Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r)

https://www.cell.com/cell/pdf/S0092-8674(05)80085-6.pdf

Role of Insulin-like Growth Factors in Embryonic and Postnatal Growth

https://www.oarsijournal.com/article/S1063-4584(02)90801-0/pdf

Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects.

Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering : a review

Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update

Background Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. Methods The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. Results Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and s...

Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation

Autologous cultured chondrocyte transplantation was introduced in Sweden in 1987 for the treatment of large (1.5-12.0 cm2) full thickness chondral defects of the knee. The clinical, arthroscopic, and histologic results from the first 101 patients treated using this technique are reported in this study. Patients were assessed retrospectively using three types of endpoints: patient and physician derived clinical rating scales (five validated and two new); arthroscopic assessment of cartilage fill, integration, and surface hardness; and standard histochemical techniques. Ninety-four patients with 2- to 9-years followup were evaluable. Good to excellent clinical results were seen in individual groups as follows: isolated femoral condyle (92%), multiple lesions (67%), osteochondritis dissecans (89%), patella (65%), and femoral condyle with anterior cruciate ligament repair (75%). Arthroscopic findings in 53 evaluated patients showed good repair tissue fill, good adherence to underlying bone, seamless integration with adjacent cartilage, and hardness close to that of the adjacent tissue. Hypertrophic response of the periosteum or graft or both was identified in 26 arthroscopies; seven were symptomatic and resolved after arthroscopic trimming. Graft failure occurred in seven (four of the first 23 and three of the next 78) patients. Histologic analysis of 37 biopsy specimens showed a correlation between hyalinelike tissue (hyaline matrix staining positive for Type II collagen and lacking a fibrous component) and good to excellent clinical results. The good clinical outcomes of autologous chondrocyte transplantation in this study are encouraging, and clinical trials are being done to assess the outcomes versus traditional fibrocartilage repair techniques.

Two- to 9-year outcome after autologous chondrocyte transplantation of the knee.

Adult New Zealand rabbits were used to transplant autologously harvested and in vitro cultured chondrocytes into patellar chondral lesions that had been made previously and were 3 mm in diameter, extending down to the calcified zone. Healing of the defects was assessed by gross examination, light microscope, and histological-histochemical scoring at 8, 12, and 52 weeks. Chondrocyte transplantation significantly increased the amount of newly formed repair tissue compared to that found in control knees in which the lesion was solely covered by a periosteal flap. In another experiment, carbon fiber pads seeded with chondrocytes were used as scaffolds, and repair significantly increased at both 12 and 52 weeks compared to knees in which scaffolds without chondrocytes were implanted. The histologic quality scores of the repair tissue were significantly better in all knees in which defects were treated with chondrocytes compared to knees treated with periosteum alone and better at 52 weeks compared to knees in which defects were treated with carbon scaffolds seeded with chondrocytes. The repair tissue, however, tended to incomplete the bonding to adjacent cartilage. This study shows that isolated autologous articular chondrocytes that have been expanded for 2 weeks in vitro can stimulate the healing phase of chondral lesions. A gradual maturation of the hyalinelike repair with a more pronounced columnarization was noted as late as 1 year after surgery.

Rabbit articular cartilage defects treated with autologous cultured chondrocytes.

OBJECTIVE — Chronic diabetic foot ulcers are a source of major concern for both patients and health care systems. The aim of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) in the management of chronic diabetic foot ulcers. RESEARCH DESIGN AND METHODS — The Hyperbaric Oxygen Therapy in Diabetics with Chronic Foot Ulcers (HODFU) study was a randomized, single-center, double-blinded, placebo-controlled clinical trial. The outcomes for the group receiving HBOT were compared with those of the group receiving treatment with hyperbaric air. Treatments were given in a multi-place hyperbaric chamber for 85-min daily (session duration 95 min), five days a week for eight weeks (40 treatment sessions). The study was performed in an ambulatory setting. RESULTS — Ninety-four patients with Wagner grade 2, 3, or 4 ulcers, which had been present for 3 months, were studied. In the intention-to-treat analysis, complete healing of the index ulcer was achieved in 37 patients at 1-year of follow-up: 25/48 (52%) in the HBOT group and 12/42 (29%) in the placebo group (P 0.03). In a sub-analysis of those patients completing 35 HBOT sessions, healing of the index ulcer occurred in 23/38 (61%) in the HBOT group and 10/37 (27%) in the placebo group (P 0.009). The frequency of adverse events was low. CONCLUSIONS — The HODFU study showed that adjunctive treatment with HBOT facilitates healing of chronic foot ulcers in selected patients with diabetes. Diabetes Care 33:998–1003, 2010

/pdf/hyperbaric-oxygen-therapy-facilitates-healing-of-chronic-8thgq1et3u.pdf

Hyperbaric Oxygen Therapy Facilitates Healing of Chronic Foot Ulcers in Patients With Diabetes

To study the effect of locally infused growth hormone (GH) or insulin-like growth factor I(IGF-I) on slowly cycling cells in the germinal cell layer of the tibial growth plate, osmotic minipumps delivering 143 microCi of [3H]thymidine per day were implanted sc into hypophysectomized rats, and GH (1 microgram) or IGF-I (10 micrograms) was injected daily through a cannula implanted in the proximal tibia The opposite leg served as a control After 12 days of treatment, the osmotic minipumps were removed, and three rats in each group were given GH (20 micrograms/day, sc) for an additional 14 days to chase the labeled cells out of the proliferative layers Labeled cells remained in the germinal layer, in the perichondrial ring, and on the surface of the articular cartilage close to the epiphyseal plate GH administered together with labeled thymidine significantly increased the number of labeled cells in the germinal cell layer compared to that in the control leg (ratio = 195 +/- 013), whereas IGF-I showed no stimulatory effect (ratio = 096 +/- 004) Therefore GH but not IGF-I stimulates the multiplication of the slowly cycling (label-retaining) cells in the germinal layer of the epiphyseal plate IGF-I acts only on the proliferation of the resulting chondrocytes

Anders Nilsson

Papers

Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation

Two- to 9-year outcome after autologous chondrocyte transplantation of the knee.

Rabbit articular cartilage defects treated with autologous cultured chondrocytes.

Hyperbaric Oxygen Therapy Facilitates Healing of Chronic Foot Ulcers in Patients With Diabetes

Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate.