cutoff value showed significant differences in all clinical outcomes compared with the exercise group while the PRP subgroup below the cutoff value showed no significant differences in linear regression analysis.Conclusions: Our study can help to find the optimal PRP condition and to enhance the effect of PRP on RC tendinopathy.Trial registration: All the patients were registered in our Institutional Ethics Committee (approval number2014-05-009).

The aim of this study was to evaluate the therapeutic effects and mechanisms of Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) in an animal model of Duchenne muscular dystrophy (DMD). Mdx mice (3–5 months old) were administered five different doses of WJ-MSCs through their tail veins. A week after injection, grip strength measurements, creatine kinase (CK) assays, immunohistochemistry, and western blots were performed for comparison between healthy mice, mdx control mice, and WJ-MSC-injected mdx mice. WJ-MSCs exerted dose-dependent multisystem therapeutic effects in mdx mice, by decreasing CK, recovering normal behavior, regenerating muscle, and reducing apoptosis and fibrosis in skeletal muscle. We also confirmed that miR-499-5p is significantly downregulated in mdx mice, and that intravenous injection of WJ-MSCs enhanced its expression, leading to anti-fibrotic effects via targeting TGFβR 1 and 3. Thus, WJ-MSCs may represent novel allogeneic “off-the-shelf” cellular products for the treatment of DMD and possibly other muscle disorders.

Mesenchymal stem cells (MSCs) are effective therapeutic agents that contribute to tissue repair and regeneration by secreting various factors. However, donor-dependent variations in MSC proliferation and therapeutic potentials result in variable production yields and clinical outcomes, thereby impeding MSC-based therapies. Hence, selection of MSCs with high proliferation and therapeutic potentials would be important for effective clinical application of MSCs. This study is aimed at identifying the upregulated genes in human Wharton’s jelly-derived MSCs (WJ-MSCs) with high proliferation potential using mRNA sequencing. Aurora kinase A (AURKA) and dedicator of cytokinesis 2 (DOCK2) were selected as the upregulated genes, and their effects on proliferation, migration, and colony formation of the WJ-MSCs were verified using small interfering RNA (siRNA) techniques. mRNA expression levels of both the genes were positively correlated with the proliferation capacity of WJ-MSCs. Moreover, AURKA from human WJ-MSCs regulated the antiapoptotic effect of skeletal muscle cells by upregulating the chemokine (C motif) ligand (XCL1); this was further confirmed in the mdx mouse model. Taken together, the results indicated that AURKA and DOCK2 can be used as potential biomarkers for proliferation and migration of human WJ-MSCs. In particular, human WJ-MSCs with high expression of AURKA might have therapeutic efficacy against muscle diseases, such as Duchenne muscular dystrophy (DMD).

Replicative senescence of mesenchymal stem cells (MSCs) caused by repeated cell culture undermines their potential as a cell therapy because of the reduction in their proliferation and therapeutic potential. Glutaminase-1 (GLS1) is reported to be involved in the survival of senescent cells, and inhibition of GLS1 alleviates age-related dysfunction via senescent cell removal. In the present study, we attempted to elucidate the association between MSC senescence and GLS1. We conducted in vitro and in vivo experiments to analyze the effect of GLS1 inhibition on senolysis and the therapeutic effects of MSCs. Inhibition of GLS1 in Wharton’s jelly-derived MSCs (WJ-MSCs) reduced the expression of aging-related markers, such as p16, p21, and senescence-associated secretory phenotype genes, by senolysis. Replicative senescence-alleviated WJ-MSCs, which recovered after short-term treatment with bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES), showed increased proliferation and therapeutic effects compared to those observed with senescent WJ-MSCs. Moreover, compared to senescent WJ-MSCs, replicative senescence-alleviated WJ-MSCs inhibited apoptosis in serum-starved C2C12 cells, enhanced muscle formation, and hindered apoptosis and fibrosis in mdx mice. These results imply that GLS1 inhibition can ameliorate the therapeutic effects of senescent WJ-MSCs in patients with muscle diseases such as Duchenne muscular dystrophy. In conclusion, GLS1 is a key factor in modulating the senescence mechanism of MSCs, and regulation of GLS1 may enhance the therapeutic effects of senescent MSCs, thereby increasing the success rate of clinical trials involving MSCs.