Background: Platelet-rich plasma (PRP) has been considered a promising tool for cartilage regeneration. However, increasing evidence has demonstrated the controversial effects of PRP on tissue regeneration, partially due to the unsatisfactory cell source. Chondrogenic progenitor cells (CPCs) have gained increasing attention as a potential cell source due to their self-renewal and multipotency, especially toward the chondrogenic lineage, and, thus, may be an appropriate alternative for cartilage engineering. Purpose: To compare the effects of PRP on CPC, mesenchymal stem cell (MSC), and chondrocyte proliferation, chondrogenesis, and cartilage regeneration. Study Design: Controlled laboratory study. Methods: Whole blood samples were obtained from 5 human donors to create PRPs (0, 1000 × 109, and 2000 × 109 platelets per liter). The proliferation and chondrogenesis of CPCs, bone marrow–derived MSCs (BMSCs), and chondrocytes were evaluated via growth kinetic and CCK-8 assays. Immunofluorescence, cytochemical staining, and gene expression analyses were performed to assess chondrogenic differentiation and cartilaginous matrix formation. The in vivo effects of CPCs, BMSCs, and chondrocytes on cartilage regeneration after PRP treatment were measured by use of histopathological, biochemical, and biomechanical techniques in a cartilage defect model involving mature male New Zealand White rabbits (critical size, 5 mm). Results: The CPCs possessed migration abilities and proliferative capacities superior to those of the chondrocytes, while exhibiting a chondrogenic predisposition stronger than that of the BMSCs. The growth kinetic, CCK-8, cytochemical staining, and biochemical analyses revealed that the CPCs simultaneously displayed a higher cell density than the chondrocytes and stronger chondrogenesis than the BMSCs after PRP stimulation. In addition, the in vivo study demonstrated that the PRP+CPC construct yielded better histological (International Cartilage Repair Society [ICRS] score, mean ± SEM, 1197.2 ± 163.2) and biomechanical (tensile modulus, 1.523 ± 0.194) results than the PRP+BMSC (701.1 ± 104.9, P < .05; 0.791 ± 0.151, P < .05) and PRP+chondrocyte (541.6 ± 98.3, P < .01; 0.587 ± 0.142, P < .01) constructs at 12 weeks after implantation. Conclusion: CPCs exhibit superiority over MSCs and chondrocytes in PRP scaffold-based cartilage regeneration, and PRP+CPC treatment may be a favorable strategy for cartilage repair. Clinical Relevance: These findings provide evidence highlighting the preferable role of CPCs as a cell source in PRP-mediated cartilage regeneration and may help researchers address the problem of unsatisfactory cell sources in cartilage engineering.

BackgroundShockwaves and mesenchymal stem cells (MSCs) have been widely accepted as useful tools for many orthopedic applications. However, the modulatory effects of shockwaves on MSCs remain controversial. In this study, we explored the influence of radial shockwaves on human bone marrow MSCs using a floating model in vitro and evaluated the healing effects of these cells on cartilage defects in vivo using a rabbit model.MethodsMSCs were cultured in vitro, harvested, resuspended, and treated with various doses of radial shockwaves in a floating system. Cell proliferation was evaluated by growth kinetics and Cell Counting Kit-8 (CCK-8) assay. In addition, the cell cycle and apoptotic activity were analyzed by fluorescence activated cell sorting. To explore the “stemness” of MSCs, cell colony-forming tests and multidifferentiation assays were performed. We also examined the MSC subcellular structure using transmission electron microscopy and examined the healing effects of these cells on cartilage defects by pathological analyses.ResultsThe results of growth kinetics and CCK-8 assays showed that radial shockwave treatment significantly promoted MSC proliferation. Enhanced cell growth was also reflected by an increase in the numbers of cells in the S phase and a decrease in the numbers of cells arrested in the G0/G1 phase in shockwave-treated MSCs. Unexpectedly, shockwaves caused a slight increase in MSC apoptosis rates. Furthermore, radial shockwaves promoted self-replicating activity of MSCs. Transmission electron microscopy revealed that MSCs were metabolically activated by shockwave treatment. In addition, radial shockwaves favored MSC osteogenic differentiation but inhibited adipogenic activity. Most importantly, MSCs pretreated by radial shockwaves exhibited an enhanced healing effect on cartilage defects in vivo. Compared with control groups, shockwave-treated MSCs combined with bio-scaffolds significantly improved histological scores of injured rabbit knees.ConclusionsIn the present study, we found that radial shockwaves significantly promoted the proliferation and self-renewal of MSCs in vitro and safely accelerated the cartilage repair process in vivo, indicating favorable clinical outcomes.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0805-5) contains supplementary material, which is available to authorized users.

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Level III, retrospective comparative study.

Background:Avascular necrosis of femoral head (AVNFH) typically presents in the young adults and progresses quickly without proper treatments. However, the optimum treatments for early stage of AVNFH are still controversial. This study was conducted to evaluate the therapeutic effects of multiple small-diameter drilling decompression combined with hip arthroscopy for early AVNFH compared to drilling alone.Methods:This is a nonrandomized retrospective case series study. Between April 2006 and November 2010, 60 patients (98 hips) with early stage AVNFH participated in this study. The patients underwent multiple small-diameter drilling decompression combined with hip arthroscopy in 26 cases/43 hips (Group A) or drilling decompression alone in 34 cases/55 hips (Group B). Patients were followed up at 6, 12, and 24 weeks, and every 6 months thereafter. Radiographs were taken at every follow-up, Harris scores were recorded at the last follow-up, the paired t-test was used to compare the postoperative Harris scores. Surgery effective rate of the two groups was compared using the Chi-square test.Results:All patients were followed up for an average of 57.6 months (range: 17–108 months). Pain relief and improvement of hip function were assessed in all patients at 6 months after the surgery. At the last follow-up, Group A had better outcome with mean Harris’ scores improved from 68.23 ± 11.37 to 82.07 ± 2.92 (t = −7.21, P = 0.001) than Group B with mean Harris’ scores improved from 69.46 ± 9.71 to 75.79 ± 4.13 (t = –9.47, P = 0.037) (significantly different: t = –2.54, P = 0.017). The total surgery effective rate was also significantly different between Groups A and B (86.0% vs. 74.5%; χ2 = 3.69, P = 0.02).Conclusion:For early stage of AVNFH, multiple small-diameter drilling decompression combined with hip arthroscopy is more effective than drilling decompression alone.

Although liver transplantation (LT) lengthens the survival time of patients with hepatocellular carcinoma (HCC), LT patients exhibit a high recurrence rate; particularly those that had advanced HCC associated with the tumor biological characteristics and long-term application of immunosuppressants. A consensus on optimal prophylaxis and treatment for recurrent HCC following LT does not currently exist. The present study retrospectively analyzed data from 36 non-University of California at San Francisco criteria-eligible patients with advanced HCC who underwent LT, and then treated them with sirolimus (SRL)-based therapy with thymalfasin and huaier granules (SRL+, n=18), or with tacrolimus-based therapy (controls; n=18). The SRL+ group had significantly longer recurrence times (P=0.008) and survival times (P<0.0001) (OS, 1-year: 100%, 3-year: 94.4%, 5-year: 77.8%; DFS, 1-year: 88.9%, 3-year: 55.6%, 5-year: 50.0%). Furthermore, compared with pre-LT values and the control group, the SRL+ group had significantly lower serum α-fetoprotein (AFP) levels (both P<0.0001) and percentage of Forkhead box P3 (FoxP3)+ Treg lymphocytes (P<0.001) during the first year. In the SRL+ group, FoxP3+/cluster of differentiation (CD)8+ Treg lymphocyte percentages decreased significantly following LT (P<0.001); however, CD8+/CD3+ T-cells significantly increased (P<0.001). Levels of serum AFP and FoxP3+ Treg cells increased when tumors relapsed, and decreased to near-normal when relapse foci were cured or stabilized. SRL+ therapy may decrease AFP and Treg levels, while increasing CD8+ T cells, indicating an associated mechanism among them. In conclusion, SRL+ therapy appears to be safe and effective in preventing HCC recurrence following LT with no significant adverse events, and warrants further investigation.

Rabbit mesenchymal stem cells (MSCs) are important seed cells in regenerative medicine research, particularly in translational research. In the current study, we showed that rabbit subchondral bone is a reliable source of MSCs. First, we harvested subchondral bone (SCB) from the rabbit knee-joint and initiated the MSC culture by cultivating enzyme-treated SCB. Adherent fibroblast-like cells that outgrew from SCB fulfill the common immuno-phenotypic criteria for defining MSCs, but with low contamination of CD45+ hematopoietic cells. Interestingly, differentiated SCB-MSCs expressed osteogenic and chondrogenic markers at significantly higher levels than those in bone marrow cell suspension-derived MSCs (BMS-MSCs) (P<0.05). No differences in the expression of adipogenic markers between SCB-MSC and BMS-MSC (P>0.05) were observed. Moreover, the results of the colony forming unit-fibroblast assay and sphere formation assay demonstrated that the SCB-MSCs had increased self-renewal potential. SCB-MSCs expressed higher levels of the stemness markers Nanog, OCT4, and Sox-2 compared to in BMS-MSCs (P<0.05). Furthermore, the results of both the CCK-8-based assay and CFSE dilution assay showed that SCB-MSCs exhibited enhanced proliferative capacity. In addition, SCB-MSCs exhibited higher phosphorylation of extracellular signal-related kinase/mitogen-activated protein kinase signaling, which is closely related to MSC proliferation. In conclusion, we identified SCB-MSCs as a novel stem cell population that met the requirements of MSCs; the unique properties of SCB-MSC are important for the potential treatment of tissue damage resulting from disease and trauma.

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