髌骨骨-骨膜原位翻转修复软骨缺损的基础研究及临床应用

目的 探讨治疗髌骨软骨缺损的简便、有效的方法，并分析新生软骨退变的原因。方法 （1）设计动物实验，将家兔附骨骨－骨膜块植入股骨髁间人为形成的缺损处。（2）取人体髌前及胫骨上段骨－骨膜块标本进行组织学对比。（3）选择适合病人7例，用环锯将髌骨软骨病变区全层髌骨与骨膜完整切取，翻转后原位再植。结果 （1）动物实验示骨膜演化为软骨的过程分为间充质细胞增殖分化、软骨细胞形成有新生软骨改造塑形、透明软骨组织成熟三个阶段。（2）人体髌前骨膜生发层未分化间充质细胞分布较密集。（3）要后临床随访5－53个月，平均26．7个,膝关节功能恢复良好。结论 手术操作是否得当对新生软骨的形成影响很大。导致新生软骨退变的主要因素有：（1）未能注射修复的“完整性原则”；（2）骨膜生发层朝向关节腔。     

Biomechanical and histological evaluation of osteochondral transplantation in a rabbit model

BACKGROUND: Biomechanical and histological properties of osteochondral transplantation have not been extensively examined. HYPOTHESIS: Osteochondral grafts have properties similar to native articular cartilage. STUDY DESIGN: Controlled laboratory study. METHODS: A 2.7 mm (diameter) x 4.0 mm (depth) osteochondral defect was created in 17 New Zealand white rabbit knees. An osteochondral graft, harvested from the contralateral knee, was transplanted into the defect. Eight rabbits were sacrificed each at 6 and 8 weeks. RESULTS: The 12-week grafts (1213.6 +/- 309.0 N/mm) had significantly higher stiffness than the 6-week grafts (483.1 +/- 229.1 N/mm; P <.001) and of normal cartilage (774.8 +/- 117.1 N/mm; P <.003). Stiffness of the 6-week grafts was significantly lower than normal cartilage (P <.036). At all time points, full-thickness defects had significantly lower stiffness than normal cartilage (P <.001). Histologically, transplanted grafts scored significantly higher than the full-thickness defects (P <.001). The defects showed inconsistent, fibrocartilage healing. The grafts demonstrated cartilage viability, yet with a persistent cleft between the graft and host. CONCLUSIONS: Osteochondral transplants undergo increased stiffness in the short term, with evidence of structurally intact grafts. Clinical Relevance: Osteochondral transplantation may be a viable treatment option; however, long-term investigation on graft function is necessary.     

Osteochondral autograft transplantation in the porcine knee

BACKGROUND: Knee articular cartilage defects are not an uncommon problem. Because articular cartilage is limited in its ability to heal, these defects are difficult to manage. HYPOTHESIS: Osteochondral autografts will provide less of a cavitary defect and more viable hyaline articular cartilage than will control knees. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral autografts were grossly and microscopically evaluated in the porcine knee and compared with a control at 6 weeks, 3 months, and 6 months. In 18 porcine specimens, a 1-stage surgical procedure was performed to harvest an osteochondral graft from a nonweightbearing articular cartilage surface, and the graft was transplanted into a defect created in the weight-bearing region of the medial femoral condyle. In the opposite control knee, a similar defect was created in the medial femoral condyle; an osteochondral transplant was not performed. Six pigs each were sacrificed at 6 weeks, 3 months, and 6 months. RESULTS: Gross inspection of the control knees showed a cavitary defect. The defect grossly decreased in size with fibrous ingrowth seen on microscopic analysis. An increasing amount of fibrous tissue and fibrocartilage was present at the 3 time periods. Gross inspection of the graft knee showed a healed osteochondral plug with no obvious displacement, cavitary defects, or surrounding necrotic tissue at each time interval. Microscopic analysis revealed the graft knee contained viable hyaline cartilage and healed viable subchondral bone. At all time intervals, 75% to 100% of the hyaline cartilage was viable in all specimens. In 6-month specimens, bridging cartilage at the autograft-host junction was incomplete in 50%, partial in 33%, and complete in 17%. CONCLUSION: Osteochondral autografts in the porcine knee resulted in viable hyaline cartilage for up to 6 months; there was inconsistent bridging hyaline cartilage at the periphery. Grafts appeared to heal into existing subchondral bone without displacement or evidence of necrosis. CLINICAL RELEVANCE: This type of osteochondral transplant can be used as a reliable reconstructive alternative for osteochondral defects.     

Radiographic evaluation of the knee joint after meniscal allograft transplantation. An experimental study in rabbits

Experimental and clinical studies have documented that meniscal allografts show capsular ingrowth in meniscectomized knees. However, it remains to be established whether meniscal allograft transplantation can prevent degenerative changes after total meniscectomy. In this study radiography was used to compare changes in rabbit knees after meniscectomy and after meniscal transplantation. Thirty-two mature female New Zealand rabbits were divided into five groups: group A ( n=6) and group C ( n=6) underwent meniscectomy; group B ( n=7) and group D ( n=6) were subjected to meniscal transplantation immediately after meniscectomy; in group E ( n=7) a delayed meniscus transplantation was performed 6 weeks after meniscectomy. Radiographic changes were evaluated 6 weeks (groups A, B) and 1 year (groups C-E) postoperatively. One year after surgery both meniscectomized and transplanted knees showed significantly more radiographic changes than after 6 weeks. At 1-year follow-up no statistically significant radiographic differences were found between the joints that had undergone meniscectomy and those that were subjected to immediate or delayed meniscal transplantation. Our findings suggest that meniscal allograft transplantation does not prevent degenerative changes in the rabbit knee on a long term.     

Radiographic joint space narrowing and histologic changes in a rabbit meniscectomy model of early knee osteoarthrosis

The purpose of this study was to compare weightbearing radiographs with histologic cartilage evaluation in a rabbit meniscectomy model of the early stage of osteoarthrosis. Fifteen rabbits had a medial meniscectomy performed in one knee and a sham operation in the other knee. Five rabbits each were sacrificed at 13, 25, and 40 weeks after surgery. Radiographic joint space width and histologic cartilage changes of the medial knee compartment were quantified. Five non-operated knees and five knees in which the meniscus had been removed immediately before the evaluations served as control specimens. Overall, the joint space of the peripheral part of the medial knee compartment was narrower in knees operated on for meniscus removal than in sham-operated knees (P < 0.003). In the knees with the meniscus removed, more cartilage changes were seen at the joint surface area of contact on radiographs than in the sham-operated knees (P < 0.0015). Indeed, the area of contact had cartilage changes similar to those in the whole medial compartment. However, there was no correlation between the degree of histologic cartilage change and the corresponding joint space measurements. Joint space width as measured on weightbearing radiographs is reduced after meniscectomy in the rabbit, but it does not reflect the degree of cartilage damage of the loaded joint surfaces in early stages of osteoarthrosis.     

Collagen biosynthesis in rabbit intraarticular patellar tendon transplants

Autogenous patellar tendon grafts were transplanted into the knees of 40 New Zealand White adult rabbits. Grafts were subsequently analyzed for rate of collagen synthesis, collagen content, collagen type, histologic change, and cyanogen bromide cleavage patterns of collagen to closely assess the nature of collagen in tendon grafts up to 2 years from the time of transplantation. Tendon grafts were placed in rabbit knees as free fragments or were attached to synovium. These studies show that tendon grafts, even without vascularization or stress, remain viable after intraarticular transfer. Vascularization produces a trend toward increased collagen synthesis, but statistical analysis suggests that control levels of collagen synthesis continue after tendon transfers into rabbit knees. Cyanogen bromide cleavage peptides showed appropriate collagen formed by unstressed autogenous tendon transplants removed from rabbit knees up to 2 years from transplantation. All tendon grafts degenerated initially, but began to form histologically healthy looking connective tissue by 18 to 24 weeks after transplantation. Overall, the results are encouraging with regard to the fate of intraarticular tendon grafts.     

Autologous chondrocyte transplantation. Biomechanics and long-term durability.

We evaluated the durability of autologous chondrocyte transplantation grafts in 61 patients treated for isolated cartilage defects on the femoral condyle or the patella and followed up for a mean of 7.4 years (range, 5 to 11). Durability was determined by comparing the clinical status at the long-term follow-up with that found 2 years after the transplantation. After 2 years, 50 of the 61 patients had good or excellent clinical results, and 51 of 61 had good or excellent results at 5 to 11 years later. Grafted areas from 11 of the patients were evaluated with an electromechanical indentation probe during a second-look arthroscopy procedure (mean follow-up, 54.3 months; range, 33 to 84); stiffness measurements were 90% or more of those of normal cartilage in eight patients. Eight of twelve 2-mm biopsy samples taken from these patients showed hyaline characteristics with safranin O staining and a homogeneous appearance in polarized light. Three fibrous and eight hyaline biopsy specimens stained positive to aggrecan and to cartilage oligomeric matrix protein. Hyaline-like specimens stained positive for type II collagen, and fibrous, for type I collagen. Autologous chondrocyte transplantation for the treatment of articular cartilage injuries has a durable outcome for as long as 11 years.     

髌骨倾斜导致髌骨软骨软化实验研究

为了研究髌骨倾斜是否为髌骨软骨软化（ＣＰ）的病因,髌骨软骨软化的发生与何种异常应力有关,选用２４只雌性新西兰兔,随机分４组,每组６只。右膝为实验侧,将髌外侧支持带紧缩造成髌骨外侧倾斜,左膝实施假手术为对照侧,定期处死动物,分别进行髌骨倾斜角Ｘ线测量、髌骨软骨面的接触压力测量、软骨组织切片观察以及软骨组织Ｍａｎｋｉｎ评分。结果显示：实验侧髌骨倾斜角明显大于对照侧。术后６周至１２周时,实验侧髌骨内侧软骨面接触压力明显较对照侧减低（ｐ＜０．０５）。光镜下,术后６周时髌骨内侧面软骨中层与深层轻度变性,１２周至１８周时软骨明显变性,软骨细胞坏死或Ｃｌｏｎｅ状增生,中层与深层软骨基质较多纵行裂隙以及片状苏木素深染的纤维网,表面溃疡形成,ＳａｆｒａｎｉｎＯ染色提示蛋白多糖严重丢失。软骨组织Ｍａｎｋｉｎ评分,实验侧髌骨内侧面软骨得分高于髌骨外侧面软骨（ｐ＜０．０５）,说明髌骨内侧面软骨退变较外侧面明显。结论：髌骨倾斜造成髌骨内侧面应力减低导致髌骨软骨软化。     

Treatment of deep cartilage defects of the patella with periosteal transplantation

Twenty-six consecutive patients (19 men and 7 women) with a mean age of 31.5 years (range 19–52 years) who suffered from an isolated full-thickness cartilage defect of the patella (area ranged from 0.75 to 20.0 cm²) and disabling knee pain were treated with autologous periosteal transplantation (without any chondrocytes). The duration of symptoms was 59 months (range 11–144 months). During the first 5 postoperative days all patients were treated with continuous passive motion (CPM). This was followed by active motion, slowly progressive strength training, and slowly progressive weight-bearing. After a mean follow-up of 42 months (range 24–76 months), 17 patients (65%) were graded as excellent (were painfree), 8 patients (31%) as good (had pain with strenous knee-loading activities), and 1 patient as poor (had pain at rest). Twenty-two patients (85%) had returned to their previous occupation. Twelve patients (46%) had resumed sports or recreational activities at their former level. Repeated magnetic resonance imaging (MRI) investigations showed progressive, and finally complete, filling of the articular defects. Biopsies taken in five randomly selected cases showed hyaline-like cartilage. Patients with full-thickness cartilage defects of the patella and disabling knee pain can be treated with autologous periosteal transplantation (without any chondrocytes), followed by CPM, and slowly progressive strength training and weight-bearing. We believe this is a good method to accomplish regeneration of articular cartilage and satisfactory clinical results. Received: 25 March 1998 Accepted: 14 April 1998     

髌骨关节软骨体视学研究

采用体视学的方法，测量家兔髌骨软骨负重区的软骨体视学变化，包括软骨细胞数、体密度、面密度、比表面等各项指标。利用图象分析技术进行关节定量化的形态学分析，对于研究关节软骨损伤，修复过程及软骨疾病的发病原理均有重要意义。实验结果表明，透明软骨与钙化软骨具有显著差别。透明软骨除单个细胞面积数值较小外，其体密度、面密度、数密度和比表面均较钙化软骨的数值为高。透明软骨细胞核的体密度和面密度亦高于钙化软骨细胞核。这些数据对研究关节软骨功能和病理变化有重要意义。     

A cadaveric analysis of contact stress restoration after osteochondral transplantation of a cylindrical cartilage defect

Osteochondral transplantation is a successful treatment for full-thickness cartilage defects, which without treatment would lead to early osteoarthritis. Restoration of surface congruency and stability of the reconstruction may be jeopardized by early mobilization. To investigate the biomechanical effectiveness of osteochondral transplantation, we performed a standardized osteochondral transplantation in eight intact human cadaver knees, using three cylindrical plugs on a full-thickness cartilage defect, bottomed on one condyle, unbottomed on the contralateral condyle. Surface pressure measurements with Tekscan pressure transducers were performed after five conditions. In the presence of a defect the border contact pressure of the articular cartilage defect significantly increased to 192% as compared to the initially intact joint surface. This was partially restored with osteochondral transplantation (mosaicplasty), as the rim stress subsequently decreased to 135% of the preoperative value. Following weight bearing motion two out of eight unbottomed mosaicplasties showed subsidence of the plugs according to Tekscan measurements. This study demonstrates that a three-plug mosaicplasty is effective in restoring the increased border contact pressure of a cartilage defect, which may postpone the development of early osteoarthritis. Unbottomed mosaicplasties may be more susceptible for subsidence below flush level after (unintended) weight bearing motion.     

组织工程重建兔颞下颌关节盘软骨

目的 应用组织工程学方法重建颞下颌关节盘软骨。方法 分离6只日本大耳白兔髁状突软骨细胞。进行细胞的微载体大规模扩增,将扩增后的软骨细胞接种于组织引导再生胶原膜,体外适当培养后植入4只同种成年兔皮下,植入后12周,对所获组织进行组织形态学观察。结果 髁状[突软骨细胞在胶原膜内生长良好,植入动物体内12周后可形成乳白色类软骨样组织,其表面光滑,有弹性。甲苯胺蓝染色,细胞周围基质呈异染性。结论 应用胶原膜结合软骨细胞共同培养,可形成软骨样组织,该方法将有可能成为软骨缺损及关节盘破损修复的有途径。     

Effects of small incongruities in a sheep model of osteochondral autografting

BACKGROUND: Exact reconstruction of an osteochondral defect by autogenous transplantation (mosaicplasty) is difficult given the variation in joint surface contour. Clinical and experimental studies do not show the extent to which incongruity can be tolerated in autografting. HYPOTHESIS: Grafted articular cartilage will hypertrophy to correct the incongruity created by recession of the transplanted surface. STUDY DESIGN: Controlled laboratory study. METHODS: To test the response of grafts to incongruities, osteochondral autografts were transplanted from the trochlea to the femoral condyle in adult male sheep stifle joints. In groups of 6 animals, graft surfaces were placed flush, countersunk 1 mm or countersunk 2 mm, then histologically analyzed 6 weeks after surgery. Cartilage thickness, condition of the articular surfaces, and preservation of hyaline characteristics were the primary features compared. RESULTS: Bony union, vascularization, and new bone formation were present in all grafts. Cartilage-to-cartilage healing did not occur. In flush specimens, cartilage changed minimally in thickness and histologic architecture. The specimens countersunk 1 mm demonstrated significant cartilage thickening (54.7% increase, P <.05). Chondrocyte hyperplasia, tidemark advancement, and vascular invasion occurred at the chondroosseous junction, and the surface remained smooth. Cartilage necrosis and fibrous overgrowth were observed in all grafts countersunk 2 mm. CONCLUSIONS: Minimally countersunk autografts possess a capacity for remodeling that can correct initial incongruities while preserving hyaline characteristics. Grafts placed deeper do not restore the contour or composition of the original articular surface. CLINICAL RELEVANCE: If preservation of normal hyaline cartilage is the objective, thin grafted articular cartilage can remodel, but the tolerance for incongruity is limited and probably less than that reported for an intra-articular fracture.     

异种异体和同种异体半月板移植术后兔半月板和关节软骨中Ⅰ、Ⅱ、Ⅲ、Ⅹ型胶原表达和免疫排斥研究

目的 :研究同种异体半月板移植和异种异体半月板移植后 ,移植半月板和关节软骨中的Ⅰ、Ⅱ、Ⅲ、Ⅹ型胶原表达和免疫排斥反应发生的情况。方法 :切除 30只成年新西兰白兔的内侧半月板造成半月板缺失的动物模型。A组进行同种异体内侧半月板移植。B组取猪半月板组织修剪成同兔内侧半月板形态和尺寸相同的异种异体半月板植入物 ,进行兔内侧半月板的异种异体移植。分别在术后第 6周、12周、2 4周取实验动物的半月板、关节软骨进行Ⅰ、Ⅱ、Ⅲ、Ⅹ型胶原的单克隆抗体的免疫组织化学染色 ,并取外周血进行补体依赖性微量淋巴细胞毒实验 (CDMT) ,用放射免疫法检测血清中IL - 2和IL - 6的含量 ,了解是否发生免疫排斥反应。结果 :同种异体半月板移植后 ,关节软骨和移植半月板的情况良好 ,但术后第 2 4周 ,异种异体移植物部分被吸收 ,关节软骨出现损伤。两组中各时段移植半月板中的Ⅰ、Ⅱ和Ⅲ型胶原的表达情况无明显差异 ,术后第 12周 ,两组关节软骨中Ⅰ、Ⅱ和Ⅲ型胶原的表达情况相似 ,但术后第 2 4周 ,异种异体半月板组的关节软骨开始有异常Ⅹ型胶原表达。同种异体和异种异体半月板移植组均未发现致命的免疫排斥反应发生。结论 :用猪的半月板组织塑形后移植替代兔内侧半月板组织 ,半年后移植物被溶解吸收 ,同种异体?     

Superior results with continuous passive motion compared to active motion after periosteal transplantation A retrospective study of human patella cartilage defect treatment

Fifty-seven consecutive patients (33 men and 24 women), with a mean age of 32 years (range 16–53 years), who suffered from an isolated full-thickness cartilage defect of the patella and disabling knee pain of long duration, were treated by autologous periosteal transplantation to the cartilage defect. The first 38 consecutive patients (group A) were postoperatively treated with continuous passive motion (CPM), and the next 19 consecutive patients (group B) were treated with active motion for the first 5 days postoperatively. In both groups, the initial regimens were followed by active motion, slowly progressive strength training, and slowly progressive weight bearing. In group A, after a mean follow-up of 51 months (range 33–92 months), 29 patients (76%) were graded as excellent or good, 7 patients (19%) were graded as fair, and 2 patients (5%) were graded as poor. In group B, after a mean follow-up of 21 months (range 14–28 months), 10 patients (53%) were graded as excellent or good, 6 patients (32%) were graded as fair, and 3 patients (15%) were graded as poor. Altogether, nine of the fair or poor cases (50%) were diagnosed with chondromalacia of the patella. Our results, after performing autologous periosteal transplantation in patients with full-thickness cartilage defects of the patella and disabling knee pain, are good if CPM is used postoperatively. The clinical results using active motion postoperatively are not acceptable, especially not in patients with chondromalacia of the patella. Received: 24 November 1998 Accepted: 30 January 1999     

大块脱钙异体骨关节移植修复兔节段性骨关节缺损

目的：探讨脱钙异体骨关节移植修复节段性骨关节缺损的作用．方法：在兔桡骨近段造成２０ｍｍ长骨关节缺损，分别移植脱钙异体骨关节和自体骨关节及不移植，通过Ｘ线照片、生物力学试验和组织学检查作对照观察．结果：脱钙异体骨关节移植后通过新生骨和软组织爬行替代生成新的骨关节，具有正常骨关节形态特征，抗扭转强度接近正常；自体骨关节移植后的愈合过程与骨折愈合过程基本相似；不移植组至术后２４周仍未见新的骨关节形成．结论：脱钙异体骨关节具有低抗原性、高骨诱导能力和诱导关节软骨再生的特点，可作为临床修复节段性骨关节缺损的移植材料．     

Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo

Purpose

The combination of chondrogenic factors might be necessary to adequately stimulate articular cartilage repair. In previous studies, enhanced repair was observed following transplantation of chondrocytes overexpressing human insulin-like growth factor I (IGF-I) or fibroblast growth factor 2 (FGF-2). Here, the hypothesis that co-overexpression of IGF-I and FGF-2 by transplanted articular chondrocytes enhances the early repair of cartilage defects in vivo and protects the neighbouring cartilage from degeneration was tested.

Methods

Lapine articular chondrocytes were transfected with expression plasmid vectors containing the cDNA for the Escherichia coli lacZ gene or co-transfected with the IGF-I and FGF-2 gene, encapsulated in alginate and transplanted into osteochondral defects in the knee joints of rabbits in vivo.

Results

After 3 weeks, co-overexpression of IGF-I/FGF-2 improved the macroscopic aspect of defects without affecting the synovial membrane. Immunoreactivity to type-I collagen, an indicator of fibrocartilage, was significantly lower in defects receiving IGF-I/FGF-2 implants. Importantly, combined IGF-I/FGF-2 overexpression significantly improved the histological repair score. Most remarkably, such enhanced cartilage repair was correlated with a 2.1-fold higher proteoglycan content of the repair tissue. Finally, there were less degenerative changes in the cartilage adjacent to the defects treated with IGF-I/FGF-2 implants.

Conclusion

The data demonstrate that combined gene delivery of therapeutic growth factors to cartilage defects may have value to promote cartilage repair. The results also suggest a protective effect of IGF-I/FGF-2 co-overexpression on the neighbouring articular cartilage. These findings support the concept of implementing gene transfer strategies for articular cartilage repair in a clinical setting.     

Cartilage repair: generations of autologous chondrocyte transplantation

Articular cartilage in adults has a limited capacity for self-repair after a substantial injury. Surgical therapeutic efforts to treat cartilage defects have focused on delivering new cells capable of chondrogenesis into the lesions. Autologous chondrocyte transplantation (ACT) is an advanced cell-based orthobiologic technology used for the treatment of chondral defects of the knee that has been in clinical use since 1987 and has been performed on 12,000 patients internationally. With ACT, good to excellent clinical results are seen in isolated post-traumatic lesions of the knee joint in the younger patient, with the formation of hyaline or hyaline-like repair tissue. In the classic ACT technique, chondrocytes are isolated from small slices of cartilage harvested arthroscopically from a minor weight-bearing area of the injured knee. The extracellular matrix is removed by enzymatic digestion, and the cells are then expanded in monolayer culture. Once a sufficient number of cells has been obtained, the chondrocytes are implanted into the cartilage defect, using a periosteal patch over the defect as a method of cell containment. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. Further improvements in tissue engineering have contributed to the next generation of ACT techniques, where cells are combined with resorbable biomaterials, as in matrix-associated autologous chondrocyte transplantation (MACT). These biomaterials secure the cells in the defect area and enhance their proliferation and differentiation.     

不同细胞移植修复兔全层关节软骨缺损的比较研究

目的 :比较软骨细胞、骨髓基质细胞及成纤维细胞对全层关节软骨缺损的修复作用。材料和方法 :取幼兔的软骨细胞、骨髓基质细胞及成纤维细胞 ,共 3种有生成软骨潜力的细胞进行体外分离培养 ;以聚乳酸 (PLA)为载体 ,将培养的原代细胞植入PLA支架上 ,形成细胞 -PLA复合物。于 2 8只成年新西兰大白兔的股骨滑车关节面上造成直径 4 5mm、深 3 0mm的全层关节软骨缺损 ,将 3种细胞 -PLA复合物分别植入关节软骨缺损处。植入细胞 -PLA复合物为实验组 ,单纯植入PLA支架为对照组。术后 6周、12周观察缺损修复情况及新生组织类型。结果 :软骨细胞移植组为软骨样组织修复 ,分界明显 ,甲苯胺兰及Ⅱ型胶原染色阳性 ;软骨下骨部分重建 ;细胞排列紊乱。骨髓基质细胞移植组为软骨样组织修复 ,分界不明显 ,甲苯胺兰及Ⅱ型胶原染色阳性 ;软骨下骨重建良好 ,软骨下潮线恢复 ;细胞排列趋于正常。成纤维细胞移植组为纤维组织修复 ,甲苯胺兰及Ⅱ型胶原染色阴性 ;软骨下潮线消失。对照组为纤维组织修复。结论 :软骨细胞、骨髓基质细胞移植修复软骨缺损明显优于成纤维细胞及对照组。骨髓基质细胞与软骨细胞移植组的修复结果无统计学差异 ,但骨髓基质细胞修复组织的细胞排列有序 ,软骨下骨重建良好 ,与周围组织融合密切 ,更接近正?     

骨性关节炎的联合基因治疗研究

目的:探讨白细胞介素1受体拮抗蛋白(IL-1Ra)及白细胞介素10双基因转染在关节中的表达及在骨性关节炎(OA)治疗中的作用。方法:构建PLXRN-IL-1Ra、PLXRN-IL-10逆转录病毒载体,体外转染同种异体原代滑膜细胞,将转染了外源基因的滑膜细胞注射入兔骨性关节炎膝关节腔。外源基因注射后第7天,用PBS灌洗兔膝关节,ELISA分析转基因表达;外源基因注射后第14天处死动物,ELISA及免疫组化分析转基因表达,软骨滑膜常规石蜡切片观察病理改变,并进行软骨组织学评分。结果:外源基因转移后14天表达尚很稳定,治疗基因在受体关节的滑膜衬里部位表达。只接受人IL-1Ra基因治疗的兔膝关节软骨损坏明显减轻;单纯人IL-10基因治疗膝关节也有一定效果;两种基因同时导入时,有非常明显的抑制软骨破坏和软骨基质降解的作用。结论:以逆转录病毒为载体将IL-1Ra、IL-10同时转移入早期骨关节炎关节内,有稳定的外源基因表达,且联合基因治疗效果明显优于单独转移入其中任何一种基因,提示靶向于多种炎性因素的治疗更为有效。