Makoto Nishimori

Biomechanical Function of Anterior Cruciate Ligament Remnants: How Long Do They Contribute to Knee Stability After Injury in Patients With Complete Tears?

PURPOSE This study aimed to evaluate the biomechanical function of anterior cruciate ligament (ACL) remnants in anteroposterior and rotational knee stability in patients with a complete ACL injury. METHODS ACL remnants were classified into 5 morphologic patterns: group 1, bridging between the posterior cruciate ligament and tibia; group 2, bridging between the intercondylar notch and tibia; group 3, partial rupture of the posterolateral bundle; group 4, partial rupture of the anteromedial bundle; and group 5, no substantial ACL remnants. The decision of whether the remaining bundle represented partial or complete rupture of the ACL was made based on physical, magnetic resonance imaging, and arthroscopic findings in a comprehensive manner. Patients in groups 1 (n = 18) and 2 (n = 12) underwent intraoperative arthrometry with a navigation system before and immediately after resection of the ACL remnant. The effects of chronicity (duration between injury and surgery) and ACL remnant pattern on changes in knee laxity after debridement of the ACL remnant were investigated. RESULTS Chronicity had a significant effect on changes in anteroposterior knee laxity evaluated at 30° of knee flexion after resection of the ACL remnant (change in laxity of 2.22 mm for chronicity ≤1 year and 0.17 mm for chronicity >1 year). Chronicity did not influence changes in rotational knee stability after resection of the remnant. There were no significant differences between groups 1 and 2 with regard to any of the evaluated changes in knee stability. CONCLUSIONS In groups 1 and 2 ACL remnants contributed to anteroposterior knee stability evaluated at 30° of knee flexion for up to 1 year after injury, beyond which this biomechanical function was lost. Chronicity and remnant pattern did not influence changes in rotational knee stability after resection of the remnant. LEVEL OF EVIDENCE Level III, diagnostic study of nonconsecutive patients.

Repair of chronic osteochondral defects in the rat : A bone marrow-stimulating procedure enhanced by cultured allogenic bone marrow mesenchymal stromal cells

Bone marrow mesenchymal stromal cells were aspirated from immature male green fluorescent protein transgenic rats and cultured in a monolayer. Four weeks after the creation of the osteochondral defect, the rats were divided into three groups of 18: the control group, treated with an intra-articular injection of phosphate-buffered saline only; the drilling group, treated with an intra-articular injection of phosphate-buffered saline with a bone marrow-stimulating procedure; and the bone marrow mesenchymal stromal cells group, treated with an intra-articular injection of bone marrow mesenchymal stromal cells plus a bone marrow-stimulating procedure. The rats were then killed at 4, 8 and 12 weeks after treatment and examined. The histological scores were significantly better in the bone marrow mesenchymal stromal cells group than in the control and drilling groups at all time points (p < 0.05). The fluorescence of the green fluorescent protein-positive cells could be observed in specimens four weeks after treatment.

Therapeutic potential of anterior cruciate ligament-derived stem cells for anterior cruciate ligament reconstruction.

We recently reported that the ruptured regions of the human anterior cruciate ligament (ACL) contained vascular-derived stem cells, which showed the potential for high expansion and multilineage differentiation. In this study, we performed experiments to test the hypothesis that ACL-derived CD34+ cells could contribute to tendon–bone healing. ACL-derived cells were isolated from the rupture site of human ACL by fluorescence-activated cell sorting. Following ACL reconstruction, immunodeficient rats received intracapsular administration of either ACL-derived CD34+ cells, nonsorted (NS) cells, CD34- cells, or phosphate-buffered saline (PBS). We also performed in vitro cell proliferation assays and enzyme-linked immunosorbent assays for vascular endothelial growth factor (VEGF) secretion. We confirmed the recruitment of the transplanted cells into the perigraft site after intracapuslar injection by immunohistochemical staining at week 1. Histological evaluation showed a greater area of collagen fiber formation and more collagen type II expression in the CD34+ group than the other groups at the week 2 time point. Immunostaining with isolectin B4 and rat osteocalcin demonstrated enhanced angiogenesis and osteogenesis in the CD34+ group at week 2. Moreover, double immunohistochemical staining for human-specific endothelial cell (EC) and osteoblast (OB) markers at week 2 demonstrated a greater ability of differentiation into ECs and OBs in the CD34+ group. Microcomputerized tomography showed the greatest healing of perigraft bone at week 4 in the CD34+ cell group, and the failure load of tensile test at week 8 demonstrated the greatest biomechanical strength in the CD34+ group. Furthermore, the in vitro studies indicated that the CD34+ group was superior to the other groups in their cell proliferation and VEGF secretion capacities. We demonstrated that ACL-derived CD34+ cells contributed to the tendon–bone healing after ACL reconstruction via the enhancement of angiogenesis and osteogenesis, which also contributed to an increase in biomechanical strength.

Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament

We performed this study to investigate the therapeutic role of vascular endothelial growth factor (VEGF) in medial collateral ligament (MCL) healing. Murine muscle derived stem cells (MDSCs) obtained via the preplate technique were retrovirally transduced to express: (1) VEGF and nLacZ (MDSC‐VEGF), (2) soluble fms‐like tyrosine kinase‐1 (sFLT1, a VEGF‐specific antagonist) and nLacZ (MDSC‐sFLT1), and (3) nLacZ (MDSC‐nLacZ). After transecting the MCL of immunodeficient rats, 5 × 105 cells of each of the transduction groups list above were transplanted into the MCL injury site. A control group was injected with phosphate‐buffered saline (PBS) only. Immunohistochemical staining demonstrated that there were more Isolectin B4 and β‐galactosidase double positive cells in the rats transplanted with MDSC‐VEGF transduced cells than the other groups at week 1. Capillary density was significantly higher in the MDSC‐VEGF group than the other groups at week 2; however, there were no significant differences in the biomechanical assessment between the MDSC‐VEGF and MDSC‐nLacZ groups. On the other hand, the MDSC‐sFLT1 group revealed a lower capillary density than the other two groups and the functional ligament healing of the MDSC‐sFLT1 group was significantly decreased compared to the other groups when assessed biomechanically. The findings of the present study suggest that angiogenesis plays a critical role in the healing process of injured MCL.

In vitro cartilage formation using TGF‐β‐immobilized magnetic beads and mesenchymal stem cell‐magnetic bead complexes under magnetic field conditions

We evaluated the efficacy of transforming growth factor (TGF)-beta-immobilized magnetic beads for chondrogenesis in vitro using a mesenchymal stem cell (MSC) delivery system and an external magnetic force (EMF). MSCs isolated from the bone marrow of Sprague Dawley rats were mixed with carboxyl group-combined magnetic beads (Ferri Sphere 100C) coated with anti-rat CD44 mouse monoclonal antibodies. TGF-beta3 (10 and 1 ng/mL) was attached magnetically to such other Ferri Sphere 100C beads via an amide bond formed between a primary amino group on the TGF-beta3 and the carboxyl groups on the surface of the beads. MSC-magnetic bead complexes were centrifuged to form a pellet and cultured in chondrogenic differentiation medium (CDM) supplemented with either 10 or 1 ng/mL TGF-beta-immobilized magnetic beads (10 or 1 ng/mL TGF-beta-immobilized magnetic bead groups) or in CDM supplemented with 1 or 10 ng/mL TGF-beta (1 or 10 ng/mL TGF-beta group). TGF-beta-immobilized magnetic beads were gathered effectively under an EMF. Chondrogenesis was achieved from the MSC-magnetic bead complexes in the presence of 1 ng/mL TGF-beta-immobilized magnetic beads.

Repair of a large osteochondral defect in the knee joint using autologous and artificial bone graft combined with motion preserving distraction arthroplasty: a case report

The biological reconstruction of a large osteochondral defect in the weight-bearing area of the knee joint has long been a challenge to orthopedic surgeons. We present a case of a large posttraumatic defect in the weight-bearing area of knee joint treated with a novel distraction arthroplasty device after reconstruction of the joint surface using combined autologous and artificial bone graft.

Intra-articular angiolipoma of the knee: a case report

We report a case of intra-articular angiolipoma of the knee. This case report describes our experience in excising an intra-articular angiolipoma of the knee joint. Complete resection under arthroscopy was performed in a 30-year-old man. Two years after the surgery, no evidence of recurrence was seen. Intra-articular angiolipomas should be considered in the differential diagnosis of intra-articular masses in adolescents with recurrent hemarthrosis without trauma.