Stem cells as vehicles for orthopedic gene therapy.

Adult stem cells reside in adult tissues and serve as the source for their specialized cells. In response to specific factors and signals, adult stem cells can differentiate and give rise to functional tissue specialized cells. Adult mesenchymal stem cells (MSCs) have the potential to differentiate into various mesenchymal lineages such as muscle, bone, cartilage, fat, tendon and ligaments. Adult MSCs can be relatively easily isolated from different tissues such as bone marrow, fat and muscle. Adult MSCs are also easy to manipulate and expand in vitro. It is these properties of adult MSCs that have made them the focus of cell-mediated gene therapy for skeletal tissue regeneration. Adult MSCs engineered to express various factors not only deliver them in vivo, but also respond to these factors and differentiate into skeletal specialized cells. This allows them to actively participate in the tissue regeneration process. In this review, we examine the recent achievements and developments in stem-cell-based gene therapy approaches and their applications to bone, cartilage, tendon and ligament tissues that are the current focus of orthopedic medicine.

[Immediate posterior stabilization of pelvic fractures using threaded compression rods].

Operative management of pelvic ring disruptions remains a challenge for the orthopedist. Surgical stabilization of an unstable pelvic ring not only involves urgent control of shock, but also protects soft tissues and enables the patient to ambulate earlier and to be comfortable when resting. Appropriate management of pelvic ring injuries requires understanding the anatomy and biomechanics of the pelvis and the mechanism of injury. The choice of posterior stabilization depends on the type of fracture. In this study we evaluated posterior tansiliac fixation using threaded compression rods (sacral bars), 1 of the techniques for treating pelvic instability with disruption of the posterior osseous - ligamentous complex. We used this method during 1987 - 1991 on 17 multitrauma patients with unstable pelvic injuries. We also conducted a long-term follow-up of more than 2 years. The 2 type C3 patients required revision of the posterior fixation, due to loss of stability and recurrence of dislocation of the sacroiliac joint. This seems to support the view that posterior sacral bar fixation is not suitable for bilateral rotational and vertical instability, and that it should be limited to certain posterior injury patterns, including lateral compression injuries and unilateral vertical instability when the contralateral hemipelvis is stable. It is important therefore, that the trauma surgeon be familiar with more than 1 technique of stabilization. Our study indicated that fixation with sacral bars is still an easy, safe and useful method for treating posterior pelvic instability, even though anatomical reduction of the sacroiliac joint is difficult. It should be one of the techniques with which the orthopedic trauma surgeon is acquainted and is ready to use when necessary.

Osteoarthritis, the hazard of living longer: arthroscopy vs. conservative treatment.

The lengthening of the average life span has led to an increase in degenerative diseases, among them osteoarthritis. Arthroscopy, which has been used extensively to decrease pain and inflammation and increase the range of motion, has recently been challenged as the treatment of choice. Several studies have found that joint lavage, which is a less costly procedure, provides better solutions to joint disorders. In Israel, where resources for health care are limited, physicians must also be guided by cost-benefit and cost-effectiveness. Since there is limited benefit to be gained from arthroscopy in cases where there is no mechanical damage to the knee, we suggest that nonsurgical, conservative methods be employed in treating the majority of cases of osteoarthritis.

Crush injuries of the foot with compartment syndrome: immediate one-stage management.

Severe crush injuries with compartment syndrome were treated in five patients by an immediate one-stage procedure. This procedure included the assessment of skin flap viability with accurate debridement of devascularized tissues. It was performed according to the split-thickness skin excision technique. Compartment pressures were measured and the fasciotomies were performed through open wounds or separate medial and lateral incisions. The medial incision was extended to release the tarsal tunnel. Fractures were reduced and internally fixed and exposed bones were covered with locally transposed muscles. Skin grafts, taken earlier for the skin viability assessment, were meshed and applied to replace skin loss. All wounds and fractures healed uneventfully with no major functional loss. In multiple trauma, the physician should maintain a high index of suspicion for early diagnosis and treatment of severe foot injuries. Early treatment leads to more desirable results, shorter hospitalization, and faster rehabilitation.

Production of C5a antagonist by synovial and peritoneal tissue fibroblasts.

Fibroblasts grown from synovial and peritoneal tissues release into the medium an inhibitor of neutrophil chemotaxis. The inhibitor resembles the antagonist previously described in synovial and peritoneal fluids. It is a heat stable (56 degrees C) protein of MW approximately 40 kDa that counteracts the chemotactic activity of zymosan-activated serum or purified C5a but not the peptide chemoattractant F-met-leu-phe. No chemotactic inhibitor was detected in media from skin fibroblast cultures or in formal human sera. It is suggested that the inhibitor is produced locally by synovial and peritoneal fibroblasts and that it might play a role in the regulation of inflammation at sites lined with mesothelium.

The effect of non-inflamed synovial fluid on neutrophil function in vitro.

In neutrophils preincubated with non-inflamed synovial fluid, opsonized zymosan-induced O2- production was increased by 232.7 +/- 19.1% and degranulation induced by zymosan or phorbol myristate acetate was increased by 152.8 +/- 21.8% and 217.4 +/- 26.3 respectively. Unstimulated neutrophils were not directly activated by the fluid, nor did it affect their chemotactic response. The activity was not abolished by heat (56 degrees C, 30 min, or 100 degrees C, 3 min) or by treatment with trypsin or hyaluronidase. The activity was not present in the serum albumin-bound lipid extract of the synovial fluid. Thus, this activity may represent a heat- and trypsin-resistant factor which is neither a complement component nor hyaluronic acid. It is proposed that this synovial fluid factor plays a role in increasing the neutrophil killing potential during the inflammatory process.