Potential for Tumorigenesis and Repair of Osteochondral Defects by iPS Cell Transplantation in Rat

Abstract Articular cartilage repair remains a challenge in the field of orthopedic medicine. Cell-based therapy for cartilage repair, such as autologous chondrocyte implantation, was established in the 1990s. However, the issue of the source from which the lesion-targeting cells are harvested remains a limitation of this approach as larger lesions require more cells for repair, and thus, more healthy tissue must be damaged to harvest the needed cells. Reprogramming of induced pluripotent stem (iPS) cells is a promising tool for cell-based regenerative therapy because of their proliferative capacity and pluripotency; however, these characteristics also create a risk of tumorigenesis. This study aimed to determine the probability of iPS cell-derived tumor occurrence as a function of injection or transplantation site, and to assess whether transplanted iPS cells can promote cartilage defect repair. Pluripotent mouse iPS cells (5x10 6 cells/ml) were subcutaneously injected or transplanted into experimentally induced lesions in the knee cartilage of immunodeficient rats. Subcutaneous teratoma formation was observed in 30% of animals (3 of 10) at 4weeks, and 41% of animals (7 of 17) at 12 weeks after iPS cell injection. Cartilage repair as indicated by modified Wakitani's score was similar in the cell-free group and in the iPS cell implantation group at 4 weeks [11.8 ± 1.8 (n = 8) vs. 10.3 ± 2.8 (n = 18)]. iPS cell implantation yielded a score of 7.8 ± 2.0 (n = 10) at 12 weeks, significantly better than the cell-free group [10.5 ± 0.6 (n = 4)]. There was no macro-or microscopic evidence of tumor formation at the cartilage repair site after iPS cell implantation. Although we could not use the iPS cells directly for cartilage repair, the results of our study indicate the potential for a new therapy for cartilage repair by developing iPS reprogramming technology

Analyses of associated factors with concomitant meniscal injury and irreparable meniscal tear at primary anterior cruciate ligament reconstruction in young patients

Purpose:: Although several factors related to the concomitant meniscal injury at anterior cruciate ligament reconstruction (ACL-R) have been investigated in a general population, few studies have identified the risk factors of meniscal tear severity in young patients in which the majority of ACL tears occur. The purpose of this study was to analyze the associated factors with meniscal injury and irreparable meniscal tear and the timeline for medial meniscal injury at ACL-R in young patients. Methods:: A retrospective analysis of young patients (13 to 29 years of age) who underwent ACL-R by a single surgeon from 2005 to 2017 was conducted. Predictor variables (age, sex,body mass index [BMI], time from injury to surgery [TS], and pre-injury Tegner activity level) for meniscal injury and irreparable meniscal tear were analyzed with multivariate logistic Results:: Four hundred and seventy-three consecutive patients with an average of 31.2 months post-operative follow-up were enrolled in this study. The risk factors for medial meniscus injury were TS (<= 3 months) (odds ratio [OR], 3.915; 95% CI, 2.630-5.827; P < .0001) and higher BMI (OR, 1.062; 95% CI, 1.002-1.125; P = 0.0439). The presence of irreparable medial meniscal tears correlated with higher BMI (OR, 1.104; 95% CI, 1.011-1.205; P = 0.0281) Conclusion: An increased time from ACL tear to surgery of 3 months was strongly associated with an increased risk of medial meniscus injury, but not related to irreparable medial meniscal tear at primary ACL reconstruction in young patients. Level of Evidence: Level IV

The effect and safety of periarticular multimodal drug injection without morphine and epinephrine in anterior cruciate ligament reconstruction

Background Periarticular multimodal drug injection (PMDI) is a safe and effective pain management technique after anterior cruciate ligament reconstruction (ACLR); however, adding morphine and epinephrine sometimes causes adverse effects. Therefore, we evaluated the efficacy of PMDI without morphine and epinephrine after ACLR. Methods This retrospective matched case-control study included patients who had undergone primary double-bundle ACLR with PMDI and were then matched one-to-one with a control group without PMDI based on sex, age, and body mass index using propensity-matched analysis. The following clinical outcomes were compared between the groups: visual analog scale (VAS) score, C-reactive protein (CRP) concentration, number of times the patients used additional analgesics, complication rate, and postoperative time to achieve straight leg raise (SLR). Results Twenty-nine patients with PMDI and 29 controls were enrolled. The VAS score at 1 day postoperatively was lower in the PMDI than the control group (1.93  ±  1.44 vs. 3.41  ±  1.75, respectively; P  < 0.001). The CRP concentration at 1 and 3 days was lower in the PMDI than the control group (0.46  ±  0.47 vs. 1.00  ±  0.69 mg/dL, P  < 0.001; and 1.93  ±  1.71 vs. 4.01  ±  2.55 mg/dL, P  < 0.001, respectively). The average number of additional analgesics used was significantly lower in the PMDI than the control group. There were no significant differences in the frequency of occurrence of postoperative complications between the two groups. The number of patients who could achieve SLR within 1 day was 27/29 (93%) in PMDI group, which was significantly higher than the control group (12/29, 41%) ( P  < 0.001). Conclusion PMDI without morphine and epinephrine after ACLR reduced patients’ subjective pain level, objective inflammatory response without complications and enabled patients to achieve early functional recovery