McCarty Rosa C, Gronthos Stan, Zannettino Andrew C, Foster Bruce K, Xian Cory J
Department of Orthopaedic Surgery, Women's & Children's Hospital, Adelaide, Australia.
J Cell Physiol. 2009 May;219(2):324-33. doi: 10.1002/jcp.21670.
Since discovery, significant interest has been generated in the potential application of mesenchymal stem cells or multipotential stromal cells (MSC) for tissue regeneration and repair, due to their proliferative and multipotential capabilities. Although the sheep is often used as a large animal model for translating potential therapies for musculoskeletal injury and repair, the characteristics of MSC from ovine bone marrow have been inadequately described. Histological and gene expression studies have previously shown that ovine MSC share similar properties with human and rodents MSC, including their capacity for clonogenic growth and multiple stromal lineage differentiation. In the present study, ovine bone marrow derived MSCs positively express cell surface markers associated with MSC such as CD29, CD44 and CD166, and lacked expression of CD14, CD31 and CD45. Under serum-deprived conditions, proliferation of MSC occurred in response to EGF, PDGF, FGF-2, IGF-1 and most significantly TGF-alpha. While subcutaneous transplantation of ovine MSC in association with a ceramic HA/TCP carrier into immunocomprimised mice resulted in ectopic osteogenesis, adipogenesis and haematopoietic-support activity, transplantation of these cells within a gelatin sponge displayed partial chondrogenesis. The comprehensive characterisation of ovine MSC described herein provides important information for future translational studies involving ovine MSC.
自发现以来,间充质干细胞或多能基质细胞(MSC)因其增殖和多能能力,在组织再生与修复的潜在应用方面引发了极大关注。尽管绵羊常被用作大型动物模型来转化肌肉骨骼损伤与修复的潜在疗法,但对绵羊骨髓来源的MSC特性描述尚不充分。组织学和基因表达研究先前已表明,绵羊MSC与人类及啮齿动物的MSC具有相似特性,包括其克隆生长能力和多谱系间充质分化能力。在本研究中,绵羊骨髓来源的MSC阳性表达与MSC相关的细胞表面标志物,如CD29、CD44和CD166,且不表达CD14、CD31和CD45。在血清饥饿条件下,MSC的增殖发生于对表皮生长因子(EGF)、血小板衍生生长因子(PDGF)、成纤维细胞生长因子-2(FGF-2)、胰岛素样生长因子-1(IGF-1)的反应中,且对转化生长因子-α(TGF-α)反应最为显著。当将绵羊MSC与陶瓷HA/TCP载体联合皮下移植到免疫缺陷小鼠体内时,会导致异位骨生成、脂肪生成和造血支持活性,而将这些细胞移植到明胶海绵内则显示出部分软骨生成。本文所述的绵羊MSC的全面表征为未来涉及绵羊MSC的转化研究提供了重要信息。