Alsberg Eben, Anderson Kenneth W, Albeiruti Amru, Rowley Jon A, Mooney David J
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12025-30. doi: 10.1073/pnas.192291499. Epub 2002 Sep 6.
Regenerating or engineering new tissues and organs may one day allow routine replacement of lost or failing tissues and organs. However, these engineered tissues must not only grow to fill a defect and integrate with the host tissue, but often they must also grow in concert with the changing needs of the body over time. We hypothesized that tissues capable of growing with time could be engineered by supplying growth stimulus signals to cells from the biomaterial used for cell transplantation. In this study, chondrocytes and osteoblasts were cotransplanted on hydrogels modified with an RGD-containing peptide sequence to promote cell multiplication. New bone tissue was formed that grew in mass and cellularity by endochondral ossification in a manner similar to normal long-bone growth. Transplanted cells organized into structures that morphologically and functionally resembled growth plates. These engineered tissues could find utility in treating diseases and injuries of the growth plate, testing the effect of experimental drugs on growth-plate function and development, and investigating the biology of long-bone growth. Furthermore, this concept of promoting the growth of engineered tissues could find great utility in engineering numerous tissue types by way of the transplantation of a small number of precursor cells.
再生或构建新的组织和器官或许有朝一日能实现对受损或功能衰竭的组织和器官进行常规替换。然而,这些构建的组织不仅要生长以填补缺损并与宿主组织整合,而且通常还必须随着时间的推移与身体不断变化的需求协同生长。我们推测,通过向用于细胞移植的生物材料中的细胞提供生长刺激信号,能够构建出随时间生长的组织。在本研究中,将软骨细胞和成骨细胞共同移植到用含RGD肽序列修饰的水凝胶上,以促进细胞增殖。形成了新的骨组织,其通过软骨内成骨在质量和细胞数量上生长,方式类似于正常长骨生长。移植的细胞组织成在形态和功能上类似于生长板的结构。这些构建的组织可用于治疗生长板疾病和损伤、测试实验药物对生长板功能和发育的影响以及研究长骨生长生物学。此外,通过移植少量前体细胞来促进构建组织生长的这一概念,在构建多种组织类型方面可能具有很大的实用价值。