Ripamonti U, Bosch C, van den Heever B, Duneas N, Melsen B, Ebner R
Bone Research Laboratory, Medical Research Council/University of the Witwatersrand, Johannesburg, South Africa.
J Bone Miner Res. 1996 Jul;11(7):938-45. doi: 10.1002/jbmr.5650110710.
The therapeutic utility of a single application of recombinant human transforming growth factor-beta (hTGF-beta) has not been previously tested in large osseous wounds in primates. Sixteen calvarial defects, 25 mm in diameter, were prepared in four adult male baboons (Papio ursinus). In each animal, three defects were treated with increasing doses of hTGF-beta 1 in conjunction with baboon insoluble collagenous bone matrix as carrier (5, 30, and 100 micrograms of hTGF-beta 1/g of matrix). The fourth defect was implanted with collagenous matrix without hTGF-beta 1 as control. Serial undecalcified sections were prepared from the specimens harvested on day 30. Islands of cartilage and endochondral osteogenesis were found in hTGF-beta 1-treated defects, irrespective of the doses used. Histomorphometry of the defect site showed no significant differences between control and hTGF-beta 1-treated specimens with regard to bone and osteoid volumes. However, analysis of the regenerated tissue in proximity to the defect margins only showed that, on average, greater amounts of bone formed in specimens that were treated with 5 and 30 micrograms of hTGF-beta 1 when compared with controls. This suggests a possible effect on osteoblastic cells originating from the periosteal and endosteal spaces of the severed calvaria. Overall, however, this difference has no therapeutic implications for the healing of large cranial wounds in primates. The present findings indicate that a single application of hTGF-beta 1, in conjunction with collagenous matrix, results in limited chondro-osteogenesis in defects of membranous bone of adult baboons.
重组人转化生长因子-β(hTGF-β)单次应用在灵长类动物大骨缺损中的治疗效用此前尚未得到测试。在四只成年雄性狒狒(山魈)身上制备了16个直径为25毫米的颅骨缺损。在每只动物身上,三个缺损用递增剂量的hTGF-β1联合狒狒不溶性胶原骨基质作为载体进行治疗(5、30和100微克hTGF-β1/克基质)。第四个缺损植入不含hTGF-β1的胶原基质作为对照。对第30天收获的标本制备系列不脱钙切片。在hTGF-β1治疗的缺损处发现了软骨岛和软骨内成骨,无论使用何种剂量。缺损部位的组织形态计量学显示,对照和hTGF-β1治疗的标本在骨和类骨质体积方面无显著差异。然而,仅对缺损边缘附近的再生组织分析表明,与对照相比,平均而言,用5和30微克hTGF-β1治疗的标本中形成的骨量更多。这表明对源自切断颅骨骨膜和骨内膜间隙的成骨细胞可能有影响。然而,总体而言,这种差异对灵长类动物大颅骨伤口的愈合没有治疗意义。目前的研究结果表明,hTGF-β1与胶原基质联合单次应用在成年狒狒膜性骨缺损中导致有限的软骨内成骨。